Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Establishing Efficacy of an Inpatient Intervention and Phone App to Reduce Suicidal Risk (ASAP+BRITE)
In this 2-site study, University of Texas Southwestern Medical Center (UTSW) and Western
Psychiatric Institute and Clinic (WPIC), the investigators will conduct a randomized clinical
trial (RCT) in 240 psychiatrically hospitalized suicidal adolescents, examining the single
and additive effects of two components of an inpatient unit intervention for suicidal
adolescents, As Safe As Possible (ASAP), which focuses on emotion regulation and safety
planning, and an emotion regulation/safety plan phone app (BRITE).
• Youth admitted to the inpatient unit at either site for a recent suicide attempt or
significant suicidal ideation with a plan or intent.
• The youth and parent are able to complete assessments in English, and the youth is
able to complete therapy.
Exclusion Criteria:
• The youth currently exhibits psychosis.
• The youth currently exhibits mania.
• The youth is currently <85% of their ideal body weight.
• The youth is intellectually incapable of completing the study, e.g. has an
intelligence quotient (IQ) < 70.
Behavioral: ASAP (As Safe As Possible), Behavioral: BRITE smart phone app, Behavioral: TAU (treatment as usual)
Noninvasive Brain Stimulation on Memory in Individuals With Mild Cognitive Impairment and History of Brain Injury
The study will examine the efficacy of high definition transcranial direct current
stimulation (HD-tDCS) and its influence on episodic memory in patients with amnestic mild
cognitive impairment and a history of Traumatic brain injury. Ten sessions of HD-tDCS to the
dorsal anterior cingulate region is expected to result in improvements in episodic memory
measures immediately following the last session and at a 3-month follow-up.
• Age 50 and older
• Native English speakers
• 12 years of education or higher
• Active diagnosis of aMCI
• History of TBI based on VA/DOD criteria
Exclusion Criteria:
• TBI within the past 2 years
• Lifetime history of stroke, transient ischemic attack, heart attack, or congestive
heart failure
• Lifetime history of epilepsy
• Major psychiatric disorders (i.e., posttraumatic stress disorder, bipolar disorder,
schizophrenia)
• Substance use disorder
• Has metal fragments in head
• Taking medications that may interact with the HD-tDCS effect (i.e., amphetamines,
L-dopa, carbamazepine, sulpiride, pergolide, lorazepam, dextromethorphan,
D-cycloserine, flunarizine, or ropinirole)
Device: High Definition Transcranial Direct Current Stimulation, Device: Sham HD-tDCS
Traumatic Brain Injury, Amnestic Mild Cognitive Impairment, Mild Traumatic Brain Injury, Brain and Nervous System
UT Southwestern; Parkland Health & Hospital System
Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents
This project aims to examine the efficacy of ketamine, a rapidly acting medication shown to
decrease suicidality in adults in as short as hours or days, as opposed to weeks.
The study design is a double-blind, randomized, active-control trial of adolescents (ages
13-18 years) with recent suicidal behaviors (suicide attempt or increased suicidal ideation).
All participants must be receiving standard of care treatment which may range broadly from
both outpatient and inpatient programs which include clinically indicated psychosocial and/or
psychopharmacological treatments. Ketamine/midazolam treatment will occur twice weekly during
the first two weeks of the study, followed by weekly assessments through week 12.
Inclusion Criteria
Study participants must:
1. Be adolescents (aged 13-18 years);
2. Have had a recent suicidal event (suicide attempt or significant suicidal ideation
with a plan or intent warranting emergency evaluation or inpatient hospitalization
within the past 30 days);
3. Receiving standard of care treatment that includes clinically indicated psychosocial
and/or psychopharmacological treatment;
4. Have a current primary diagnosis of a depressive disorder based on the MINI-KID (other
psychiatric disorders are acceptable, but must not be primary);
5. Both participants and their designated caregiver must be able to complete assessments
in English, as the rating scales vital to study efficacy and safety evaluations have
not been validated in Spanish. (NOTE: Most potential participants ages 13 to 18 years
old, as well as most of their parents, have a good working knowledge of English);
6. Use effective method of contraception during and for 90 days following the end of
treatment for female and male participants. Recommended methods of birth control are
namely, consistent use of an approved hormonal birth control (pill/patches, rings), an
intrauterine device (IUD), contraceptive injection, double barrier methods, sexual
abstinence, or sterilization;
Exclusion Criteria
Study participants must not:
1. Have lifetime schizophrenia, psychotic disorder, pervasive developmental disorder, or
mental retardation;
2. Have current mania, hypomania, mixed episode, or obsessive-compulsive disorder;
3. Have a primary diagnosis other than a depressive disorder;
4. Have moderate to severe alcohol or substance use disorder within the past six months
(based on MINI-KID); If there is a positive urine drug screen at screening, the urine
drug screen will be repeated at each infusion visit. Positive urine drug screen will
be reviewed by study physician and infusion will proceed as long as no safety risk was
identified;
5. If female, be pregnant, lactating, or nursing; Women of childbearing potential must
have a negative urine pregnancy test prior to all infusions;
6. Have unstable medical conditions (stable for less than 3 months) or with clinically
significant laboratory values or an electrocardiogram (ECG) that would pose
significant risk;
7. Be at serious suicidal risk that cannot be managed in the outpatient setting;
8. Have prior treatment for depression with or contraindications to ketamine, esketamine,
or, midazolam;
9. Treatment with medications that may alter pharmacokinetics of ketamine, including
moderate-to-strong inhibitors or inducers of CYP3A4 and CYP2B6, is exclusionary.
Regarding pharmacodynamic interactions, medications that may increase heart rate or
blood pressure such as the ADHD stimulant medications will be permitted with last dose
at least 24 hours prior to infusion. All concomitant medications will be evaluated by
the study physician to determine if the type and dose of concomitant medication
requires discontinuation and will be excluded if the concomitant medication could
substantially increase the risk of study infusion. A complete list of medications that
are Not Allowed is available in Appendix D of the protocol. The study team will not
ask the participant to discontinue any treatment (except for not taking ADHD
medications for 24 hours before study treatment) just for the sake of taking part in
this study;
10. Weigh >120 kilograms at baseline. If participants are enrolled but exceed 120
kilograms at any time during the treatment period, they will be removed from the
treatment portion of the study.
A Study to Compare the Long-term Outcomes After Two Different Anaesthetics (TREX)
There is considerable evidence that most general anaesthetics modulate brain development in
animal studies. The impact is greater with longer durations of exposure and in younger
animals. There is great controversy over whether or not these animal data are relevant to
human clinical scenarios.
The changes seen in preclinical studies are greatest with GABA agonists and NMDA antagonists
such as volatile anaesthetics (eg sevoflurane), propofol, midazolam, ketamine, and nitrous
oxide. There is less evidence for an effect with opioid (such as remifentanil) or with alpha
2 agonists (such as dexmedetomidine).
Some, but not all, human cohort studies show an association between exposure to anaesthesia
in infancy or early childhood and later changes in cognitive tests, school performance or
risk of developing neurodevelopmental disorders. The evidence is weak due to possible
confounding.
A recent well designed cohort study (the PANDA study) comparing young children that had
hernia repair to their siblings found no evidence for a difference in a range of detailed
neuropsychological tests. In that study most children were exposed to up to two hours of
anaesthesia. The only trial (the GAS trial) has compared children having hernia repair under
regional or general anesthesia and has found no evidence for a difference in neurodevelopment
when tested at two years of age. The GAS and PANDA studies confirm the animal data that short
exposure is unlikely to cause any neurodevelopmental impact.
The impact of longer exposures is still unknown. In humans the strongest evidence for an
association between surgery and poor neurodevelopmental outcome is in infants having major
surgery. However, this is also the group where confounding is most likely.
The aim of our study is to see if a new combination of anaesthetic drugs results in a better
long-term developmental outcome than the current standard of care for children having
anaesthesia expected to last 2 hours or longer.
Children will be randomised to receive either a low dose
sevoflurane/remifentanil/dexmedetomidine or standard dose sevoflurane anaesthetic.
They will receive a neurodevelopmental assessment at 3 years of age to assess global
cognitive function.
• Younger than 2 years (chronological age)
• Scheduled for anaesthesia that is expected to last at least 2 hours (and/or total
operating room time is scheduled to be at least 2.5 hours)
• Has a legally acceptable representative capable of understanding the informed consent
document and providing consent on the participant's behalf.
Exclusion Criteria:
• Known neurologic, chromosomal or congenital anomaly which is likely to be associated
with poor neurobehavioural outcome
• Existing diagnosis of behavioural or neurodevelopmental disability
• Prematurity (defined as < 36 weeks gestational age at birth)
• Birth weight less than 2 kg.
• Congenital cardiac disease requiring surgery
• Intracranial neurosurgery and intracranial craniofacial surgery (isolated cleft lip is
not an exclusion)
• Previous cumulative exposure to general anaesthesia exceeding 2 hours
• Planned future cumulative exposure to anaesthesia exceeding 2 hours before the age of
3 years.
• Any specific contra-indication to any aspect of the protocol
• Previous adverse reaction to any anaesthetic
• Circumstances likely to make long term follow-up impossible
• Living in a household where the primary language spoken at home is not a language in
which we can administer the Wechsler Preschool and Primary School Intelligence Scale
• Planned postoperative sedation with any agent except opioids (e.g. benzodiazepines,
dexmedetomidine, ketamine, barbiturates, propofol, clonidine, chloral hydrate, and
other non-opioid sedatives). For example if such sedation is planned for
post-operative ventilation
Aripiprazole for Bipolar Disorder and Alcohol Use Disorder
The investigators will conduct a 12-week, randomized, double-blind, parallel-group,
placebo-controlled study of aripiprazole in 132 persons with Alcohol Use Disorder (AUD) and
bipolar I or II disorder, currently depressed or mixed phase. Primary Aim will be to assess
change in alcohol use by the Timeline Followback (TLFB) method. Secondary Aim will include
change in alcohol craving using the Penn Alcohol Craving Scale (PACS). Changes in psychiatric
symptoms (mania/hypomania and depression) and predictors of response will be assessed.
Participants with ≥ 1 drinking day at week 12 will be enrolled in a 4-week extension phase
with an upward titration to 30 mg/day for those in the active treatment group. The placebo
group will remain on placebo.
