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Comparative Effectiveness Research Trial for Antidepressant Incomplete and Non-responders With TRD (ASCERTAINTRD)
This is a multi-site, randomized, open-label, effectiveness trial comparing three treatment arms for Major Depressive Disorder (MDD) patients with TRD who are currently on ongoing, stable and adequate antidepressant therapy (ADT). Adequate ADT is defined as a therapeutically sufficient dose for a sufficient treatment period, which would be expected to be effective as listed in the MGH Antidepressant Treatment Response Questionnaire (ATRQ). Patients will be randomized in a 1:1:1 fashion to one of three open-label treatment arms: a) aripiprazole augmentation, b) rTMS augmentation, and c) switching to venlafaxine XR or Duloxetine.
18 Years to 80 Years old
Inclusion Criteria:1. women and men ages 18-80, 2. with MDD, of at least 12 weeks duration, according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria confirmed by the Mini International Neuropsychiatric Interview (MINI; Sheehan et al, 1998), 3. have a Montgomery-Asberg Depression Rating Scale (MADRS
•Montgomery and Asberg, 1979) score of at least 20 at screen and baseline as assessed by site clinicians, 4. meet criteria for TRD during the current major depressive episode documented in the MGH Antidepressant Treatment History Questionnaire (ATRQ) (Chandler et al., 2010), which will be defined as being non-responders (less than 50% of symptom improvement) to two or more depression treatment trials of adequate dose and duration as defined by the MGH ATRQ, 5. are currently on an antidepressant of adequate dose (as defined by the MGH ATRQ) and duration (at least 8 weeks), with the antidepressant dose being stable over the past four weeks, and with documented (in the MGH ATRQ) non-response (less than 50% improvement) to the current antidepressant. 6. Patients who have passed the MGH CTNI remote assessment, with documentation provided to sites by MGH CTNI.
Exclusion Criteria:1. pregnant or breastfeeding women, women of childbearing potential who are not using an accepted means of birth control, or women with a positive urine pregnancy test, 2. patients who have received treatment with rTMS, aripiprazole, electroconvulsive therapy (ECT), or venlafaxine during the current episode, 3. patients who express an objection to receiving treatment with at least one of the three treatment arms of our study, 4. patients with any history of bipolar disorder or psychosis (diagnosed by MINI), 5. patients with active alcohol or substance abuse disorders within the past 6 months (diagnosed by MINI), 6. patients with suicidal ideation of the degree that, in the opinion of the evaluating clinician, participation in the study would place them at significantly increased risk of suicide, 7. patients with unstable medical issues of such degree that, in the opinion of the evaluating clinician, participation in the study would place them at significant risk of a serious adverse event, or patients with a screening hemoglobin A1c level greater than 7.5%, or patients with epilepsy, dementia, Parkinson's disease, or Huntington's Disease, 8. patients who have received treatment with vagus nerve stimulation (VNS), 9. patients who have not responded to more than five FDA-approved antidepressant treatment trials of adequate dose and duration during the current episode, or who did not respond to ECT in previous episodes 10. patients on excluded medications, 11. patients with a positive urine screen drug test for a substance for which they do not have a valid prescription for a valid medical reason, 12. patients with currently abnormal thyroid function tests, 13. patients who have received at least one dose of a monoamine oxidase inhibitor (MAOI) four weeks or less prior, and 14. for patients on concomitant psychotropic agents (anticonvulsants, benzodiazepines, hypnotics, opiates, triiodothyronine (T3), modafinil, psychostimulants, buspirone, melatonin, omega-3 fatty acids, folate, l-methylfolate, s-adenosyl methionine, lithium) not on the same dose for at least four weeks prior to study entry or who do not agree to continue at the same dose during the acute phase of the study. 15. Patients who do not meet safety criteria for TMS: history of seizures, cardiac pacemaker, DBS or VNS, brain aneurism clips or other metallic implants in the intracranial space. 16. Also excluded is an individual who has received any administration of ketamine in the current episode for the treatment of depression.
