Search Results Within Category "Mental Health"
Treatment ResistAnt Depression Subcallosal CingulatE Network DBS (TRANSCEND) (TRANSCEND)
The goal of this clinical trial is to evaluate the effectiveness and safety of bilateral stimulation of the subcallosal cingulate white matter (SCCwm) using Deep Brain Stimulation (DBS) as an adjunctive treatment of non-psychotic unipolar Major Depressive Disorder (MDD) in adults.
Hila Abush Segev hila.abushsegev@utsouthwestern.edu
Identifying Strategies to Curtail Weight Regain After GLP-1 Receptor Agonist Treatment Cessation
Longitudinal studies show there is a steep increase in weight regain in the first 3-4 months after stopping GLP-1 receptor agonist medications (GLP-1s) and most patients regain most of their weight within a year. Insurers now question the utility of GLP-1s for weight loss as they are hesitant to cover these costs long-term (~$833 per person per month). Some patients would also prefer not to take these medications in perpetuity and are likely to struggle with lifelong adherence. These challenges present an opportunity to test alternative interventions, such as meal replacements and behavioral treatments, to support weight maintenance after successful weight loss with GLP-1s. This regimen would allow patients to benefit from significant weight loss in the first year of taking GLP-1s and use more cost effective and sustainable strategies for long-term maintenance.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Carolyn.Haskins@UTSouthwestern.edu
• 18 years of age or older;
• ability to read, write, and speak English;
• ability to provide informed consent;
• greater than 10% GLP-1 Receptor Agonist induced weight loss
• less than 30-days since GLP-1 Receptor Agonist cessation;
• willing to participate. Exclusion criteria:
• major psychiatric illness or substance misuse that could impair ability to participate;
• presence of a medical condition or dietary restriction precluding eating study meals or weight loss (e.g., medical condition requiring liquid diet, pregnancy, eating disorder);
• participation in a study or program involving medically tailored meals or Noom® within the past 12-months.
Trial of Naltrexone/Bupropion for the Treatment of Methamphetamine Use Disorder
The primary objective of this study is to evaluate the efficacy of extended release naltrexone plus bupropion XL (XR-NTX/BUP-XL) compared to matched injectable and oral placebo (iPLB/oPLB) in reducing methamphetamine (MA) use in individuals with moderate or severe methamphetamine use disorder (MUD) seeking to stop or reduce MA use.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Teresa.Slettebo@UTSouthwestern.edu
• Is 18 to 65 years of age;
• Meets DSM-5 criteria for moderate or severe MUD (4 or more criteria);
• Is interested in reducing or stopping MA use;
• Is able to speak English sufficiently to understand the study procedures and provide written informed consent to participate in the study;
• Self-reports MA use on 18 or more days in the 30-day period prior to consent using the Timeline Followback (TLFB);
• Provides at least 2 urine samples positive for MA out of up to 3 tests, which will occur at least 2 days apart within a 10-day period;
• If assigned as female at birth and/or currently has a uterus, is not pregnant, agrees to use acceptable birth control methods, and have periodic urine pregnancy testing done during participation in the study unless documentation of hysterectomy provided;
• Is not physically dependent on opioids and meets subjective and objective measures of being opioid-free prior to naltrexone injection per study medical clinician's determination, including, if clinically required, a negative naloxone challenge;
• Is willing to comply with all study procedures and medication instructions;
• Agrees to use a smartphone app (downloaded for free to own device or on a study provided smartphone device) to take daily videos of medication dosing.