Subjects will be discontinued from the study if any of the following conditions occurs:
change in diagnosis to other than bipolar I or II disorder and AUD, development of active
suicidal or homicidal ideation with plan and intent, worsening in mood symptoms, that in the
opinion of the investigators requires discontinuation, pregnancy, development of severe or
life-threatening medical condition, involuntary psychiatric hospitalization or incarceration,
significant alcohol withdrawal (e.g. delirium tremens) based on clinical judgment (increases
in Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scores will initiate a
careful clinical assessment of possible worsening of withdrawal symptoms), or cocaine or
amphetamine-positive urine drug screen during the study.
• Outpatient men and women age 18-65 years old with bipolar I, II, Not Otherwise
Specified (NOS) disorder, or Schizoaffective Bipolar Type
• If diagnosed with Bipolar I, Bipolar NOS w/history of mania or Schizoaffective
Disorder Bipolar Type, current mood stabilizer therapy (lithium, valproic acid,
lamotrigine, gabapentin) with stable dose for > 28 days prior to randomization.
• Baseline Barrett Impulsiveness Scale-11 Score of > 62 (above average impulsivity)
• Systolic BP > 100 and < 165 and Diastolic BP > 60 and < 105 with no evidence of
orthostatic hypotension
• Current Diagnosis of Alcohol Use Disorder with at least moderate severity
• Alcohol use of an average of 15 drinks per 7 days in the past 28 days prior to intake
for men, and an average of 8 drinks per 7 day period in the past 28 days prior to
intake for women
• Current mood stabilizer therapy with stable dose for > 28 days
• Fluent in English or Spanish
Exclusion Criteria:
• Baseline Hamilton Rating Scale for Depression (HRSD) or Young Mania Rating Scale
(YMRS) scores > 35
• Mood disorders other than bipolar I, II, NOS or schizoaffective disorder bipolar type
(e.g. cyclothymic disorders, schizophrenia, schizoaffective disorder depressive type,
or unipolar depression based on the SCID), other disorders, e.g. anxiety disorders,
will be allowed.
• Current diagnosis of amphetamine or cocaine use disorder or a cocaine or amphetamine
positive baseline urine sample.
• Evidence of clinically significant alcohol withdrawal symptoms
• Current treatment with an atypical antipsychotic
• Current treatment with naltrexone, acamprosate, disulfiram, or topiramate in the last
28 days
• Prior treatment with Aripiprazole within the last year or lifetime history of
intolerable side effects to Aripiprazole
• Vulnerable populations (e.g. pregnant, nursing, cognitively impaired, incarcerated.)
• Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar
score of ≥ 10.
• High risk for suicide
• Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3 times upper
limit of normal
• Current use of Cytochrome P450 3A4 inducing medication (e.g. carbamazepine, rifabutin,
rifampin, ritonavir).
• Use of other substances (besides cocaine/amphetamine) is allowed if the use disorder
is no greater than moderate severity and alcohol is the self-identified substance of
choice.
• History of neuroleptic malignant syndrome or tardive dyskinesia.
More specific inclusion and exclusion criteria will be discussed with participant at
baseline assessment.
A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression
The purpose of this study is to evaluate the efficacy of each individual dose of esketamine
nasal spray, 56 milligram (mg) and 84 mg, compared with placebo nasal spray in improving
depressive symptoms in participants with treatment resistant depression (TRD), as assessed by
the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score
from Day 1 (prerandomization) to the end of the 4 week double-blind treatment phase (Day 28).
• Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (5th
edition) (DSM-5) diagnostic criteria for single-episode MDD or recurrent MDD, without
psychotic features, based upon clinical assessment and confirmed by the MINI.
Participants 65 years of age or older must have had the first onset of depression
prior to 55 years of age
• Participant must have had nonresponse (<=25% improvement) to >=2 oral antidepressant
treatments in the current episode of depression, assessed using the MGH-ATRQ, and
confirmed by documented records (example, medical/pharmacy/prescription records or a
letter from a treating physician)
• Participant must have an Inventory of Depressive Symptomatology-Clinician rated,
30-item (IDS-C30) total score of >=34
• The participant's current major depressive episode, depression symptom severity, and
antidepressant treatment response in the current depressive episode, must be confirmed
by the State vs. Trait, Assessibility, Face Validity, Ecological Validity, Rule of
Three P's (SAFER) Interview
• Participant must be medically stable on the basis of physical examination, medical
history, vital signs (including blood pressure), and 12-lead electrocardiogram (ECG)
performed in the screening phase. If there are any abnormalities that are not
specified in the inclusion and exclusion criteria, the determination of their clinical
significance must be determined by the investigator and recorded in the participant's
source documents and initiated by the investigator
• Participant must be medically stable on the basis of clinical laboratory tests
performed in the screening phase. If the results of the serum chemistry panel,
hematology, or urinalysis are outside the normal reference ranges, the participant may
be included only if the investigator judges the abnormalities or deviations from
normal to be not clinically significant or to be appropriate and reasonable for the
population under study. This determination must be recorded in the participant's
source documents and initialed by the investigator: (a) Participants with a
pre-existing history of thyroid disease/disorder who are treated with thyroid hormones
must be on a stable dosage for 3 months prior to the start of the screening phase; (b)
For any participant (regardless of thyroid history), if the thyroid-stimulating
hormone (TSH) value is out of range, a free thyroxine (FT4) will be conducted. If the
FT4 value is abnormal and considered to be clinically significant (after discussion
with the medical monitor), the participant is not eligible
• Participant must be comfortable with self-administration of nasal spray medication and
be able to follow the nasal spray administration instructions provided
Exclusion Criteria:
• The participant has used ketamine/esketamine (lifetime)
• The participant's depressive symptoms have previously demonstrated nonresponse to an
adequate course of treatment with electroconvulsive therapy (ECT) in the current major
depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
• Participant has received vagal nerve stimulation (VNS) or has received deep brain
stimulation (DBS) in the current episode of depression
• Participant has a current or history of seizures (uncomplicated childhood febrile
seizures with no sequelae are not exclusionary)
• Participant has any anatomical or medical condition that, per the investigator's
clinical judgment based on assessment, may impede delivery or absorption of nasal
spray study drug
Study to Assess the Efficacy and Safety of Adjunctive NBI-1065845 in Adults With Major Depressive Disorder (MDD) (SAVITRI)
The purpose of this study is to evaluate the efficacy of NBI-1065845 compared with placebo
used in addition to oral antidepressants in adults with MDD on improving symptoms of
depression.
Subjects must meet all of these criteria for inclusion in the study:
1. The subject has completed written informed consent.
2. At the time of signing the informed consent, subject must be 18 to 65 years of age,
inclusive.
3. The subject has a primary diagnosis of Major Depressive Disorder (MDD), without
psychotic features, meeting the Diagnostic and Statistical Manual of Mental Disorders,
5th Edition (DSM-5) criteria.
4. Subject must have had inadequate response to antidepressant treatment.
5. Subject is currently on stable pharmacological treatment for depression.
6. Subject must have a total Hamilton Depression Rating Scale-17 Item (HAMD17) score ≥ 22
at screening.
7. Subjects must have been taking current antidepressant medication(s) for ≥ 8 weeks.
8. Subjects must be willing to comply with all study procedures and restrictions.
Exclusion Criteria:
Subjects will be excluded from the study if they meet any of the following criteria:
1. Subject is pregnant or breastfeeding.
2. Subject has an unstable medical condition or chronic disease.
3. Subject has a history of neurological abnormalities.
4. Subject is currently diagnosed with or prior diagnoses of psychiatric disorder which
was the primary focus of treatment other than MDD.
5. The subject's depressive symptoms have previously demonstrated nonresponse to an
adequate course of treatment with electroconvulsive therapy (ECT).
6. The subject has an alcohol or substance use disorder.
7. In the Investigator's opinion, the subject is not capable of adhering to the protocol
requirements.
DHA For The Treatment of Pediatric Concussion Related to Sports Injury
In recent years, media attention has focused on the long-term sequelae of repeated
concussive episodes in professional athletes. The growing understanding of the damage done
by what was once considered a "ding" during a game or match, and the neurologic consequences
of "playing through" or returning to play too soon has led to additional interest in and
concern for pediatric athletes (18 or under) who experience sports-related concussions
during game or practice play.
Because it has only been in recent years that the full scope of damage done by repeated
concussive episodes has come to light, very little research has been done on treatment of
concussion in either adults or children. Brain injuries in children can be especially
problematic, as the brain may continue to develop until the child reaches the age of 24 or
older, so concussion during this time of development may be particularly damaging.
Docosahexaenoic acid (DHA) is an omega-3 fatty acid commonly found in both fish oils and
algae. DHA is known to improve development of the eyes and brain in young children. It is
thought to be an effective anti-inflammatory and anti-oxidant, and since it occurs naturally
and causes very few harmful side effects, it may be a useful compound in the treatment of
pediatric concussion.
This is a feasibility trial of DHA for the treatment of sports concussion in a pediatric
population. The investigators' primary aim is to determine acceptability of randomization
for this compound as well as rate of enrollment given our clinical population. The
investigators' secondary aim is to examine preliminary outcomes. The investigators
hypothesize that subjects who take 2 g of DHA daily for 3 months will see a shorter time to
full recovery and return to play and a shorter time to resolve balance disturbance. These
are good, albeit unvalidated, clinical indicators of concussive recovery.
1. Male or females age 14-18 inclusive
2. Diagnosed with concussion due to sports-related injury. Concussion is defined as:
1. Direct blow to the head, face, neck or a blow elsewhere on the body with an
"impulsive" force transmitted to the head.
2. Rapid onset of short-lived impairment of neurologic function in one or more of
the following clinical domains that resolves spontaneously:
i. Symptoms: somatic (eg, headache), cognitive (eg, feeling like in a fog and/or
emotional symptoms (eg, lability).
ii. Physical signs (eg, loss of consciousness, amnesia).
iii. Behavioral changes (eg, irritability).
iv. Cognitive impairment (eg, slowed reaction times).
v. Sleep disturbance (eg, drowsiness). c) No abnormality on standard structural
neuroimaging studies, if such neuroimaging studies are completed for a
clinically-indicated reason. Note: neuroimaging is not a part of this study protocol.
Study participants will not undergo neuroimaging as part of this study.
3. Concussion within 4 days of enrollment
4. Presenting for treatment to the Sports Medicine Center at Children's Medical Center
Exclusion Criteria:
1. Subjects not actively participating in an organized sport at time of enrollment
2. Subjects who received a concussion from an event other than playing a sport (motor
vehicle accident, fall, etc.)