Drug: Aripiprazole, Device: Repetitive transcranial magnetic stimulation (rTMS), Drug: Venlafaxine XR
Treatment Resistant Major Depressive Disorder, Brain and Nervous System
A Probiotic Intervention to Prevent Relapse Following Hospitalization for Mania
This will be a 24-week, randomized, double-blind, placebo-controlled trial of adjunctive probiotic therapy in 66 persons hospitalized with a manic or mixed episode. The active study compound will consist of capsules containing approximately 10^9 colony forming units of the probiotic organisms, Lactobacillus GG and Bifidobacteria lactis strain Bb12. The dose has been selected because it has been used safely in other probiotic trials, was well-tolerated by the participants in two previous trials of individuals with schizophrenia or mania, and was utilized in the original trial on which this replication is based. This dose is higher than that available in most commercially-sold health food supplements. Following hospital discharge, participants will be randomized to receive adjunctive probiotic or placebo for a 24 week period. It is anticipated that of the 66 participants randomized, ~50 (75%) will complete the full 24 weeks of the study. The primary outcome is relapse, defined as re-hospitalization (e.g., admission to an inpatient unit) for psychiatric symptoms following a previous hospital discharge by at least 2 weeks. The occurrence of new mood episodes, the severity of psychiatric symptoms, and any changes in cognitive test scores over the course of the study will also be evaluated. Changes in the levels of inflammatory markers as well as changes in gut microbiota will be evaluated at three time intervals over the course of the study.
18 Years to 65 Years old
• Capacity for written informed consent
• Currently (or within the last 3 weeks) admitted to inpatient hospital for symptoms of mania.
• Primary Axis I diagnosis (DSM-5) at time of admission of bipolar I (single manic episode, most recent episode manic, or most recent episode mixed) OR schizoaffective disorder, bipolar type (manic or mixed state).
• Proficient in the English language.
• Available to attend follow-up visits.
• Substance- or medically-induced symptoms of mania at time of assessment.
• HIV infection or other immunodeficiency condition (such as receiving cancer chemotherapy).
• A serious medical condition that affects brain or cognitive functioning (e.g., epilepsy, serious head injury, concussion involving loss of consciousness, brain tumor, or other neurological disorder). Note that Hepatitis-C is not an exclusion criterion unless the participant has an acute infection.
• Diagnosis of Intellectual Disability or history of severe learning disorder.
• Diagnosis of alcohol or substance use disorder (moderate/severe) according to DSM-5 criteria within the last 3 months, or has a positive drug toxicity screen proximate to the time of recruitment.
• History of IV drug use.
• Participated in any investigational drug trial in the past 30 days.
• Pregnant, breastfeeding, or planning to become pregnant during the study period.
• Documented celiac disease (as such persons should be on a gluten-free diet as this is the standard care). Of note, we are not limiting the study to individuals with elevated levels of gliadin or casein antibodies as we intend to look at these levels as a predictor of response.
Combination Product: Probio-Tec BG-VCap-6.5, Other: Placebo
UT Southwestern; Parkland Health & Hospital System
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).
12 Years to 17 Years old
• 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.
• 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)
Suicidal Ideation, Suicide, Attempted
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.