• Has an acute medical or psychiatric disorder that would, in the judgment of the study medical clinician, make participation difficult or unsafe;
• Has suicidal or homicidal ideation that requires immediate attention;
• Has a history of epilepsy, seizure disorder, or head trauma with neurological sequelae (e.g., loss of consciousness that required hospitalization); current anorexia nervosa or bulimia; or any other conditions that increase seizure risk in the opinion of the study medical clinician;
• Has evidence of second or third degree heart block, atrial fibrillation, atrial flutter, prolongation of the QTc, or any other finding on the screening ECG that, in the opinion of the study medical clinician, would preclude safe participation in the study;
• Has Stage 2 hypertension as determined by the study medical clinician (e.g., greater than or equal to 160/100 in 2 out of 3 readings during screening);
• Has any elevated bilirubin test value per laboratory criteria OR any other liver function test (LFT) value \> 5 times the upper limit of normal per laboratory criteria;
• Has a platelet count \<100 x 10exp3/microliter;
• Has a body habitus that precludes gluteal intramuscular injection of XR-NTX in accordance with the administration equipment (needle) and procedures;
• Has a known allergy or sensitivity to bupropion, naloxone, naltrexone, PLG (polyactideco-glycolide), carboxymethylcellulose or any other component of the XR-NTX diluents;
• Has been in a prior study of pharmacological or behavioral treatment for MUD within 6 months of study consent;
• Has taken an investigational drug in another study within 30 days of study consent;
• Has been prescribed and taken naltrexone or bupropion within 30 days of study consent;
• Is concurrently enrolled in formal behavioral or pharmacological Substance Use Disorder (SUD) treatment services;
• Is receiving ongoing treatment with tricyclic antidepressants, xanthines (i.e., theophylline and aminophylline), systemic corticosteroids, nelfinavir, efavirenz, chlorpromazine, MAOIs, central nervous system stimulants (e.g., Adderall, Ritalin, etc.), or any medication that, in the judgment of the study medical clinician, could interact adversely with study medications;
• Has a current pattern of alcohol, benzodiazepine, or other sedative hypnotic use which would preclude safe participation in the study as determined by the study medical clinician;
• Requires treatment with opioid-containing medications (e.g., opioid analgesics) during the study period;
• Has a surgery planned or scheduled during the study period;
• Is currently in jail, prison or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) that could prevent participation in the study or in any study activities;
• If assigned as female at birth and/or currently has a uterus, is currently pregnant, breastfeeding, or planning on conception.
Studying the Health of Asians to Advance Knowledge, Treatments, and Interventions for Depression (SHAKTI)
SHAKTI (from the Sanskrit word for "power") is a 5-year natural history, longitudinal, prospective study of a cohort of 6,000 participants that will help uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to antidepressant treatment response (remission, recurrence, relapse and individual outcomes in depressive disorders) and resilience. As this is an exploratory study, we will assess a comprehensive panel of carefully selected participant specific parameters - socio-demographic (age, sex, gender, race, ethnicity, economic); life habits (physical activity, substance use); clinical (medical history, anxious depression, early life trauma), biological (biomarkers in blood, saliva, urine, stool), behavioral (cognitive, emotional), neurophysiological (EEG), and neuroimaging (magnetic resonance imaging; MRI) with the goal of developing the most robust predictive models of depression treatment response and of outcomes.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Afrida.Khurshid@UTSouthwestern.edu
• Adult or youth aged 10 years or older
• Self-identify fully or partially as being of Asian or Pacific Islander descent such as: East Asian, South Asian, Southeast Asian, Southwest Asian, Central Asian, Oceanian, Pacific Islander, Polynesian, Micronesian, Melanesian
• Have the ability to speak, read, and understand English. The parent(s) or legal guardians of minors must also speak, read and understand English.
• Have the ability to complete clinical evaluations, neuropsychological testing, and self-report measures.
• Meet criteria for one of these three groups:
• Have a lifetime or a current diagnosis of a mood disorder (such as depression, bipolar disorder, anxiety) based upon a semi- structured diagnostic interview (must be a non-psychotic depressive disorder)
• Be at risk for developing mood disorders
• Healthy Control Group
• History of schizophrenia, schizoaffective disorders or chronic psychotic disorders based upon a semi-structured diagnostic interview.
• Unable to provide a stable home address and contact information.
• 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.
• Requires immediate hospitalization for psychiatric disorder or suicidal risk as assessed by a licensed study clinician.
Emotional Cognition: Establishing Constructs and Neural-Behavioral Mechanisms in Older Adults With Depression (ENSURE)
This is a cross-sectional pilot study designed to establish hot and cold cognitive functions and underlying neurocircuitry in older adults with MDD. The investigators will study 60 participants aged 21-80 years old with MDD. All participants will undergo clinical and neurocognitive assessment, and Magnetoencephalography (MEG)/Magnetic resonance imaging (MRI) procedures at one time point. The investigators will also enroll 60 demographically matched comparable, never-depressed healthy participants (controls) to establish cognitive benchmarks. Healthy controls will complete clinical and neurocognitive measures at one time point. To attain a balanced sample of adults across the lifespan, the investigators will enroll participants such that each age epoch (e.g., 21-30, 31-40, etc.) has a total of ten subjects (n=10) in both the healthy control cohort and depressed cohort.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aatika.Parwaiz@UTSouthwestern.edu
• Male and female participants
• Age between 21-80 years old
• DSM-5 diagnosis of major depressive disorder (MDD) based on Mini Neuropsychiatric Interview
• Inventory of Depressive Symptomatology-Clinician Rated version (IDS-C) total score > 14
• Able to read, write, and comprehend English
• Provide informed consent; willing to comply with study protocol
• History of bipolar disorder, schizophrenia, or schizoaffective disorder
• Presence of psychotic features
• Lifetime central nervous system (CNS) disease (including head injury with loss of consciousness > 5 minutes)
• History of neurodevelopmental disorder (e.g., Autism spectrum disorder)
• History of medical conditions that can affect neurocognitive function as well as be confounded with age (e.g., thyroid disease, endocrine illnesses)
• History and current use of hormonal replacement therapy
• Women who are pregnant
• Current use of medications with known impacts on neurocognitive function (e.g., acetylcholinesterase inhibitors, amphetamine, methylphenidate, vortioxetine, sedatives)
• Alcohol/substance use disorder within past 3 months
• DSM-5 diagnosis of major cognitive impairment
• Current sensory or physical impairment that interferes with testing.