3. Subjects who participate in or received a concussion during participation in
motorized sports (i.e., motorcross, dirt biking, jet skiing, etc.)
4. Subjects with radiographic evidence of traumatic brain injury (i.e., skull fracture,
intracranial hemorrhage, cerebral contusion, etc).
5. Subjects with a prior diagnosed concussion in the previous 6 months.
6. Pregnant women.
7. Subjects sensitive to aspirin
8. Subjects diagnosed with high blood pressure and currently being treated with blood
pressure medications
9. Subjects allergic to soy bean oil or corn oil.
10. Subjects currently taking fish oil or DHA supplements.
Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST)
This trial aims to assess the efficacy and tolerability of Magnetic Seizure Therapy (MST) as
an alternative to electroconvulsive therapy (ECT) for depression. Even with multiple
medication trials, 30 - 40% of patients will experience a pharmacologically resistant form of
illness. The ineffectiveness of current treatments for major depressive disorder (MDD)
coupled with the economic burden associated with the disorder engenders a need for novel
therapeutic interventions that can provide greater response and remission rates.
Inclusion Criteria
Patients will be included if they:
1. are inpatients or outpatients;
2. are voluntary and competent to consent to treatment and research procedures according
to ECT/MST attending psychiatrist;
3. have a MINI International Neuropsychiatric Interview diagnosis, Version 6 (MINI-6.0)
diagnosis of non-psychotic MDD
4. are 18 years of age or older
5. have a baseline HRSD-24 score > or = 21;
6. are considered to be appropriate to receive convulsive therapy as assessed by an ECT
attending psychiatrist and a consultant anaesthesiologist
7. are agreeable to keeping their current antidepressant treatment constant during the
intervention;
8. are likely able to adhere to the intervention schedule;
9. meet the MST safety criteria [75];
10. If a woman of child-bearing potential: is willing to provide a negative pregnancy test
and agrees not to become pregnant during trial participation.
Exclusion Criteria
Patients will be excluded if they:
1. have a history of MINI diagnosis of substance dependence or abuse within the past
three months;
2. have a concomitant major unstable medical illness;
3. are pregnant or intend to get pregnant during the study;
4. have a MINI diagnosis of any primary psychotic disorder
5. have a MINI diagnosis of obsessive compulsive disorder, or post-traumatic stress
disorder deemed to be primary and causing more functional impairment than the
depressive disorder
6. have probable dementia based on study investigator assessment;
7. have any significant neurological disorder or condition likely to be associated with
increased intracranial pressure or a space occupying brain lesion, e.g., cerebral
aneurysm;
8. present with a medical condition, a medication, or a laboratory abnormality that could
cause a major depressive episode or significant cognitive impairment in the opinion of
the investigator (e.g., hypothyroidism with low TSH, rheumatoid arthritis requiring
high dose prednisone, or Cushing's disease);
9. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear
implants, or electrodes) or any other metal object within or near the head, excluding
the mouth, that cannot be safely removed;
10. require a benzodiazepine with a dose > lorazepam 2 mg/day or equivalent or any
anticonvulsant due to the potential of these medications to limit the efficacy of both
MST and ECT;
11. are unable to communicate in English fluently enough to complete the
neuropsychological tests;
12. have a non-correctable clinically significant sensory impairment (i.e., cannot hear or
see well enough to complete the neuropsychological tests).
Device: Magnetic Seizure Therapy, Device: Electroconvulsive Therapy
Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT)
The researchers are doing the study to see if semaglutide may reduce the risk of having
cardiovascular events in patients with overweight or obesity and with prior cardiovascular
disease. The participant will either get semaglutide (active medicine) or placebo ("dummy"
medicine). Which treatment the participants get is decided by chance. The participant's
chance of getting semaglutide or placebo is the same. The participant will get the study
medicine in a pen. The participants will need to use the pen to inject the study medicine in
a skinfold once a week. The study will last for about 2.5 to 5 years. Participants will have
up to 25 clinic visits with the study doctor.
•Male or female, age greater than or equal to 45 years at the time of
signing informed consent •Body mass index (BMI) greater than or equal to 27 kg/m^2 •Have
established cardiovascular (CV) disease as evidenced by at least one of the following:
prior myocardial infarction; prior stroke (ischemic or haemorrhagic stroke); or symptomatic
peripheral arterial disease (PAD), as evidenced by intermittent claudication with
ankle-brachial index (ABI) less than 0.85 (at rest), or peripheral arterial
revascularization procedure, or amputation due to atherosclerotic disease Exclusion
Criteria: •Any of the following: myocardial infarction, stroke, hospitalisation for
unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the
day of screening •HbA1c greater than or equal to 48 mmol/mol (6.5 %) as measured by the
central laboratory at screening •History of type 1 or type 2 diabetes (history of
gestational diabetes is allowed)
Drug: Semaglutide, Drug: Placebo (semaglutide)
Obesity, Overweight
UT Southwestern; Parkland Health & Hospital System
Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression
Treatment resistant depression remains a major problem for individuals and society. Surgical
procedures may provide relief for some of these patients. The most frequently considered
surgical approach is deep brain stimulation (DBS) of a part of the brain called the
subcallosal cingulate region. However, the effectiveness and safety is not well established.
The investigators will use a novel approach using advanced imaging technique (magnetic
resonance tractography) to evaluate the feasibility and safety of this surgical approach. An
innovative method for the definition of DBS target will be applied that redefines the concept
of targeting as one of targeting a symptomatic network rather than a structural brain region
using subject-based brain anatomy to define the target location. The correlation between
imaging findings at baseline with the mood score changes at different time points of the
study will be investigated.
• Men and women (non-pregnant) between ages 21 and 70;
• DSM-5 diagnosis a current major depressive episode (MDE) for 10 years of less,
recurrent or single episode with first episode after adulthood and did not start
during childhood or adolescence, secondary to nonpsychotic unipolar major depressive
disorder;
• Current index MDE ≥24 months duration and/or recurrent illness with at least a total
of 2 lifetime episodes (including current episode >12 months);
• Treatment resistance (defined by criteria on the Antidepressant Treatment History Form
(ATHF)28): Failure to respond to a minimum of four adequate depression treatments from
different categories;
• Symptom severity for Screening: Hamilton Depression Rating Scale-17 item (HDRS17) ≥20;
• Symptom severity for Outcome: Montgomery Asberg Rating Scale (MADRS) ≥27 to be met at
assessment one week pre-op;
• Normal brain MRI within 3 months of surgery;
• Antidepressant medication regimen has been held stable for ≥ 30 days prior to the
study screening MADRS;
• Remain on stable antidepressant medication throughout the study, unless there are
safety concerns;
• Montreal Cognitive Assessment (MoCA) >25;
• Able and willing to give informed consent and agree to attend regular clinic visits
for at least 12 months.
Exclusion Criteria:
• DSM-5 Axis I Disorders: any lifetime history of psychotic disorder or bipolar
disorder;
• Alcohol or substance use disorder within 6 months, excluding nicotine;
• History of childhood abuse (physical or sexual) 18
• Personality disorders;
• Seeking disability during the trial;
• Current substantial suicidal risk as defined by a plan or clear immediate intent for
self-harm, or made any suicide attempt within the last year; (MADRS ≥ 5 including the
day of surgery);
• No stable work history;
• Neurological/Medical condition that makes the patient, in the opinion of the surgeon,
a poor candidate;
1. Pregnant or has plans to become pregnant in the next 36 months;
2. Unable/unable to practice birth control through the period of randomization and
withdrawal of therapy;
• Subjects who have a history of a seizure disorder;
• Subjects who will be exposed to diathermy;
• Subjects who have any medical contraindications to undergoing DBS surgery (e.g.
infection, coagulopathy, or significant cardiac or other medical risk factors for
surgery);
• Subjects with another implanted device such as a cardiac pacemaker, defibrillator or
neurostimulator;
• Subjects who have a history of hemorrhagic stroke;
• Subjects who are unable to undergo MRI;
• Subjects who are at increased risk of hemorrhage due to underlying medical conditions
or medication.
Device: Abbott Laboratories Infinity™ implantable deep brain stimulation system
Treatment Resistant Depression, Undergoing Deep Brain Stimulation (DBS) Surgery
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating
loss of appetite in patients with cancer that has spread to other places in the body
(advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if
olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and
preventing weight loss.
• Women and men of reproductive potential should agree to use an appropriate method of
birth control throughout their participation in this study due to the teratogenic
potential of the therapy utilized in this trial. Appropriate methods of birth control
include abstinence, oral contraceptives, implantable hormonal contraceptives or double
barrier method (diaphragm plus condom)
• Diagnosis of advanced cancer
• Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or
physician-estimated caloric intake of less than 20 calories/kilogram of body weight
per day
• The patient must perceive loss of appetite and/or weight as a problem; and have an
appetite score of 4 or worse on the "Please rate your appetite…." question that
requires a patient response on a 0-10 numeric rating scale
• Not receiving ongoing tube feedings or parenteral nutrition at the time of
registration
• Not currently using systemic adrenal steroids (with the exception of short-term
dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
• No use of androgens, progesterone analogs, or other appetite stimulants within the
past month
• Patient should not have poorly controlled hypertension or congestive heart failure at
registration
• Patient should not have an obstruction of the alimentary canal, malabsorption, or
intractable vomiting (defined as vomiting more than 3 times per day over the preceding
week)
• Not currently using olanzapine for another medical condition or had previously used
olanzapine for chronic nausea or for any pre-existing psychotic disorder
• Patient should not have had a previous blood clot at any time in the past
• No history of poorly controlled diabetes
• No symptomatic leptomeningeal disease or known brain metastases as these patients may
have difficulty taking oral medications
• No history of hypersensitivity to olanzapine or megestrol acetate
• No COVID-19 infection in the past that, in the opinion of the treating physician, had
left patients with compromised taste, which has not resolved at the time of
registration
• Not pregnant and not nursing, because this study involves an investigational agent
whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn
are unknown. Therefore, for women of childbearing potential only, a negative urine or
serum pregnancy test done =< 14 days prior to registration is required
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Estimated life expectancy of 3 months or longer
• Serum creatinine =< 2.0 mg/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x upper limit
of normal (ULN)
• Fasting glucose > 1410 mg/dl
• Granulocytes > 1000/hpf
• No treatment with another antipsychotic agent, such as risperidone, quetiapine,
clozapine, butyrophenone within 30 days of enrollment
• In order to complete the mandatory patient-completed measures, participants must be
able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking
patients should have access to Spanish speaking staff on site or through the use of a
translation service to be able to conduct the informed consent discussion in Spanish,
and to conduct the weekly phone calls
Exclusion Criteria:
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical condition such as uncontrolled infection (including human immunodeficiency
virus [HIV]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion
of the treating physician, would make this protocol unreasonably hazardous for the
patient
• Patients who cannot swallow oral formulations of the agents
• Patients with impaired decision-making capacity (such as with a diagnosis of dementia
or memory loss) are not eligible for this study
• No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate
cancer (this exclusion criterion is intended to circumvent any confounding
antineoplastic effects of megestrol acetate)
The PATHway Study: Primary Care Based Depression Prevention in Adolescents (PATHway)
Prevention of depressive disorders has become a key priority for the NIMH, but the
investigators have no widely available public health strategy to reduce morbidity and
mortality. To address this need, the investigators developed and evaluated the primary care
based-technology "behavioral vaccine," Competent Adulthood Transition with
Cognitive-Behavioral Humanistic and Interpersonal Therapy (CATCH-IT). The investigators will
engage N=4 health systems representative of the United States health care system, and conduct
a factorial design study to optimize the intervention in preparation for an implementation
study and eventual dissemination.