50 Years and over
• 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
• 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
Comparing Virtual Reality (VR) to Non-VR for Decreasing Preoperative/Procedural Anxiety
The primary objective of the study is to utilize the modified Yale Preoperative Anxiety scale (mYPAS), a validated preoperative/procedural anxiety score, to measure preoperative anxiety via distraction in pediatric oncology patients undergoing port access. The hypothesis is that using Virtual Reality (VR) will objectively decrease anxiety scores measured by mYPAS by five percent (primary outcome). The secondary outcome will be the parents or the legally authorized representative (LAR) subjective reports of anxiety with the use of VR. The Kind VR device is used in house at Children's Health in the Dallas and Plano campuses. The VR device used in this study qualifies as exempt from FDA IDE regulations. It is a non-significant risk, non-invasive, interactive video device the user wears like goggles. The study carries minimal risks to the subjects and is designed to minimize patient discomfort from placement or motion sickness. Furthermore, the device has disposable covers for protection against infection and can be sanitized between uses, once the disposable covers are removed. Children's Health System of Texas (CHST) and this research group are not partnering entities with the Kind VR, and the Kind VR device is not being studied. The effect of virtual reality (VR) on preprocedural anxiety as measured by questionnaires and the observations of the modified Yale Preoperative Anxiety Scale (mYPAS) is being studied Most patients coming to the Clinic of Cancer and Blood Disorders (CCBD) are under chronic care for their ongoing disease and are likely to be coming to the CCBD at least twice in a 6-month period. The CCBD schedule will be reviewed by the researchers for patients age 5-12, requiring port access at least twice during the next six-month period. Patient families whose child meets the basic screening criteria, and have no exclusion criteria, will be approached privately as possible participants in the study. Up to 100 subjects will be enrolled over a 2-year period. Once the subject/parent or LAR agrees to participate, study staff will randomize the subjects into which standard of care distraction method for anxiety management they will receive first in this study.
5 Years to 12 Years old
• Any patient of the Children's Medical Center CCBD
• 5-12 years of age
• Patient requiring their port accessed twice or more within a 6 months period
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Subjects younger than 5 and older than 12
• Patients requiring recovery in PICU or sites other than PACU
• If parents or subject is not willing to participate
• Subjects with severe developmental delays and subjects with developmental challenges preventing them from keeping the VR device on are also excluded
• Patients who will not be in CCBD for port access at least twice in 6 months
Other: Virtual reality
Lymphoma, Sarcoma, Multiple Myeloma, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Leukemia, Other, Hodgkins Lymphoma, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Small Intestine, Soft Tissue, Preoperative Anxiety
virtual reality, preoperative anxiety, modified Yale Preoperative Anxiety Scale
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.
up to 2 Years old
• 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.
• 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
Drug: Sevoflurane, Drug: Remifentanil, Drug: Dexmedetomidine
Neurotoxicity, Anesthesia, Child Development
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.
18 Years to 65 Years old
• 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
• 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.
Drug: Aripiprazole, Drug: Placebo
Bipolar Disorder, Alcoholism, Alcohol Abuse
Alcohol Use Disorder, Bipolar Disorder, Mood, Alcohol Craving, Aripiprazole, Schizoaffective Disorder
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).
18 Years and over
• 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
• 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
Drug: Esketamine 56 mg, Drug: Esketamine 84 mg, Drug: Placebo
Depressive Disorder, Treatment-Resistant
Development of Pregnenolone as a Treatment for Depression R61
Pregnenolone, an over-the-counter supplement, is a naturally occurring neurosteroid made in the adrenal glands and brain. Preclinical research suggests pregnenolone has antidepressant, cognitive enhancing, and neuroprotective properties, particularly in women. The following hypothesis will be tested in this trial: pregnenolone is associated with improvement in depressive symptom severity in women that is associated with changes in the resting state functional connectivity (rsFC) and GABA.
18 Years to 65 Years old
• Women, ages 18-65 years, with current MDD (mild or moderate severity per DSM-5) based on SCID-CV.
• No psychotropic medications, other than PRN (as needed) hypnotics, within 28 days of randomization (medication free).
• PRN hypnotics allowed up to 3 days prior to study drug administrations but not while receiving study drug.
• Severe MDD based on DSM-5 severity criteria and/or a baseline HRSD score > 27 (consistent with severe depressive symptom severity).
• High risk for suicide (active SI with plan/intent or > 2 lifetime attempts in lifetime or any in the past 6 months).
• Treatment resistant depression (fail two adequate antidepressant trials or ECT during current episode).