• Contraindication to MRI and MEG (only for depressed participants) (e.g., any electronic / metallic implants near or within the head or body, claustrophobia)
Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRD
Efficacy, Safety, and Tolerability of two administrations of COMP360 in participants with treatment-resistant depression (TRD)
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ann.House@UTSouthwestern.edu
• Aged ≥18 years at Screening
• Major depression without psychotic features (single or recurrent episode as informed by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition [DSM-5])
• If the current major depressive episode is the participant's first lifetime episode of depression, the length of the current episode must be ≥3 months and ≤2 years at Screening
• MADRS total score ≥20 at Screening and Baseline to ensure at least moderate severity of depression
• TRD, defined as failure to respond to an adequate dose and duration of two, three, or four different pharmacological treatments for the current episode as determined through the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and using the supplementary advice on additional antidepressants not included in MGH-ATRQ
• At Screening, agreement to discontinue all prohibited medications Key
• Prior or ongoing bipolar disorder, any psychotic disorder, including schizophrenia, schizophreniform disorder, schizoaffective disorder, brief psychotic disorder (unless substance induced or due to a medical condition), antisocial personality disorder as assessed by a structured clinical interview (MINI 7.0.2)
• Lifetime paranoid, schizoid, schizotypal, histrionic, narcissistic personality disorder, or any ongoing serious psychiatric comorbidity based on medical history and clinical judgement
• Borderline personality disorder as demonstrated by medical history or the Mini International Neuropsychiatric Interview Plus (MINI plus) - borderline personality disorder module
• Ongoing post-traumatic stress disorder, obsessive-compulsive disorder, or anorexia nervosa as assessed by medical history and a structured clinical interview (MINI
• 0.2)
• Psychiatric inpatient within the past 12 months prior to Screening
• Use of electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation during the current depressive episode
• Transcranial magnetic stimulation within the past six months prior to Screening
• Current enrolment in a psychological therapy programme that will not remain stable for the duration of the study. Psychological therapies cannot have been initiated within 30 days prior to Screening
• Exposure to COMP360 psilocybin therapy prior to Screening
Cognitive Outcomes of Brain Stimulation As a Later-in-Life Treatment (COBALT)
This is a pilot study being done to attempt to improve episodic memory problems in persons with mild cognitive impairment (MCI) or dementia. The pre-supplemental motor area (preSMA) and dorsal anterior cingulate cortex (dACC) have been shown to play a role in episodic memory and language retrieval. Prior studies have suggested that neurostimulation targeting this region can improve episodic memory and word recall. The purpose of this study is to examine the efficacy of high-definition transcranial direct current stimulation (HD-tDCS) to the preSMA/dACC region and its influence on word retrieval and other cognitive functions in patients with MCI or dementia. Entraining the preSMA/dACC circuit with 10 sessions of HD-tDCS will allow us to study whether neurostimulation may be an effective treatment.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hannah.Cabrera@UTSouthwestern.edu
A Study of Aticaprant 10 Milligrams (mg) as Adjunctive Therapy in Adult Participants With MDD With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy (VENTURA-2)
The purpose of this study is to evaluate the efficacy of aticaprant compared with placebo as adjunctive therapy to an antidepressant in improving depressive symptoms in adult participants with major depressive disorder (MDD) with moderate to severe anhedonia (ANH+) who have had an inadequate response to current antidepressant therapy with a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Elizabeth.Dedrick@UTSouthwestern.edu
A Study of Aticaprant in Adult and Elderly Participants With Major Depressive Disorder (MDD) (VENTURA-LT)
The purpose of this study is to assess the long-term safety and tolerability of aticaprant administered as adjunctive therapy to a current antidepressant (selective serotonin reuptake inhibitor \[SSRI\] or serotonin and norepinephrine reuptake inhibitor \[SNRI\]) in all participants with major depressive disorder (MDD).