• Adolescents ages 13 through 18 years, and
• Adolescents must be experiencing an elevated level of depressive symptoms (PHQ-9 =
5-18), and
• Adolescents will be included if they have had past depressive episode/s, but not if
they are in a current depressive episode.
Exclusion Criteria:
1. Outside age range:
1. 12 or younger
2. 19 or older
2. Adolescent is a non-English speaker/reader
3. On the PHQ-9 screening, depression symptom level is:
1. PHQ-9 = 4 or lower
2. PHQ-9 =19 or higher
4. As assessed by the MINI Kid, a current depressive episode
5. As assessed by the MINI Kid, adolescent meets DSM-5 criteria for a psychotic or
bipolar disorder.
6. Currently using medication therapy for depression, anxiety, or other internalizing
disorders.
7. Currently engaged in individual treatment for a mood disorder (assessed by BCC during
phone screen)
8. Currently engaged in a cognitive-behavioral group or therapy (assessed by BCC during
phone screen)
9. Any past psychiatric hospitalizations
10. Any past suicide attempt or incident of self-harm with moderate or greater lethality
11. Extreme, current drug/alcohol abuse (determined by clinician follow up following a
score of 3 or greater on the CRAFFT)
12. Current suicidal thoughts
1. Eligibility will be determined on a case-by-case basis during the baseline PhQ-9
and MINI Kid assessment process and after a consultation with a licensed mental
health clinician has taken place. If adolescent report suicidal ideation on the
baseline PhQ-9, and found ineligible, the MINI Kid assessment may not be
required.
2. Adolescents with current (within the past 6 months), active suicidal feelings
will be excluded.
3. Adolescents with passive thoughts of death or suicide but report to the mental
health clinician that they would never act on these thoughts may be admitted,
depending on the severity of the risk.
4. Adolescents with past (greater than 6 months ago) ideation who are determined to
be low risk will be admitted into the study if there has never been an attempt of
moderate or greater lethality.
13. Significant reading impairment (a minimum sixth-grade reading level based on parental
report) and/or significant intellectual or developmental disabilities
14. Not willing to comply with the study protocol
15. Did not complete phone assessment with MINI Kid by BCC
16. Not affiliated with any of the sites listed in Appendix A.
17. Parent/guardian does not speak English or Spanish
18. Parent/guardian has a cognitive or intellectual impairment
19. Participant Declined/Changed Mind/Uninterested in participating
Behavioral: Competent Adulthood Transition with Cognitive-Behavioral, Humanistic and Interpersonal Training
Depression, Mental Disorder in Adolescence
Adolescents Depression, Internet intervention, Cognitive-Behavioral Therapy, Prevention, MOST design
Elucidating the Neurocircuitry of Irritability With High-Field Neuroimaging to Identify Novel Therapeutic Targets (UNIKET)
The study is investigating dysfunctions in neurocircuitry in regards to irritability with
healthy controls (HC) and individuals with Major Depressive Disorder (MDD) by performing
MRIs. The MDD group will also be randomized to receive ketamine or midazolam to investigate
changes post-treatment in neurocircuitry with regards to irritability.
1. Male or female subjects, 18-65 years of age and body weight less than or equal to 120
kg on baseline visit.
2. Participants must have a level of understanding of the English language sufficient to
agree to all tests and examinations required by the study and must be able to
participate fully in the informed consent process.
3. For Healthy Controls: Subjects must be free of any lifetime psychiatric condition
based on the Mini-International Neuropsychiatric Interview (MINI). For MDD: Subjects
must meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for
current unipolar depression [major depressive disorder (MDD) or persistent depressive
disorder (PDD) in a current major depressive episode (MDE)] based on MINI.
4. A woman of childbearing potential who is sexually active with a male must agree to use
an acceptable method of contraception [defined as either one highly effective
(permanent sterilization, intrauterine device or hormonal implant) or two other forms
of contraception (such as oral contraceptive pill and condom)] to avoid pregnancy
throughout the study. Throughout the study and for 90 days (one spermatogenesis cycle)
after receiving the last dose of study drug (ketamine/midazolam) man who is sexually
active with a woman of childbearing potential must use an acceptable method of
contraception (described above) with his female partner and must agree not to donate
sperm.
5. Subjects must either be free of psychotropic medications (including antidepressants,
antipsychotics, benzodiazepines, mood stabilizers, sedative/hypnotics, dopamine
agonists, stimulants, buspirone, and triptans) and certain anticonvulsants (topiramate
and levetiracetam) or be stable on these medications for four weeks prior to the
baseline visit [first magnetic resonance imaging (MRI) scan].
6. Subjects with MDD should be willing to participate in neuroimaging scans before and
after infusions, and be willing to undergo infusions with study drug.
Exclusion Criteria:
1. Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder,
pervasive developmental disorder or intellectual development disorder.
2. Current diagnosis of obsessive-compulsive disorder, anorexia nervosa or bulimia.
Comorbid anxiety, stress and trauma-related disorders are permitted as long as
unipolar depression is the primary diagnosis.
3. Diagnosis of a moderate or severe substance use disorder within the past 6 months per
MINI; all subjects must have a negative urine toxicology test on the day of the MRI,
prior to the scan.
4. Female subjects who are pregnant, nursing, for may become pregnant. Women of
childbearing potential must have a negative urine pregnancy test on the day of the
fMRI, prior to scan, and on days of study drug infusion, prior to infusion.
5. Any unstable medical illnesses including hepatic, renal, gastroenterologic,
respiratory, cardiovascular (including ischemic heart disease), endocrinologic,
immunologic, or hematologic disease.
6. Inadequately treated obstructive sleep apnea (STOP-Bang score of 5-8 if untreated, if
using positive airway pressure device then past-month apnea hypopnea index ≥ 15 per
hour representing moderate or higher severity).
7. Presence of a significant neurological disease such as Parkinson's disease, primary or
secondary seizure disorders, intracranial tumors, or severe head trauma.
8. Presence of neurocognitive or dementing disorders.
9. Clinically significant abnormalities of laboratories, physical examination (including
unstable hypertension •systolic blood pressure >170, diastolic blood pressure >100),
or electrocardiogram at screening visit.
10. Subjects judged to be at serious and imminent suicidal or homicidal risk by the PI or
another study-affiliated psychiatrist.
11. Any contraindications to MRI, including pacemakers or metallic objects in the body.
12. Any claustrophobia or other conditions which may result in inability to lie still in
the MRI scanner for 1 hour or more.
13. Allergy to ketamine or midazolam in subjects with MDD.
14. Must not be on any prohibited concomitant medication.
Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity (STEP-HFpEF)
This study will look at how the participants daily life is affected by their heart failure.
The study will also look at the change in participants body weight from the start to the end
of the study.
This is to compare the effect on heart failure symptoms and on body weight in people taking
semaglutide (a new medicine) to people taking "dummy" medicine.
Participants will either get semaglutide or "dummy" medicine - which treatment participants
get is decided by chance.
Participants will need to take 1 injection once a week. The study medicine is injected with a
thin needle in a skin fold in the stomach area, thigh or upper arm.
During the study participants will have talks with the study staff about healthy lifestyle
choices including healthy food and physical activity.
The study will last for approximately 59 weeks. Participants will have 11 clinic visits and 1
phone call with the study doctor. Women: Women cannot take part if they are pregnant,
breast-feeding or plan to become pregnant during the study period.
• Male or female, age above or equal to 18 years at the time of signing informed
consent.
• Body mass index (BMI) greater than or equal to 30.0 kg/m^2
• New York Heart Association (NYHA) Class II-IV
• Left ventricular ejection fraction (LVEF) greater than or equal to 45 percentage at
screening
Exclusion Criteria:
• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before
screening irrespective of medical records
• Haemoglobin A1c (HbA1c) greater than or equal to 6.5 percentage (48 mmol/mol) based on
latest available value from medical records, no older than 3 months or if unavailable
a local measurement at screening
A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight (REDEFINE 1)
This study has 2 parts: First part is the main study and second part is the extension study.
During the main study participants will receive 1 of 4 study medicines. If participants
continue in the extension study, they will not receive any study medicine during the
extension. The main study will look at how well CagriSema helps participants with excess body
weight lose weight compared to a "dummy" medicine and 2 other medicines, cagrilintide and
semaglutide. Participants will either get CagriSema, cagrilintide,semaglutide or "dummy"
medicine. Which treatment participants get is decided by chance. They will take one injection
once a week. The study medicine is injected briefly with a thin needle, typically in the
stomach, thighs or upper arms.
Extension study: After the main study, not all participants will continue in the extension
study. The study staff will tell the participant if they will continue or not into the
extension study. In the extension study we will look at what happens to the participant's
body weight and diseases related to excess body weight after the participant stops taking the
study medicine. The main study will last for about 1½ years and the extension study will last
for another 2 years.