• Vulnerable populations (e.g. pregnant/nursing, severe cognitive or intellectual impairment, incarcerated).
• Coronary artery disease, atrial fibrillation, stroke, deep vein thrombosis, pulmonary embolism or blood clotting disorder, or any severe, life threatening or unstable, medical condition.
• History of allergic reaction or side effects with prior pregnenolone use.
• Current substance use disorder defined as meeting criteria for a use disorder based on the SCID interview and self-reported use within the past 3 months, or a positive baseline urine drug screen.
• Current psychotic features (hallucinations, delusions, disorganized thought processes) or eating disorders.
• Anxiety disorders of sufficient severity to be the primary focus of clinical attention (e.g. severe obsessive compulsive or post-traumatic stress disorders).
• Hormone-sensitive conditions (i.e. breast cancer; uterine/ovarian cancer, endometriosis, uterine fibroids).
• Clinically significant laboratory, physical examination, or electrocardiogram (ECG) findings.
• Currently using oral contraceptives containing progestin (barrier methods allowed).
Drug: Pregnenolone 500 mg, Drug: Pregnenolone 800 mg, Drug: Placebo
Major Depressive Disorder
Depression, Pregnenolone, Women
Parkland Health & Hospital System
Noninvasive Brain Stimulation in Mild Cognitive Impairment and Dementia
The research objective of this study is to examine the efficacy of HD-tDCS to the preSMA/DACC region and its influence on verbal episodic memory in patients with MCI or dementia after 10 sessions of HD-tDCS. There will be three treatment arms: two active HD-tDCS (1 mA or 2 mA) and a sham group. A verbal episodic memory task will be completed at baseline, immediately following the last HD-tDCS session, and a 2-month follow-up.
50 Years and over
Inclusion Criteria:1. Age 50 and older 2. Fluent in English 3. Active diagnosis of MCI or dementia
Exclusion Criteria:1. Substance use disorder 2. Has metal fragments in head 3. 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: Active Transcranial direct current stimulation (STARStim 8), Device: Active Transcranial direct current stimulation (STARStim 8), Device: Sham Transcranial direct current stimulation (STARStim 8)
Dementia, Alzheimer Disease, Mild Cognitive Impairment, Brain and Nervous System
Transcranial direct current stimulation, Alzheimer Disease, Mild Cognitive Impairment, Dementia, MCI, Mild neurocognitive disorder, Amnestic, Pre- alzheimer
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.
14 Years to 18 Years old
Inclusion Criteria: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.
Drug: Docosahexaenoic acid (DHA)
Concussion, Mild Traumatic Brain Injury
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.
18 Years and over
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 ; 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
Depression, Unipolar Depression, Treatment Resistant Depression
Depression, Unipolar Depression, Treatment Resistant Depression, Magnetic Seizure Therapy, Suicidal Ideation, Electroconvulsive Therapy
UT Southwestern; Parkland Health & Hospital System
Internet-Based Cognitive Behavioral Therapy for Depressive Symptoms in Adolescents With Type 1 Diabetes Mellitus
This study evaluates the use of an established internet-based cognitive behavioral therapy intervention in a group of adolescents with type 1 diabetes and mild to moderate depressive symptoms. Half of the participants will receive the internet-based intervention while the other half will receive usual care.
13 Years to 17 Years old
• Age 13-17 receiving ongoing medical care in the Diabetes Clinic at Children's Medical Center Dallas.
• Patients must be fluent in English (the materials on the site have not been validated in any other language), be in at least the 8th grade, report/demonstrate comfort with use of a computer, and regular, convenient and discreet access to the internet.
• Patients must experience at least sub-threshold depression (CES-D score > 15).
• Patients must have had the diagnosis of type 1 diabetes for at least 12 months.
• Patients who are medically unstable during their diabetes clinic visit will be excluded (i.e. diabetes ketoacidosis, symptomatic hypoglycemia).