studyfinder@utsouthwestern.edu
Pathways Relating Amnestic MCI to a Mild Traumatic Brain Injury History (PATH)
This study will probe if the biological changes in amnestic mild cognitive impairment (aMCI) are related to a history of mild traumatic brain injury (mTBI) using high definition transcranial direct current stimulation (HD-tDCS) and blood-derived biomarker tools. Participants who Do as well as those who Do Not have a history of mTBI will be enrolled in the study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hannah.Cabrera@UTSouthwestern.edu
• Active diagnosis of amnestic mild cognitive impairment
• Presence of an mTBI history for the mTBI+ group; absence of an mTBI history for a control sample
• Female and male subjects
• All races/ethnicities
• Age 55 years and older
• Fluent in English
• Mild traumatic brain injury within past year
• Lifetime history of moderate or severe brain injury
• Lifetime major neurologic syndromes (e.g., stroke, epilepsy, brain tumor)
• Lifetime major cardiovascular conditions (e.g., heart attack, heart failure)
• Current substance use disorder
• Current major psychiatric disorders (e.g., major depressive disorder, bipolar disorder)
• Current vision or hearing impairment that interferes with testing
• Any electronic and or metallic implants in the skull or brain
• Current medication use known to alter HD-tDCS reactivity
Impact of Intensive Treatment of SBP on Brain Perfusion, Amyloid, and Tau (IPAT Study) (IPAT)
The purpose of this study is to determine if intensive lowering of systolic blood pressure (SBP), using FDA approved medications (antihypertensive), reduces Alzheimer's Disease pathology (i.e., excessive brain amyloid and tau protein deposition) in older adults at high risk for memory decline or dementia.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Margaret.Mcgregor@UTSouthwestern.edu
• Plans to move outside the clinic catchment area in the next 2 years;
• Significant concerns about participation in the study from spouse, significant other, or family members;
• Lack of support from primary health care provider;
• Residence too far from the study clinic site such that transportation is a barrier including persons who require transportation assistance provided by the study clinic funds for screening or randomization visits;
• Residence in a nursing home; persons residing in an assisted living or retirement community are eligible if they meet the other criteria;
• Other medical, psychiatric, or behavioral factors that, in the judgment of the site PI or clinician, may interfere with study participation or the ability to follow the study Protocol.
• Couples or significant partners who live together cannot be enrolled or participate simultaneously in the study.
Caloric Restriction and Activity to Reduce Chemoresistance in B-ALL (IDEAL2)
This study is for older children, adolescents, and young adults with B-cell Acute Lymphoblastic Leukemia (B-ALL). Higher amounts of body fat is associated with resistance to chemotherapy in patients with B-ALL. Chemotherapy during the first month causes large gains in body fat in most people, even those who start chemotherapy at a healthy weight. This study is being done to find out if caloric restriction achieved by a personalized nutritional menu and exercise plan during routine chemotherapy can make the patient's ALL more sensitive to chemotherapy and also reduce the amount of body fat gained during treatment. The goals of this study are to help make chemotherapy more effective in treating the patient's leukemia as demonstrated by fewer patients with leukemia minimal residual disease (MRD) while also trying to reduce the amount of body fat that chemotherapy causes the patient to gain in the first month.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
• Patients must be ≥ 10.0 and <26.0 years of age.
• Patients must have a diagnosis of de novo B-ALL
• Patients must have a M3 marrow (>25% blasts by morphology) or at least 1,000/µL circulating leukemia cells in PB confirmed by Flow Cytometry (or other convincing evidence of a B-ALL diagnosis not meeting above criteria following central review by the Study Hematopathologist and Study Chair or Vice-Chair).
• The treatment regimen must be the first treatment attempt for B-ALL-
• Must be a multi-agent induction regimen inclusive of vincristine, glucocorticoid, pegaspargase/calaspargase, and daunorubicin or doxorubicin and with a planned duration <35 days.
• Organ function must meet that required for initiation of chemotherapy
• Patients at diagnosis must meet Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age (or be expected to recover prior to Day 8) .
• If the patient is a female of childbearing potential, a negative urine or serum pregnancy test is required within two weeks prior to enrollment.
• Patient will be excluded if they are underweight at time of enrollment (BMI% <5th percentile for age for patients age 10-19 years, BMI <18.5 in patients 20-29 years).