• Male or female
• Age above or equal to 18 years at the time of signing informed consent
• Body mass index (BMI) greater than or equal to 30.0 kilograms per square meter
(kg/m^2) or b) BMI greater than or equal to 27.0 kg/m^2 with the presence of at least
one weight-related comorbidity including, but not limited to hypertension,
dyslipidaemia, obstructive sleep apnoea or cardiovascular disease
Exclusion Criteria:
•Glycaemia related: a) Glycated Haemoglobin (HbA1c) greater than or equal to 6.5 percent
(48 millimoles per mole [mmol/mol]) as measured by the central laboratory at screening b)
History of type 1 or type 2 diabetes mellitus
Clinical Medication Development for Bipolar Disorder and Alcohol Use Disorders
Preclinical and clinical data as well as mechanistic justification have been presented
suggesting citicoline and pregnenolone are each promising treatments for alcohol use in BPD.
Both appear to have favorable side effect profiles and no known drug-drug interactions. Thus,
they have the potential to be safely used in a dual diagnosis population already taking other
medications. A 12-week, randomized, double-blind, parallel-group, placebo-controlled adaptive
design study of citicoline and pregnenolone is proposed in 199 persons with alcohol use
disorder and bipolar I or II disorder or schizoaffective disorder (bipolar type). The primary
aim will be to assess change in alcohol use. Biomarkers of alcohol use, alcohol craving, mood
and cognition will also be assessed. Relationships between neurosteroid and choline levels
and the outcome measures will be explored.
• Outpatient men and women age 18-70 years old with bipolar I or II disorder or
schizoaffective disorder (bipolar type)
• English or Spanish speaking
• Current diagnosis of alcohol use disorder with at least moderate severity (DSM-5
terminology)
• Alcohol use of at least an average of 28 drinks a week if male or an average of 21
drinks per week if female and an average of 3 drinking days a week in the 28 days
prior to intake
• Current mood stabilizer therapy (defined as lithium, lamotrigine, carbamazepine,
oxcarbazepine or an atypical antipsychotic) with stable dose for ≥ 28 days prior to
randomization or valproate/divalproex at a stable dose for ≥ 90 days (longer period
due to data suggesting valproate may decrease alcohol use in BPD)
• Diagnosis of substance use disorder other than alcohol, caffeine or nicotine is
allowed if 1) alcohol is the self-identified substance of choice and 2) severity of
other substance use disorder is ≤ moderate
Exclusion Criteria:
• Mood disorders other than bipolar I or II disorders or schizoaffective disorder
bipolar type (e.g. bipolar NOS, cyclothymic disorders, schizophrenia, schizoaffective
disorder depressive type, or unipolar depression based on the SCID); other disorders
(e.g. anxiety, will be allowed)
• Baseline HRSD17 or YMRS scores ≥ 35 to exclude those with very severe mood symptoms at
baseline
• Evidence of clinically significant alcohol withdrawal symptoms defined as a CIWA-Ar
score of ≥ 10
• Current (last 28 days) treatment with naltrexone, acamprosate, disulfiram, or
topiramate as these may also decrease alcohol use
• Oral contraceptives and hormone replacement therapy. This exclusion is due to a
possible interaction with pregnenolone.
• Women with hormone sensitive conditions such as breast cancer, uterine cancer, ovarian
cancer, endometriosis, uterine fibroids. These persons are excluded because
pregnenolone is converted to estrogens.
• Vulnerable populations (e.g. pregnant, nursing, cognitively impaired, incarcerated)
• High risk for suicide defined as > 1 attempt in past 12 months that required medical
attention, any attempt in the past 3 months or current suicidal ideation with plan and
intent such that outpatient care is precluded
• Intensive outpatient treatment (defined as ≥3 visits each week) for substance abuse
(AA, NA meetings, or less intensive counseling at baseline will be allowed)
• Severe/unstable condition (e.g. cirrhosis, poorly controlled hypertension) or
laboratory/physical exam findings consistent with serious illness (e.g. abnormal
electrolytes) or AST or ALT >3 times normal
A Neurosteroid Intervention for Menopausal and Perimenopausal Depression
HYPOTHESIS:
Pregnenolone administration will be associated with greater reduction in depressive symptom
severity than placebo in women with current mMDD.
STUDY AIMS:
Primary Aim: Determine if pregnenolone is associated with greater reduction in depressive
symptom severity than placebo in women with mMDD, as measured by MADRS.
Secondary Aims:
1. Determine if pregnenolone is associated with greater reduction in anxiety symptom
severity than placebo in women with mMDD.
2. Determine if pregnenolone is associated with greater improvement in cognition than
placebo in women with mMDD.
3. Determine if pregnenolone is associated with greater improvement in quality of life than
placebo in women with mMDD.
4. Determine if pregnenolone is associated with greater improvement in vasomotor symptoms
of menopause than placebo.
Mechanistic Aims:
1. Determine whether changes in neurosteroid levels with pregnenolone mediate clinical
response.
2. Determine if baseline neurosteroid levels predict pregnenolone response.
3. Determine whether depressive symptoms, anxiety, sleep or vasomotor symptoms improve
first. A crossed-lagged panel model will explore serial correlations between changes in
outcome measures.
The participants must meet the following criteria:
• Women aged 40-62 years who are perimenopausal or early postmenopausal (within 5 years
of the last menstrual period if not surgically postmenopausal), including:
• Women who have experienced changes in menstrual cycle frequency or duration, and/or
physical symptoms indicative of menopausal transition, as determined by clinician
• Women who are using hormonal IUDs (i.e. brands Mirena and Skyla), with FSH level > 20
mIU/m (as menstrual periods are irregular with IUDs that utilize hormones, making
irregular/absent periods difficult to assess as related to the menopausal transition).
• Women with significant menopause-related physical symptoms, indicated by any of the
following criteria:
• Greene Climacteric Scale total scores > 20
• Greene Climacteric Scale sub-score for vasomotor symptoms >3
• 5 or more bothersome hot flashes per week (self-reported)
• Women meeting DSM-5 criteria for current major depressive disorder (assessed by the
SCID)
• Baseline HRSD score of ≥ 18
• Subject agrees to abstain from disallowed medications for the duration of the trial
Exclusion Criteria:
The participants must not meet any of the following criteria:
• Vulnerable populations (e.g. pregnant/nursing, severe cognitive or intellectual
impairment, incarcerated)
• Pregnancy (determined by urine pregnancy test), intending pregnancy or breast feeding
• Psychiatric disorder other than MDD that is acute and the primary focus of symptom
burden or treatment.
• History of bipolar disorder or psychotic disorder
• Current substance use disorder
• Positive baseline urine drug screen of an illicit substance (in this study: opioids
and cocaine,) with the exception of a medication used with a prescription (use of a
detected substance that is used with a prescription, such as an opioid pain
medication, is not necessarily exclusionary and will be based upon judgment of the PI,
particularly in the cases of chronic opioid use). Participants who screen positive for
marijuana will be offered a rescreen for eligibility at a later date.
• Current eating disorder
• Treatment resistant depression (failure of 2 adequate antidepressant trials or
electroconvulsive therapy (ECT) during current episode; adequate antidepressant trials
are defined as within the US FDA approved dosage for the medication and used for at
least 6 weeks, with failure described by the patient as <50% improvement based on her
subjective experience).
• High risk for suicidal acts including active suicidal ideation with plan and intent or
> 2 suicide attempts in lifetime or any attempt in the past 6 months
• Use of selective estrogen-receptor modulators (SERMs), hormone replacement therapy,
hormonal contraceptives (hormonal IUDs allowed), episodic sleep medications (chronic,
regular, stable-dose benzodiazepines and hypnotics such as zolpidem, Sonata
(Zaleplon), and Lunesta (Eszopiclone) OR sleep-seating antihistamines such as Unisom
(Doxylamine succinate) or diphenhydramine allowed) within 2 weeks of the baseline
visit and randomization. Antidepressants will be allowed for those participants who
have been taking the antidepressant for 6 weeks with a stable dose for at least 4
weeks.
• Use of natural menopause and depression supplements, phytoestrogens, soy-based
medications, steroids within 2 weeks of baseline visit and randomization.
• Use of any disallowed medications (specified in the Excluded Concomitant Medication
section below).
• Women who have received a gonadal hormonal intervention within 1 month prior to study
entry (stable thyroid medications are allowed).
• Not using a medically approved method of birth control, if sexually active and not 12
or more months since last menstrual period IUDs, condoms, abstinence are acceptable
forms of contraception in this study; due to the possible interactions with the study
medication, oral contraceptive pills will be prohibited.
• Uncontrolled hypertension (>160/95mmHg)
• Active coronary artery disease, atrial fibrillation, stroke, deep vein thrombosis,
pulmonary embolism or blood clotting disorder
• Any severe, life threatening or unstable medical condition that, based on
clinician-judgment, would make participation in the study unsafe or inappropriate
• Personal or first degree family history of known hormone sensitive tumors
• History of allergic reaction or side effects with prior pregnenolone use
• Clinically significant laboratory or physical examination findings
• Concurrent enrollment in another clinical trial
Exclusion of Concomitant Medications:
• Selective estrogen-receptor modulators (SERMs)
• Hormone replacement therapy
• Hormonal contraceptives, excluding Mirena IUD or other IUD with localized progesterone
• Natural menopause or antidepressant supplements
• Episodic sleep medications (chronic, regular, stable-dose benzodiazepines and
hypnotics such as zolpidem, Sonata (Zaleplon), and Lunesta (Eszopiclone) OR
sleep-sedating antihistamines such as Unisom (Doxylamine succinate) or diphenhydramine
allowed)
• Sub-therapeutic dosages of antidepressants used for other indications will be
permissible with the exclusion of SSRIs, SNRIs, and Wellbutrin.
• Phytoestrogens
• Soy-based medications or supplements
Drug: Pregnenolone, Drug: Placebo
Major Depressive Disorder, Menopause, Perimenopause
Exploring the Effects of Corticosteroids on the Human Hippocampus
Chronic corticosteroid (CS) exposure is associated with changes in memory and the hippocampus
in both humans and in animal models. The hippocampus has a high concentration of
glucocorticoid receptors (GCRs), and the pre-clinical literature demonstrates shortening of
apical dendrites in the CA3 region of the hippocampus and decreased neurogenesis in the
dentate gyrus (DG) following CS administration. In humans, both stress and CS exposure are
associated with a decline in declarative memory performance (a process mediated by the
hippocampus). Impairment in declarative memory and hippocampal atrophy are reported in
patients with excessive CS release due to Cushing's disease, and, by our group, in patients
receiving prescription CS therapy. These findings have important implications for patients
with mood disorders, as a large subset of people with major depressive disorder (MDD) show
evidence of HPA axis activation, elevated cortisol and, importantly, resistance to the
effects of CSs on both the HPA axis and on declarative memory. Thus, resistance to
corticosteroids appears to be a consequence of MDD.
this study will examine changes in declarative memory, as well as use state-of-the-art
high-resolution multimodal neuroimaging, including structural and functional (i.e.,
task-based and resting state) MRI, in both men and women healthy controls, and, as an
exploratory aim, a depressed group, given 3-day exposures to hydrocortisone (160 mg/day) or
placebo. The study will translate preclinical findings to humans, provide valuable data on
possible sex differences in the response to cortisol and, for the first time, identify
specific hippocampal subfields (e.g., CA3/DG) in humans that are most sensitive to acute CS
effects. Using resting state fMRI data and whole brain connectomics using graph theoretical
approaches, we will determine the effects of cortisol exposure on functional brain networks.