• Patients who are too severely depressed for this form of intervention (i.e. meet criteria for MDD, endorse suicidal intent, PHQ-A score ≥ 20), those with a diagnosis or symptoms of severe mental illness (schizophrenia, bipolar disorder), prior psychiatric hospitalization, prior self-harm attempt.
• Patients receiving ongoing counseling or therapy services within the last year, by a licensed professional (counselor, psychologist or psychiatrist).
• Patients who are currently taking or begin taking psychotropic medications during study participation will be excluded/withdrawn.
Type 1 Diabetes Mellitus, Depressive Symptoms
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.
45 Years and over
•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)
UT Southwestern; Parkland Health & Hospital System
Analgesics in the Pre-hospital Setting: Implications on Hemorrhage Tolerance - Morphine
We are examining how morphine (a commonly used pain medication) will alter responses to simulated blood loss in humans. To simulate blood loss in our research laboratory, participants will complete a test with their lower body in a custom-designed vacuum chamber for a brief period of time.
18 Years to 45 Years old
Phase 1/Phase 2
• Non-obese (body mass index less than 30 kg/m2)
• Body mass greater than or equal to 65 kg
• Subjects who have cardiac, respiratory, neurological and/or metabolic illnesses
• Any known history of renal or hepatic insufficiency/disease
• Pregnancy or breast feeding
• Current smokers, as well as individuals who regularly smoked within the past 3 years
• Positive urine drug screen
• Currently taking pain modifying medication(s)
Drug: Morphine, Other: Placebo
rTMS for Stimulant Use Disorders (CTN-0108)
The purpose of the study is to determine feasibility of repetitive transcranial magnetic stimulation (rTMS) for individuals with moderate to severe cocaine or methamphetamine use disorder (CUD/MUD). Potential participants will be age 18-65, and interested in cutting down or stopping use. Participants will be randomized to one of two groups; groups will receive rTMS or sham rTMS (placebo) over the course of an 8-week treatment period, and complete follow-up assessments at the end of treatment, 12, and 16 weeks post-randomization.
18 Years to 65 Years old
• 18-65, inclusive
• Have a diagnosis of moderate or severe Cocaine or Methamphetamine Use Disorder (CUD/MUD) over the past 12 months (as determined by DSM-5 diagnostic criteria).
• Have used cocaine or methamphetamine on at least 10 of the last 30 days (based on Timeline Follow-Back).
• Be interested in decreasing cocaine and/or methamphetamine use.
• If female, willing to use appropriate birth control method during the treatment phase of the study.
• Be able to understand the study procedures and provide written informed consent to participate in the study.
• If prescribed benzodiazepines or anticonvulsants, must be on a stable dose for at least 4 weeks prior to consent.
• A Diagnostic and Statistical Manual (DSM-5) diagnosis of moderate or severe SUD of any substance other than cocaine or methamphetamine based on DSM-5.
• History of a serious medical disorder that, in the opinion of the Medical Clinician, would make it unsafe to participate in the study or may prevent collection of study data.
• Is currently engaged in formal SUD treatment.
• Documented history of unprovoked seizure (lifetime) or any seizure in the past 6 months.
• Documented history of brain lesion(s) and/or tumor(s).
• Metal implants or non-removable metal objects above the waist.
• Currently pregnant.
• Lifetime history of prior clinical treatment with TMS.
• Current or lifetime bipolar disorder.
• Current psychotic disorder or psychotic depression.
• Serious risk of homicide or suicide.
• Are a prisoner or in police custody at the time of eligibility screening.
• Previously randomized as a participant in the study.
• Planned admission to a residential treatment facility or other formal SUD treatment program.
• Unwilling or unable to follow study procedures.
Device: rTMS, Device: Sham (Placebo)
Cocaine Dependence, Cocaine Abuse, Methamphetamine Dependence, Methamphetamine Use Disorder, Brain and Nervous System, Psychiatric Disorders, Cocaine Use Disorder, Methamphetamine Abuse, Stimulant Use, Stimulant Abuse, Stimulant Use Disorder
Stimulant, Cocaine, Methamphetamine, Repetitive Transcranial Magnetic Stimulation, rTMS
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.