• Patients with Down syndrome or a DNA fragility syndrome (such as Fanconi anemia, Bloom syndrome) will be excluded.
• Patient receiving a SJCRH-style "Total Therapy" regimen will be excluded.
• Patients receiving anti-CD20 monoclonal antibody therapy during induction therapy.
• Patients will be excluded if they received treatment for a previous malignancy.
• Patient will be excluded if they are pregnant.
• Patient will be excluded if they have a pre-diagnosis requirement for enteral or parenteral supplementation .
• Patient will be excluded due to inability to perform the intervention (e.g., specific nutritional needs, severe developmental delay, paraplegia)
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results
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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Elizabeth.Dedrick@UTSouthwestern.edu
• Male or female subjects, 18-65 years of age and body weight less than or equal to 120 kg on baseline visit.
• 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.
• 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.
• 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.
• 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].
• Subjects with MDD should be willing to participate in neuroimaging scans before and after infusions, and be willing to undergo infusions with study drug.
• Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, pervasive developmental disorder or intellectual development disorder.
• 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.
• 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.
• 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.
• Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, immunologic, or hematologic disease.
• 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).
• Presence of a significant neurological disease such as Parkinson's disease, primary or secondary seizure disorders, intracranial tumors, or severe head trauma.
• Presence of neurocognitive or dementing disorders.
• Clinically significant abnormalities of laboratories, physical examination (including unstable hypertension - systolic blood pressure >170, diastolic blood pressure >100), or electrocardiogram at screening visit.
• Subjects judged to be at serious and imminent suicidal or homicidal risk by the PI or another study-affiliated psychiatrist.
• Any contraindications to MRI, including pacemakers or metallic objects in the body.
• Any claustrophobia or other conditions which may result in inability to lie still in the MRI scanner for 1 hour or more.
• Allergy to ketamine or midazolam in subjects with MDD.
• Must not be on any prohibited concomitant medication.
Behavioral Activation Teletherapy to Increase Physical Activity (BAT)
This is a pilot study of acceptability, feasibility, and preliminary efficacy of a brief, 10-session Behavioral Activation intervention delivered via teletherapy to increase physical activity and treat depressive symptoms.
Lynnel Goodman, PhD lynnel.goodman@utsouthwestern.edu
Fannie M Brito fanny.brito@utsouthwestern.edu
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.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Aging and Disease Course: Contributions to Lifespan Neurobiology of Schizophrenia
The 2020 NIMH Strategic Plan for Research calls for investigations targeting neurobiology of mental illness across the lifespan. Growing evidence suggests that lifespan neurobiology of schizophrenia (SZ) incorporates two distinct dimensions: aging and disease course. However, their clinical correlates, associated biomarker trajectories, and implications for treatment are unknown. This study will investigate differential aspects of SZ neurobiology captured by aging and disease course, in order to develop specific biomarkers which may offer actionable targets for SZ stage-dependent intervention. The study is predicated on a novel mechanistic Model of SZ Trajectories across the Adult Lifespan, positing distinct biological fingerprints within the anterior limbic system for aging and disease course in SZ: (1) alterations in the circuit's function and structure that occur earlier in the lifespan and are larger in magnitude than the alterations expected with normal aging (accelerated aging dimension); and (2) regionally-specific anterior limbic "hyperactivity" in early SZ, with a subsequent transformation into "hypoactivity" in advanced SZ (disease course dimension). In a sample of SZ and matched healthy controls (n=168, 84/group) aged 18-75 years the investigators will ascertain a broad panel of biomarkers \[via multimodal brain imaging: optimized 1H-MRS, high-resolution task-based fMRI, perfusion (Vascular Space Occupancy) and structural MRI\], along with comprehensive cognitive and clinical assessments. All measures will be acquired at baseline and repeated at 2-year longitudinal follow-up. Using cutting-edge computational approaches, the study will examine (i) effects of aging and SZ course on anterior limbic system biomarkers; (ii) lifespan trajectories for different biomarkers; (iii) patterns of limbic system biomarkers in age- and SZ course-based subgroups (e.g., Younger vs. Older, Early-Course vs. Advanced SZ), as well as in data-driven subgroups (e.g., those with vs. without accelerated aging profiles); and (iv) associations between biomarkers and cognitive and clinical outcomes. This research will advance the field by providing novel biomarkers that capture unique neurobiological contributions of aging and disease course in SZ, and will motivate future studies on SZ mechanisms across the lifespan and development of precision treatments.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Monserrat.Feria-Vargas@UTSouthwestern.edu