Furthermore, this will be the first study to use neuroimaging to compare the brain's response
to CSs in people with depression vs. controls, and determine whether depressed people
demonstrate glucocorticoid resistance within the hippocampus. We hypothesize that hippocampal
response to acute CSs will be greatest in the CA3/DG subfield, greater in women than in men,
and that depressed people will show a blunted hippocampal response to CSs compared to
controls. A multidisciplinary research team with extensive experience in CS effects on the
brain and hippocampal subfield neuroimaging, and a prior history of research collaboration,
will conduct the project.
• Men and women age 18-40 years with vision corrected to at least 20-40 (needed for fMRI
tasks)
• Education of ≥ 12 years
• Baseline RAVLT total words recalled T-score ≥ 40 (normal range)
• BMI between 18.5-35.0 (neither underweight nor severely obese)
• Baseline QIDS-C ≤ 5 (virtual absence of depressive symptoms) for "healthy controls"
and for the "depressed" group a QIDS-C between 11-20 (≥ moderate depressive symptoms
but < very severe depressive symptoms)
Exclusion Criteria:
• History of major psychiatric illness other than MDD for the depressed group, defined
as bipolar disorder, posttraumatic stress disorder, schizoaffective disorder,
schizophrenia, eating disorders, or MDD with psychotic features. For the control
group, a past episode of MDD (per SCID) is also exclusionary
• History of drug or alcohol use disorder
• History of neurological disorders including seizures, brain surgery, multiple
sclerosis, Parkinson's disease
• Taking CNS-acting medications (e.g., antidepressants, antipsychotics, lithium,
anticonvulsants, sedative/hypnotic/anxiolytics). Thus, the depressed group will be
medication free.
• History of allergic reaction or medical contraindication to hydrocortisone
• Metal implants, claustrophobia, or other contraindications to MRI
• Significant medical conditions (e.g., cancer, heart disease, diabetes)
• Vulnerable population including pregnant or nursing women, prisoners, and people with
intellectual disability, history of special education classes, dementia, or other
severe cognitive disorders
• Current suicidal ideation, a suicide attempt in the past 12 months or more than one
lifetime attempt
• History of systemic CS use in the past 12 months, lifetime cumulative use of more than
12 weeks, or recent (defined as past 28 days) inhaled CS use
• Women who are using estrogen containing oral contraceptive agents (other
contraceptives are acceptable, see Protection of Human Subjects section for a list of
acceptable birth control methods) or who are post- or peri-menopausal or with
irregular menstrual cycles (i.e., inconsistent menstruation patterns)
Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)
The overall goal of the study is to determine if treatment of a Major Depressive Disorder
(MDD) improves the outcomes of patients with chronic kidney disease (CKD). We showed that MDD
is present in 25% of CKD patients and independently associated with progression to End-Stage
Kidney Disease, hospitalization, and death. Depression is also associated with lower quality
of life (QOL), fatigue, poor sleep, and non-adherence to diet and medications. However,
evidence for efficacy and tolerability of commonly-used antidepressant medications or
nonpharmacologic treatments are limited in CKD patients. Our group was the first to conduct a
double-blind randomized controlled trial for MDD treatment in 201 patients with non-dialysis
CKD, and showed that sertraline, a commonly used selective serotonin reuptake inhibitor
(SSRI), was no more efficacious than placebo for improving depressive symptoms. It becomes
imperative to test novel strategies to treat MDD in CKD. We propose to compare with a control
group, the efficacy and tolerability of two novel treatment strategies - (1) Behavioral
Activation Teletherapy (BAT) for 16 weeks, with the addition of bupropion, a non-SSRI
antidepressant, at 8 weeks for patients whose depression has not remitted (non-remitters);
and (2) bupropion for 16 weeks, with the addition of BAT at 8 weeks for non-remitters. In Aim
1, we will investigate the efficacy and tolerability of these 2 strategies vs. control for
improvement in a primary endpoint of depressive symptoms in 201 patients (67 per group) with
non-dialysis CKD stages 3b-5 and MDD at 2 sites, randomized 1:1:1 to either strategy or a
control group of Clinical Management plus placebo. We hypothesize that either approach vs.
control will result in a minimal clinically important difference of 2 points improvement in
depressive symptoms, as ascertained blindly by the Quick Inventory of Depressive
Symptomatology. In Aim 2 we will investigate the efficacy and tolerability of 8 weeks of (1)
single-blind BAT plus placebo or (2) double-blind bupropion plus Clinical Management vs.
control for improvement in depressive symptoms. In Aim 3, we will compare the efficacy of
these 2 treatments strategies vs. control for improvement in CKD patient-centered outcomes
including a. adherence to medications and healthcare visits; b. fatigue; c. sleep; and d.
overall functioning. A clinical trial is urgently needed to address the evidence gap that
exists for MDD treatment in CKD patients.
1. Male or female adults aged 18 years or greater. There will be no upper age limit.
2. Presence of CKD stages 3b, 4 or non-dialysis stage 5, with an estimated glomerular
filtration rate (GFR) of <45 mL/min/1.73 m2 for a period of at least 3 months, as
defined by the National Kidney Foundation and determined using the four-variable
Modification of Diet for Renal Diseases Study formula.
3. Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based
criteria
4. Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at
enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization.
5. Able to understand and sign informed consent after the nature of the study has been
fully explained
Exclusion Criteria:
1. Unable to understand or give informed consent.
2. Unwilling or unable to participate in the protocol or comply with any of its
components
3. Receiving chronic dialysis
4. Kidney transplant recipient
5. Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than
the upper limit of normal
6. Terminal chronic obstructive pulmonary disease or cancer
7. Presence of seizure disorder
8. Current use of class I anti-arrhythmic medications (such as 1C propafenone and
flecanide), pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine, or
methyldopa; tri-cyclic anti-depressants, neuroleptics, or anti-convulsants
9. Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid,
tryptophan, and St. John's Wort.
10. Use of medications known to cause QT prolongation on EKG
11. Ongoing use of antidepressant medications for depression treatment
12. Past treatment failure on bupropion
13. Initiation of depression-focused psychotherapy in the 3 months prior to study entry
14. Active alcohol or substance abuse or dependence that requires acute detoxification at
study entry
15. Present or past psychosis or Bipolar I or II disorder
16. Dementia or a Mini-Mental State Examination score <23
17. Active suicidal intent
18. Pregnancy, lactation, or women of childbearing potential not willing to use adequate
contraception
Antipsychotic Response to Clozapine in B-SNIP Biotype-1 (Clozapine)
The CLOZAPINE study is designed as a multisite study across 5 sites and is a clinical trial,
involving human participants who are prospectively assigned to an intervention. The study
will utilize a stringent randomized, double-blinded, parallel group clinical trial design. B2
group will serve as psychosis control with risperidone as medication control. The study is
designed to evaluate effect of clozapine on the B1 participants, and the effect that will be
evaluated is a biomedical outcome. The study sample will be comprised of individuals with
psychosis, including 1) schizophrenia, 2) schizoaffective disorder and 3) psychotic bipolar I
disorder. The investigators plan to initially screen and recruit n=524 (from both the
existing B-SNIP library and newly-identified psychosis cases, ~50% each) in order to enroll
n=320 (B1 and B2) into the RCT.
• 18-50y/o; males and females; all races and ethnicities; able to provide written
informed consent; able to read, speak, and understand English; medically stable;
meeting DSM-IV (SCID-based) criteria for schizophrenia, schizoaffective disorder, or
bipolar I disorder with psychotic features (we will use DSM-IV to be consistent with
prior B-SNIP samples); PANSS total score of ≥70 and at least one item scored ≥5 or two
items scored ≥4 on PANSS Positive Subscale; normal baseline values for absolute
neutrophil count (ANC above 1500/mm3)
Exclusion Criteria:
• premorbid intellectual ability estimate below 70 (WRAT-4, Word Reading subtest,
age-corrected standardized score); comorbid DSM-IV diagnosis of alcohol or substance
abuse in prior 1 month or substance dependence in prior 3 months; neurological (e.g.,
seizure disorder, stroke, traumatic brain injury with a loss of consciousness ≥ 30min)
or severe medical condition (e.g., decompensated cardiovascular disorder, AIDS) that
may affect central nervous system function; concomitant medications known to affect
EEG properties (i.e., lithium, anticonvulsants, benzodiazepines) or strong CYP 1A2
inhibitors (e.g., ciprofloxacin, enoxacin) or strong CYP 3A4 inducers (e.g.,
phenytoin, carbamazepine, phenobarbital, rifampin) which cannot be safely
discontinued; vulnerable populations (e.g., pregnant, nursing, incarcerated);
unwilling to use reliable means of contraception; history of neuroleptic malignant
syndrome; prior treatment with clozapine, prior treatment with long-acting injectable
antipsychotics that are 1-month formulations within the past 3 months and for 3-month
formulations within the past 6 months; intolerable side effects to either clozapine or
risperidone in lifetime, or a previously failed trial of either clozapine or
risperidone at adequate doses in lifetime; history of drug reaction with eosinophilia
and systemic symptoms syndrome (DRESS), also known as drug-induced hypersensitivity
syndrome (DIHS); high risk for suicide defined as more than 1 attempt in past 12
months that required medical attention, any attempt in the past 3 months or current
suicidal ideation with plan and intent such that outpatient care is precluded; current
homicidal ideation with plan and intent such that outpatient care is precluded.
Drug: clozapine, Drug: risperidone
Schizophrenia, Schizoaffective Disorder, Brain and Nervous System, Bipolar 1 Disorder
Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study) (IPAT)
The purpose of this study is to determine if intensive lowering of systolic blood pressure
(SBP), using FDA approved medications (antihypertensive), reduces Alzheimer's Disease
pathology (i.e., excessive brain amyloid and tau protein deposition) in older adults at high
risk for memory decline or dementia.