18 Years and over
• 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
• 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)
Drug: Olanzapine, Drug: Megestrol Acetate, Other: Questionnaire Administration
Lymphoma, Sarcoma, Anorexia, Multiple Myeloma, Mycosis Fungoides, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Leukemia, Other, Hodgkins Lymphoma, Heart, Kaposis sarcoma, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Psychiatric Disorders, Small Intestine, Soft Tissue, Unknown Sites, Ill - Defined Sites
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.
13 Years to 18 Years old
• 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.
18 Years to 65 Years old
Inclusion Criteria: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.
Drug: Ketamine Hydrochloride, Drug: Midazolam injection
Major Depressive Disorder, Psychiatric Disorders, Healthy Controls
major depressive disorder, MDD, depression, depressive disorder, depression symptoms, healthy controls, irritability, ketamine
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.
18 Years and over
• 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
• 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
Drug: Semaglutide, Drug: Placebo (semaglutide)
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.
18 Years to 70 Years old
• 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
• 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
Drug: Placebo, Drug: Citicoline, Drug: Pregnenolone
Bipolar Disorder, Alcohol Use Disorder
Alcohol Use Disorder, Bipolar Disorder, Mood, Alcohol craving, Pregnenolone, Citicoline
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.
40 Years to 67 Years old
Phase 1/Phase 2
Inclusion Criteria: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.
• 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.
18 Years to 40 Years old
• 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)
• 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)
Drug: Hydrocortisone Oral, Drug: Placebo Oral Tablet
Depression, Healthy Volunteers, Hydrocortisone, Psychiatric Disorders
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.
18 Years and over
Inclusion Criteria: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
Drug: Bupropion, Behavioral: Behavioral activation therapy, Drug: Placebo, Other: Clinical Management
Major Depressive Disorder, Chronic Kidney Diseases, Kidney
UT Southwestern; Parkland Health & Hospital System
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 Years to 55 Years old
• 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)
• 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
Schizophrenia, Bipolar, Psychosis, Biomarker, Biotype, BSNIP, B-SNIP, IEA
PST for Care Partners of Adults With Alzheimer's and Alzheimer'S-related Dementia
Caregivers of individuals with Alzheimer's disease and related dementia rarely get the preparation or training they need to manage their caregiving responsibilities and to successfully balance their own self-care and their caregiving roles. As a result, caregivers often experience caregiver burden, emotional distress, and substance abuse. Therefore, there is a critical need to support the emotional and social functioning of caregivers to improve their health and well-being and to prevent caregiver burden and poor coping. Problem solving training (PST) is an evidence-based approach that teaches and empowers individuals to solve emergent problems contributing to their depressive symptoms, helps improve coping skills and increases self-efficacy. However, critical gaps in knowledge and care remain regarding the necessary components of training (eg. How many sessions? What is the influence of personal factors?) that affect how effective PST is for individual caregivers. Finally, caregiver interventions have almost exclusively been tested in English-speaking caregivers, further contributing to existing health disparities among minority groups. To address this critical need, Dr. Shannon Juengst, Assistant Professor of Physical Medicine and Rehabilitation was awarded a new Texas Alzheimer's Research and Care Consortium Collaborative Research Grant entitled, "Problem Solving Training (PST) for English- and Spanish-speaking Care Partners of Adults with Alzheimer's and Alzheimer's Related Dementia." For this project, Dr. Juengst has assembled a strong, multidisciplinary team with Dr. Gladys Maestre, Professor of Biomedical Sciences and Director of the NIA funded-Alzheimer's Disease Resource Center for Minority and Aging Research and Memory Disorders Center at UT Rio Grande Valley and Dr. Matthew Smith, Associate Professor of Environmental and Occupational Health and Co-Director of the Center for Population Health and Aging at Texas A&M University. This project will establish the necessary guidelines for an evidence-based, implementable problem-solving intervention for both English- and Spanish-speaking caregivers to improve their health and well-being and identify potential mechanisms of action for such training.