Characterizing Inflammatory Profiles and Suicidal Behavior in Adolescents
Despite increasing suicide rates in adolescents, there remains a paucity of approaches to use to prevent re-attempts. Any hope for breaking the code to prevent youth suicide lies in understanding biological factors that play a role. Evidence suggests that inflammation and immune system dysfunction may be linked to suicide. The investigators will develop immune profiles for adolescents with suicidal behavior and those at risk in order to develop tools that can be implemented for prevention efforts. This study involves blood draws, answering questions, and completing questionnaires - no treatment or intervention is provided as part of this study. Participants will be screened to see if they qualify for this study using questionnaires. Participants will be teens (ages 12-18 years) with recent suicidal behavior, teens at-risk for developing depression, and healthy control teens. Participants complete all study-related tasks four times over a period of 12 months. Electronic surveys will be sent to participants to complete monthly. Both the adolescent and if applicable, their parent (or legally authorized representatives, LARs), will answer questions regarding depression, anxiety, and suicidal thoughts/behaviors.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Abby.Starling@UTSouthwestern.edu
• Be adolescents (aged 12-18 years);
• Have the ability to speak, read, and understand English. The parent(s) or legal guardians of minors must also speak, read and understand English;
• Be willing to provide consent/assent. Consent will be provided by parents/LAR/guardian for youth under age 18 or by young adult participant, aged 18. Youth, aged 8-17, must be willing to provide assent;
• Have the ability to complete clinical evaluations and self-report measures;
• Meet criteria for one of these three groups:
• Adolescent with suicidal behaviors, defined as having a recent (within 3 months) suicide attempt or suicidal ideation warranting urgent evaluation;
• Adolescents at risk for mood disorders, defined by either personal history of anxiety disorder or substance use disorder or a history of trauma, or a first degree relative with a history of a mood disorder or suicidal history;
• Healthy adolescents with no lifetime history of any psychiatric or substance use disorders or a history of trauma. Additionally, no first-degree family member with a history of a mood disorder or suicidal history.. Exclusion Criteria Study participants must not:
• Have current poorly controlled asthma, acute/chronic infection or other medical condition(s) that may affect immune marker levels;
• Have a current medication (e.g., corticosteroids) that may affect immune marker levels of reactivity;
• Have any condition for which, in the opinion of the investigator or designee, study participation would not be in their best interest (including but not limited to cognitive impairment, unstable general medical condition, intoxication, active psychosis) or that could prevent, limit, or confound the protocol-specified assessments;
• Be unable to provide a stable home address and contact information
Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents
This project aims to examine the efficacy of ketamine, a rapidly acting medication shown to decrease suicidality in adults in as short as hours or days, as opposed to weeks. The study design is a double-blind, randomized, active-control trial of adolescents (ages 13-18 years) with recent suicidal behaviors (suicide attempt or increased suicidal ideation). All participants must be receiving standard of care treatment which may range broadly from both outpatient and inpatient programs which include clinically indicated psychosocial and/or psychopharmacological treatments. Ketamine/midazolam treatment will occur twice weekly during the first two weeks of the study, followed by weekly assessments through week 12.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Zachary.Brown@UTSouthwestern.edu
• Be adolescents (aged 13-18 years);
• Have had a recent suicidal event (suicide attempt or significant suicidal ideation with a plan or intent warranting emergency evaluation or inpatient hospitalization within the past 90 days);
• Receiving standard of care treatment that includes clinically indicated psychosocial and/or psychopharmacological treatment;
• Have a current primary diagnosis of a depressive disorder based on the MINI-KID (other psychiatric disorders are acceptable, but must not be primary);
• Both participants and their designated caregiver must be able to complete assessments in English, as the rating scales vital to study efficacy and safety evaluations have not been validated in Spanish. (NOTE: Most potential participants ages 13 to 18 years old, as well as most of their parents, have a good working knowledge of English);
• Use effective method of contraception during and for 90 days following the end of treatment for female and male participants. Recommended methods of birth control are namely, consistent use of an approved hormonal birth control (pill/patches, rings), an intrauterine device (IUD), contraceptive injection, double barrier methods, sexual abstinence, or sterilization; Exclusion Criteria Study participants must not:
• Have a psychotic disorder, such as lifetime schizophrenia, or a pervasive or intellectual developmental disorder requiring substantial or very substantial support;
• Have current mania, hypomania, mixed episode, or obsessive-compulsive disorder;
• Have a primary diagnosis other than a depressive disorder;