• Age 60-80, all races/ethnicities, and both sexes are eligible;
• a) A positive family history of dementia defined as having at least one first-degree
relative with a history of AD or other type of dementia or
• b) having subjective memory complaints defined as a positive answer to BOTH of the
following questions:
1. "Are you worried about your memory or thinking abilities?
a) Not at all, b) A little bit, c) A lot"; B and C •includes
2. "Do you feel you have difficulty with your memory or thinking that is worse than
in the past?" b) Yes or No; Yes •includes
• Mini-Mental State Exam (MMSE) ≥ 26 to exclude gross dementia; based on clinical
judgment, may be rescreened in ≥ 7 days;
• Individuals with SBP ≥ 130 and SBP ≤ 180; Those on antihypertensives are eligible. If
an individual, not treated for HTN, has a SBP ≥ 125 mmHg, consider rescreening after
24 hours;
• Willingness to be randomized into the treatment groups and ability to return to clinic
for follow-up visits over 24 months;
• Fluency in English or Spanish or both, adequate visual and auditory acuity to allow
neuropsychological testing;
• Participants must have a regular healthcare provider.
Exclusion Criteria:
• Clinically documented history of stroke, focal neurological signs or other major
cerebrovascular diseases based on clinical judgment or MRI/CT scans such as evidence
of infection, infarction, or other brain lesions;
• Diagnosis of AD or other type of dementia, or significant neurologic diseases such as
Parkinson's disease, seizure disorder, multiple sclerosis, history of severe head
trauma or normal pressure hydrocephalus;
• Evidence of severe major depression (GDS ≥ 12, may be rescreened after 12 weeks or
longer if evidence of reactive depression or temporary mood disturbances) or
clinically significant psychopathology, (e.g., psychosis and schizophrenia); if
hospitalized in past year, can be rescreened in 6 months; or presence of a major
psychiatric disorder that in the investigator's opinion, could interfere with
adherence to research assessments or procedures.
• Unstable heart disease based on clinical judgment (e.g., heart attack/cardiac arrest,
cardiac bypass procedures within previous 6 months and congestive heart failure), or
other severe medical conditions;
• History of atrial fibrillation and evidence on ECG with any of the following: active
symptoms of persistent palpitation, dizziness, history of syncope, chest pain,
dyspnea, orthopnea, shortness of breath at rest, or paroxysmal nocturnal dyspnea
within the past 6 months; resting heart rate of < 30 or > 110 bpm; taking class I or
III antiarrhythmic drugs including flecainide, propafenone, dronedarone, sotalol,
dofetilide, and amiodarone; or clinical concerns for safely participating in lowering
blood pressure.
• Systolic BP equal or greater than 180 mmHg and/or diastolic BP equal or greater than
110 mmHg, may be rescreened in 1 week.
• Orthostatic hypotension, defined as the third standing SBP < 100mmHg, may be
rescreened after 2 weeks;
• History of significant autoimmune disorders such as systemic lupus erythematosus,
rheumatoid arthritis or polymyalgia rheumatica;
• Significant history of alcoholism or drug abuse within the last five years;
• Uncontrolled diabetes mellitus, defined as hemoglobin A1C > 6.5%, or requiring insulin
treatment;
• Clinically diagnosed and untreated sleep apnea;
• Regularly smoking cigarettes within the past year;
• Pacemaker or other medical device of metal that precludes performing MRI;
• Women with a potential for pregnancy, lactation/childbearing (2 year post-menopausal
or surgically sterile to be considered not childbearing potential);
• Participant enrolled in another investigational drug or device study, either currently
or within the past 2 months;
• Severe obesity with BMI > 40 ; clinical judgment should be applied in all cases to
assess patient safety and anticipated compliance;
• Allergy to angiotensin receptor blockers (ARBs), i.e., drugs that have a suffix
"-sartan"; allergy to amlodipine;
• Abnormal screening laboratory tests (e.g., liver ALT and AST > 3 x ULN, GFR < 30 or
Hct < 28%); may be rescreened after 2 weeks or longer;
• A medical condition likely to limit survival to less than 3 years;
• Participant has any condition(s) judged by the study investigator to be medically
inappropriate, risky or likely to cause poor study compliance. For example:
1. Plans to move outside the clinic catchment area in the next 2 years;
2. Significant concerns about participation in the study from spouse, significant
other, or family members;
3. Lack of support from primary health care provider;
4. Residence too far from the study clinic site such that transportation is a
barrier including persons who require transportation assistance provided by the
study clinic funds for screening or randomization visits;
5. Residence in a nursing home; persons residing in an assisted living or retirement
community are eligible if they meet the other criteria;
6. Other medical, psychiatric, or behavioral factors that, in the judgment of the
site PI or clinician, may interfere with study participation or the ability to
follow the study Protocol.
7. Couples or significant partners who live together cannot be enrolled or
participate simultaneously in the study.
Drug: Angiotensin II Receptor Blockers (ARBs, losartan) and Calcium Channel Blockers (CCB, amlodipine), Other: PCP
Hypertension, Cognitively Normal Older Adults, Subjective Cognitive Decline, Brain and Nervous System, Family History of Dementia
Dementia, Alzheimer's Disease, Cognitive Function, Blood Pressure, Amyloid, Tau
Study to Evaluate the Efficacy and Safety of Once-Weekly Oral NBI-1065846 in the Treatment of Anhedonia in MDD (TERPSIS)
To evaluate the efficacy of NBI-1065846, used as adjunctive treatment to oral antidepressant
medication(s), compared with placebo on improving symptoms of anhedonia in subjects with
major depressive disorder (MDD).
Subjects must meet all of the following key inclusion criteria:
1. Completed written informed consent.
2. Aged 18 to 65 years, inclusive, at the time of informed consent.
3. Diagnosis of MDD meeting the Diagnostic and Statistical Manual of Mental Disorders,
5th Edition (DSM-5) and International Statistical Classification of Diseases and
Related Health Problems, 10th Revision (ICD-10).
4. Subject is currently on stable pharmacological treatment for depression, defined as
≤50% change in dose during the 6 weeks prior to randomization to ≥1 of the oral
antidepressant medications listed in the MGH ATRQ.
5. Snaith Hamilton Pleasure Scale (SHAPS) score is ≥30 at screening and Day 1.
Key
Exclusion Criteria:
Subjects will be excluded from the study if they meet any of the following key criteria:
1. Any psychiatric disorder disallowed per protocol and electroconvulsive therapy (ECT)
within 6 months prior to screening. Comorbid anxiety disorders are not exclusionary.
2. Have a significant risk of suicidal or violent behavior. Subjects with any suicidal
ideation of type 4 (active suicidal ideation with some intent to act, without specific
plan) or type 5 (active suicidal ideation with specific plan and intent) in the past
12 months before screening based on the C-SSRS or according to the investigator's
clinical judgment should be excluded.
3. A history of seizure disorder, stroke, Alzheimer disease, Parkinson disease, multiple
sclerosis, head injury associated with loss of consciousness for more than 15 minutes,
or other neurodegenerative disorder.
Drug: Placebo, Drug: NBI-1065846
Major Depressive Disorder, Anhedonia
Anhedonia, Major Depressive Disorder, MDD, NBI-1065846, TERPSIS, Neurocrine, Antidepressant, Depression
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER)
Objectives of this study are to determine whether active VNS Therapy treatment is superior to
a no stimulation control in producing a reduction in baseline depressive symptom severity,
based on multiple depression scale assessment tools at 12 months from randomization.
The patient must be in a major depressive disorder (MDD) episode for ≥ two years or have
had at least four episodes of MDD, including the current episode.
The patient's depressive illness meets a minimum criterion of four prior failed treatments
of adequate dose and duration as measured by a tool designed for this purpose.
The patient is experiencing a major depressive episode (MDE) as measured by a guideline
recommended depression scale assessment tool on two visits, within a 45-day span prior to
implantation of the VNS device.
Patients must maintain a stable medication regimen for at least four weeks before device
implantation.
Exclusion Criteria:
Current or lifetime history of psychotic features in any MDE;
Current or lifetime history of schizophrenia or schizoaffective disorder;
Current or lifetime history of any other psychotic disorder;
Current or lifetime history of rapid cycling bipolar disorder;
Current secondary diagnosis of delirium, dementia, amnesia, or other cognitive disorder;
Current suicidal intent; or
Treatment with another investigational device or investigational drugs.
Device: Vagus Nerve Stimulation (VNS)
Treatment Resistant Depression, Brain and Nervous System
Research Study Looking at How Well Semaglutide Tablets Taken Once Daily Work in People Who Have a Body Weight Above the Healthy Range (OASIS 4)
This study will look how well semaglutide tablets taken once daily helps people with body
weight above the healthy range. Participants will either get semaglutide 25 milligram (mg)
once daily or placebo once daily. This study will last for 72 weeks, which includes 1-week
screening period, 64 weeks of treatment period and 7 weeks of follow up period.
• Informed consent obtained before any study-related activities. Study-related
activities are any procedures that are carried out as part of the study, including
activities to determine suitability for the study
• Male or female, age greater than or equal to 18 years at the time of signing informed
consent
• Body mass index (BMI) of
• Greater than or equal to 27.0 kg/m^2 with the presence of at least one of the
following weight-related complications (treated or untreated): hypertension,
dyslipidaemia, obstructive sleep apnoea or cardiovascular (CV) disease OR
• Greater than or equal to 30.0 kg/m^2
• History of at least one self-reported unsuccessful dietary effort to lose body weight
Exclusion Criteria:
• A self-reported change in body weight greater than 5 kg (11 pound [lbs]) within 90
days before screening irrespective of medical records
• HbA1c greater than or equal to 6.5 percent (48 mmol/mol) as measured by the central
laboratory at screening
Dallas 2K: A Natural History Study of Depression (D2K)
The Dallas 2K is a 10-year natural history, longitudinal, prospective study of a cohort of
2,000 participants that will help uncover the socio-demographic, lifestyle, clinical,
psychological and neurobiological factors that contribute to anti-depressant treatment
response: remission, recurrence, relapse and individual outcomes in depressive disorders.