18 Years and over
• PHQ2 Score of 2 or higher and/or ZBI4 Score of 2 or higher
• 18 years or older
• Able to speak fluently in English or Spanish
• Cognitively able to make decisions, as determined by ability to provide informed consent
• Care partner/caregiver to individual with AD/ADRD
• Individual must have at least one year or more of a relationship with patient with AD/ADRD
• Dispute over care partner's role in the care of patient
• Has previously participated in other PST study at UTSW within the past year
• Does not meet all the inclusion criteria
Behavioral: Problem Solving Training
Alzheimer Disease, Mild Cognitive Impairment (MCI), Frontotemporal Degeneration (FTD), Lewy Body Dementia (LBD), Vascular Contributions to Cognitive Impairment and Dementia (VCID), Mixed Etiology Dementias (MED)
Alzheimer Disease, Frontotemporal Degeneration, Lewy Body Dementia, Vascular contributions to cognitive impairment and dementia, Mixed etiology dementias, Mild Cognitive Impairment, Care partner, Caregiver, Alzheimer's-related Dementia
UT Southwestern; Parkland Health & Hospital System
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.
10 Years and over
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
Suicide Treatment Alternatives for Teens (START)
Randomized trial to compare inpatient care versus outpatient crisis intervention clinic. This study plans to enroll up to 1,000 participants across 4 sites in a 5 years period.
12 Years to 18 Years old
• Adolescents (12 to 18 years old) who were brought to the ED due to suicidal thoughts or behaviors and require a higher level of care (OCIC or inpatient)
• The presence of a legal guardian
• Adolescents with suicidal thoughts that place themselves at a serious imminent risk of suicide based on clinical judgment and/or responses on the Concise Health Risk Tracking Self-Report (CHRT-SR) (a score of 23 or higher on the 14 item CHRT-SR) 70-72
• Adolescents who require 24 hour/day supervision but no adult can provide 24 hour/day supervision outside of the hospital
• Adolescents with suicidal thoughts who had prior OCIC treatment in the past 12 months will be excluded
• Adolescents without the ability to answer survey questions will be excluded
Behavioral: Inpatient Psychiatry, Behavioral: Outpatient Crisis Intervention Clinic
Suicidal Ideation, Psychiatric Disorders
Suicide, Suicidal, Adolescent
Quantra QStat in Trauma and Liver Transplant
This is a multi-center prospective, observational study of the Quantra System with the QStat Cartridge in trauma patients and patients undergoing liver transplant.
18 Years and over
• Subject is > 18 years
• Subject is a trauma patient experiencing traumatic injuries requiring a full trauma team response OR Subject is a patient undergoing liver transplant surgery.
• Subject, or subject's legally authorized representative (LAR), is willing to provide informed consent, either prospectively or by deferred consent, OR Institutional Review Board (IRB)/Ethics Committee (EC) has waived the requirement to obtain informed consent.
• Subject is younger than 18 years of age
• Subject is pregnant.
• Subject is incarcerated at the time of the study.
• Subject is currently enrolled in a distinct study that might confound the result of the proposed study
• Subject is affected by a condition that, in the opinion of the surgical team, may pose additional risks.
Diagnostic Test: Quantra System
Hemorrhage, Trauma, Liver Transplant
Viscoelastic testing, Coagulation, Trauma, Liver Transplant, Quantra, QStat
UT Southwestern; 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.
22 Years and over
• 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
Other: No Intervention
Intellectual Disability, Phelan-McDermid Syndrome, Autism Spectrum Disorder
Phelan-McDermid Syndrome, PMS, Genotype, Phenotype, Mapping, 22q13 Deletion Syndrome, SHANK3, Autism Spectrum Disorder, ASD, Intellectual Disability, ID