• Have moderate to severe alcohol or substance use disorder within the past six months (based on MINI-KID); If there is a positive urine drug screen at screening, the urine drug screen will be repeated at each infusion visit. Positive urine drug screen will be reviewed by study physician and infusion will proceed as long as no safety risk was identified;
• If female, be pregnant, lactating, or nursing; Women of childbearing potential must have a negative urine pregnancy test prior to all infusions;
• Have unstable medical conditions (stable for less than 3 months) or with clinically significant laboratory values or an electrocardiogram (ECG) that would pose significant risk;
• Be at serious suicidal risk that cannot be managed in the outpatient setting;
• Have prior treatment for depression with or contraindications to ketamine, esketamine, or, midazolam;
• Treatment with medications that may alter pharmacokinetics of ketamine, including moderate-to-strong inhibitors or inducers of CYP3A4 and CYP2B6, is exclusionary. Regarding pharmacodynamic interactions, medications that may increase heart rate or blood pressure such as the ADHD stimulant medications will be permitted with last dose at least 24 hours prior to infusion. All concomitant medications will be evaluated by the study physician to determine if the type and dose of concomitant medication requires discontinuation and will be excluded if the concomitant medication could substantially increase the risk of study infusion. A complete list of medications that are Not Allowed is available in Appendix D of the protocol. The study team will not ask the participant to discontinue any treatment (except for not taking ADHD medications for 24 hours before study treatment) just for the sake of taking part in this study;
• Weigh >120 kilograms at baseline. If participants are enrolled but exceed 120 kilograms at any time during the treatment period, they will be removed from the treatment portion of the study.
CLOZAPINE Response in Biotype-1
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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Asha.Philip@UTSouthwestern.edu
Youth Depression and Suicide Research Network (YDSRN)
The objective of this study is to build the Texas Youth Depression and Suicide Research Network to support the development of a Network Participant Registry and characterization of systems and interventions to examine statewide population health outcomes. All 12-13 sites represented in the Texas Child Mental Health Care Consortium (https://www.utsystem.edu/pophealth/tcmhcc/) have been invited to participate in the Texas Youth Depression and Suicide Research Network as "Nodes." 12 Nodes have been selected for this project. Each Node has obtained support of senior institutional leadership including the department chair. Leadership from each Node provided input and edits in the study design process by committee, with a focus on the inclusion of the "end user" in design decisions. Nodes will work closely with the Network Hub leadership to recruit, monitor, and retain participants. This will require active engagement and sustained relationships with clinics within the academic medical center as well as clinics in the community (i.e., psychiatry, psychology, counselling).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Lynnel.Goodman@UTSouthwestern.edu
• Be 8 to 20 years of age;
• Have a positive screen for depression (e.g., based on PHQ-2 (score ≥3) and/or PHQ-A of 10 or greater, OR positive for suicidal ideation or behavior (e.g., based on CHRT-SR or PHQ-A item 9); OR be in treatment for depression;
• Be willing to provide consent/assent (parents/LAR/guardian or young adult participant, aged 18-20, must be willing to provide consent; youth, aged 8-17, must be willing to provide assent);
• Be able to speak English or Spanish sufficiently to understand the study procedures and provide written informed consent to participate in the study;
• Be willing to dedicate appropriate time to complete scheduled study assessments and measures (both parent/LAR/guardian and youth).
• Be able to provide a reliable means of contact.
• Have an acute medical or psychological condition(s) that that would, in the judgment of the study medical clinician, make participation difficult or unsafe;
• Have an acute medical or psychological condition(s) that would result in an inability to accurately complete study requirements (e.g., neurological conditions or significant neurodevelopmental concerns);
• Have active psychotic symptoms resulting in altered mental status and inability to provide assent or requiring immediate attention and/or higher level of intervention;
• Have a parent/LAR/guardian who is deemed cognitively unable to provide consent (if youth participant, aged 8-17).
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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ana.Arroyo@UTSouthwestern.edu
• Male or female adults aged 18 years or greater. There will be no upper age limit.
• 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.
• Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based criteria
• Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization.
• Able to understand and sign informed consent after the nature of the study has been fully explained
• Kidney transplant patients that are at least 6 month post-transplantation (3 months post-transplant, with at least another 3 months to confirm eGFR <45)
• Unable to understand or give informed consent.
• Unwilling or unable to participate in the protocol or comply with any of its components
• Receiving chronic dialysis
• Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than the upper limit of normal
• Terminal chronic obstructive pulmonary disease or cancer
• Presence of seizure disorder
• 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
• Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort.