Hence, the expected duration of this study is 20 years in length. Since this is an
observational study, investigators will explore a comprehensive panel of carefully selected
participant specific parameters: socio-demographic (age, ethnicity, economic); lifestyle
(physical activity, substance use); clinical (medical history, anxious depression, early life
trauma), biological (biomarkers in blood, saliva, urine), behavioral (cognitive, emotional),
neurophysiological (EEG), and neuroimaging (structural, functional brain circuitry) with the
goal to develop the most robust predictive models of treatment response and of depression
outcomes. There is no medication or non-medication treatment or intervention provided by this
study.
Subjects will have elevated symptomatology of nonpsychotic chronic or recurrent depressive
disorder and will be currently receiving or will be prescribed standard of care medication or
non-medication based treatments by their providers/clinicians. The study cohort will reflect
the wide range of patients seen in typical primary or psychiatric care settings, and may
include unipolar or bipolar disorders and dysthymia (a more chronic form of depression). The
cohort will be broadly representative of and generalizable to the US general population as a
whole.
Criteria for Inclusion of participants:
A potential participant will be eligible for participation in this study if the following
criteria are met:
1. Male and female adult or youth aged 10 and older of any race or ethnicity.
2. Ability to speak, read, and understand English. However, the parent(s) or legal
guardians of minors may either speak English or Spanish as the consenting process can
be conducted bilingually.
3. A lifetime or a current diagnosis of a mood disorder based upon a semi-structured
diagnostic interview.
4. Adults age 18 and older must be able to provide written informed consent; for youth
younger than age 18, a parent or legal guardian must provide written informed consent,
and the child or teen must provide written informed assent.
Eligibility for Healthy Controls
For comparison purposes, potential health control participants who do NOT have a
psychiatric diagnosis will be enrolled as part of the healthy control arm of this study.
1. Male and female adult or youth aged 10 and older of any race or ethnicity.
2. Ability to speak, read, and understand English. However, the parent(s) or legal
guardians of minors may either speak English or Spanish as the consenting process can
be conducted bilingually.
3. Adults age 18 and older must be able to provide written informed consent; for youth
younger than age 18, a parent or legal guardian must provide written informed consent,
and the child or teen must provide written informed assent.
Criteria for Exclusion of Participants
A potential participant will NOT be eligible for participation in this study if any of the
following criteria are met:
1. History of schizophrenia, schizoaffective disorders or chronic psychotic disorders
based upon a semi-structured diagnostic interview.
2. Diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C (human
immunodeficiency virus (HIV) testing is not required for this study).
3. Unable to provide a stable home address and contact information.
4. Has any condition for which, in the opinion of the investigator or designee, study
participation would not be in their best interest (including but not limited to
cognitive impairment, unstable general medical condition, intoxication, active
psychosis) or that could prevent, limit, or confound the protocol-specified
assessments.
5. Requires immediate hospitalization for psychiatric disorder or suicidal risk as
assessed by a licensed study clinician.
Eligibility for Healthy Controls
A potential Healthy Control participant will NOT be eligible for participation in this
study if any of the following criteria are met:
1. A lifetime or a current history of a mood disorder based upon a semi-structured
diagnostic interview.
2. Meets any exclusion criteria as part of the main D2K study interview.
Other: Observational Study
Depression, Depression, Bipolar
UT Southwestern; Children’s Health; Parkland Health & Hospital System
Mapping the Phenotype in Adults With Phelan-McDermid Syndrome
The protocol aims to comprehensively define the phenotype of Phelan-McDermid Syndrome and to
identify potential genetic factors, which may play a role in the variability of the disease's
outcomes. The first aim involves a physical exam, a neurological exam, collection of medical
history information, a clinical genetic evaluation, blood work and neuropsychological
assessments. If clinically indicated, the protocol collects information from medical tests.
These medical tests may include electrocardiography, echocardiography, renal ultrasonography,
and renal ultrasound.
• Participant is 22 years of age and older at the time of enrollment
• Participant has been diagnosed with pathogenic deletions or mutations of the SHANK3
gene
• Participant is proficient in English
• Participant provided consent
Patients undergoing open total abdominal hysterectomy (n=82) at Parkland Memorial Hospital
will be randomized into one of two groups to receive either ultrasound-guided bilateral ESP
block with liposomal bupivacaine (Group 1) or ultrasound-guided bilateral QL block with
liposomal bupivacaine (Group 2) for postoperative pain management. The remaining aspect of
perioperative care, including the general anesthetic technique and postoperative care will be
standardized and will be similar for all patients. The duration of the involvement in the
study will be until 72 hours postoperatively. Anesthesia providers will identify potential
subjects during their Pre-Anesthesia Evaluation Clinic visit and/or Day Surgery Unit
pre-anesthetic assessment. There will be no incentive or payment to the patients.
Patients in Group 1 will receive ultrasound-guided bilateral ESP block in the preoperative
holding area prior to surgery. Patients in Group 2 will receive ultrasound-guided QL block in
the preoperative holding area prior to surgery. All patients will have general anesthesia per
previously established Parkland Enhanced Recovery After Surgery (ERAS) protocols.
Postoperatively, patients in both Groups will receive acetaminophen 1000 mg orally every 8
hours, meloxicam 15 mg orally every 24 hours, and immediate-release oxycodone 5 - 10mg orally
every 4 hours as needed for breakthrough pain.
The postoperative analgesia will be documented using the Numeric Rating Scale (0-10 scale
where 0=no pain and 10=worst pain). In addition, total opioid dose over the 72-hours study
period will be documented. Postoperative nausea will be measured using a categorical scoring
system (none=0, mild=1, moderate=2, severe=3) and episodes of vomiting will be documented.
Rescue anti-emetics will be given to any patient who complains of nausea and/or vomiting. All
variables will be assessed at 4, 6, 12, 24, 48, and 72 hours, postoperatively by an
investigator blinded to group allocation.
• Female ASA physical status 1-3 scheduled for open abdominal hysterectomy
• Age 18-80 years old
• Able to participate personally or by legal representative in informed consent in
English or Spanish
Exclusion Criteria:
• History of relevant drug allergy
• Age less than 18 or greater than 80 years
• Chronic opioid use or drug abuse
• Active use of anticoagulant medication
• Significant psychiatric disturbance
• Inability to understand the study protocol
• Refusal to provide written consent
Characterizing Inflammatory Profiles and Suicidal Behavior in Adolescents
Despite increasing suicide rates in adolescents, there remains a paucity of approaches to use
to prevent re-attempts. Any hope for breaking the code to prevent youth suicide lies in
understanding biological factors that play a role. Evidence suggests that inflammation and
immune system dysfunction may be linked to suicide. The investigators will develop immune
profiles for adolescents with suicidal behavior and those at risk in order to develop tools
that can be implemented for prevention efforts.
This study involves blood draws, answering questions, and completing questionnaires - no
treatment or intervention is provided as part of this study. Participants will be screened to
see if they qualify for this study using questionnaires.
Participants will be teens (ages 12-18 years) with recent suicidal behavior, teens at-risk
for developing depression, and healthy control teens. Participants complete all study-related
tasks four times over a period of 12 months. Electronic surveys will be sent to participants
to complete monthly. Both the adolescent and if applicable, their parent (or legally
authorized representatives, LARs), will answer questions regarding depression, anxiety, and
suicidal thoughts/behaviors.
Inclusion Criteria
Study participants must:
1. Be adolescents (aged 12-18 years);
2. Have the ability to speak, read, and understand English. The parent(s) or legal
guardians of minors must also speak, read and understand English;
3. Be willing to provide consent/assent. Consent will be provided by parents/LAR/guardian
for youth under age 18 or by young adult participant, aged 18. Youth, aged 8-17, must
be willing to provide assent;
4. Have the ability to complete clinical evaluations and self-report measures;
5. Meet criteria for one of these three groups:
1. Adolescent with suicidal behaviors, defined as having a recent (within 3 months)
suicide attempt or suicidal ideation warranting urgent evaluation;
2. Adolescents at risk for mood disorders, defined by either personal history of
anxiety disorder or substance use disorder or a history of trauma, or a first
degree relative with a history of a mood disorder or suicidal history;
3. Healthy adolescents with no lifetime history of any psychiatric or substance use
disorders or a history of trauma. Additionally, no first-degree family member
with a history of a mood disorder or suicidal history..
Exclusion Criteria
Study participants must not:
1. Have current poorly controlled asthma, acute/chronic infection or other medical
condition(s) that may affect immune marker levels;
2. Have a current medication (e.g., corticosteroids) that may affect immune marker levels
of reactivity;
3. Have any condition for which, in the opinion of the investigator or designee, study
participation would not be in their best interest (including but not limited to
cognitive impairment, unstable general medical condition, intoxication, active
psychosis) or that could prevent, limit, or confound the protocol-specified
assessments;
4. Be unable to provide a stable home address and contact information
The RAD study is a longitudinal study to prospectively characterize the biological mechanisms
of resilience in adolescents and young adults at risk for developing depression. The study
will capture biomarkers from the domains of socio-demographic and clinical data, cognitive
and psychological assessments, fluid-based biomarkers, neuroimaging and EEG. Such biomarkers
will compose a human biosignature of resilience and identify risk factors for depression,
contributing to effective treatment selection or may represent moderators of response or
non-response to treatments in subjects with depression. A cohort of 1,500 participants, age
10-24 will be recruited over a 5 year period. Participants will be followed for 10 years
following an initial baseline visit. Study visits are conducted 4 times per year.
• Adolescents and young adults aged 10-24, male and female of all races and ethnicity.
• Participants must be English-speaking (because several study assessments are only
available in the English language), however the parent(s) or legal guardian may either
speak English or Spanish as the consenting process can be conducted bilingually.
• Adults age 18 and older must be able to provide written informed consent; for youth
younger than age 18, a parent or legal guardian must provide written informed consent,
and the child or teen must provide written informed assent.
• Ability to complete clinical evaluations and neuropsychological testing.
Exclusion Criteria:
• Individuals who are unable to provide informed consent.
• Participants who are non-English speaking.
• Individuals with any of the following psychotic features: MDD with psychotic features,
schizophrenia, schizoaffective disorder, or other Axis I psychotic disorder.
• Individuals with a depression diagnosis or a history of depression diagnosis at the
initial visit (participants who develop depression during the longitudinal follow-up
will continue in the study).
• A PHQ-9 score of 10 or greater.
• Individuals who are unable to provide a permanent home address and contact
information.
• Individuals with any condition for which, in the opinion of the investigator, study
participation would not be in their best interest (e.g., compromise their well-being)
or that could prevent, limit, or confound the protocol-specified assessments.