• Use of medications known to cause QT prolongation on EKG
• Ongoing use of antidepressant medications for depression treatment
• Past treatment failure on bupropion
• Initiation of depression-focused psychotherapy in the 3 months prior to study entry
• Active alcohol or substance abuse or dependence that requires acute detoxification at study entry
• Present or past psychosis or Bipolar I or II disorder
• Dementia or a Mini-Mental State Examination score <23
• Active suicidal intent
• Pregnancy, lactation, or women of childbearing potential not willing to use adequate contraception
Metformin in Alzheimer's Dementia Prevention (MAP)
MAP will be a multisite phase II/III 1:1 randomized controlled trial (RCT) of long acting metformin (reduced mass Glucophage XR) vs. matching placebo in 326 men and women with early and late aMCI, without diabetes, not treated with metformin, overweight or obese, aged 55 years to 90 years. The RCT will last 18 months and have 4 visits: baseline, 6-months, 12-months, and 18-months. The RCT will be preceded by a screening phase followed by randomization and a titration period in which drug/placebo will be titrated from 500 mg a day (one tablet) to 2,000 mg a day (4 tablets), in increments of 500 mg (one tablet) every 10 days. Participants will remain in the RCT on the tolerated dose, and included in analyses on an intent to treat basis. We expect the attrition rate to be 10%/year. Neuropsychological battery, clinical interviews, physical exam, and phlebotomy will be conducted at baseline and every 6 months. Brain MRI will be conducted in approximately half of the participants (186) twice, at baseline, and after the last study visit at month 18. We will also conduct brain amyloid Positron Emission Tomography (PET) using 18F-Florbetaben, and tau PET using 18F-MK6240 in half of the participants at baseline and end of the RCT. The primary clinical outcome of the study will be changes in the Free and Cued Selective Reminding Test. The secondary endpoints are 1) changes in global cognitive performance, measured with the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC); 2) changes in neurodegeneration, ascertained as cortical thickness in areas affected by AD on brain MRI; 3) changes in cerebrovascular disease, ascertained as white matter hyperintensities (WMH) volume on brain MRI; 4) Changes in whole brain amyloid ß (Aß) SUVR and in incident amyloid positivity; 5) Changes in tau SUVR in a composite brain region comprising medial and inferolateral temporal cortex; 6) Changes in plasma AD biomarkers. The data coordinating center and Imaging Core is located at John Hopkins University. The PET coordinating center is located at UC-Berkeley. The Clinical Coordinating and Monitoring Center and the central laboratory will be located at Columbia. The Research pharmacy function will be shared by the University of Rochester, which will dispense randomization kits, and the University of Iowa, which will receive bulk metformin and identical matching placebo from EMD Serono.
Call 214-648-5005
studyfinder@utsouthwestern.edu, kyle.krautkramer@UTSouthwestern.edu
Suicide Treatment Alternatives for Teens (START)
Quasi-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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, AMY.CONGER@UTSouthwestern.edu
• Adolescents that are 12 through 17 years old (including 17 year olds who will turn 18 years old during the course of the study).
• Are brought to the Emergency Department (ED) due to suicidal thoughts or behaviors
• Require a higher level of care (OCIC or Inpatient) indicated by clinician determination and a CHRT-SR score of 15 to 52.
• The presence of a legal guardian
• Capable of giving signed informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Adolescents with suicidal thoughts that place themselves at a serious imminent risk of suicide based on clinical judgment.
• Adolescents who require 24 hour/day supervision but no adult can provide 24 hour/day supervision outside of the hospital
• Adolescents without the ability to read and answer survey questions
• Adolescents that are non-English speaking due to the scales and surveys that are used for this study only being available in English.
Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression
Treatment resistant depression remains a major problem for individuals and society. Surgical procedures may provide relief for some of these patients. The most frequently considered surgical approach is deep brain stimulation (DBS) of a part of the brain called the subcallosal cingulate region. However, the effectiveness and safety is not well established. The investigators will use a novel approach using advanced imaging technique (magnetic resonance tractography) to evaluate the feasibility and safety of this surgical approach. An innovative method for the definition of DBS target will be applied that redefines the concept of targeting as one of targeting a symptomatic network rather than a structural brain region using subject-based brain anatomy to define the target location. The correlation between imaging findings at baseline with the mood score changes at different time points of the study will be investigated.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hila.AbushSegev@UTSouthwestern.edu
• Pregnant or has plans to become pregnant in the next 36 months;
• Unable/unable to practice birth control through the period of randomization and withdrawal of therapy; * Subjects who have a history of a seizure disorder; * Subjects who will be exposed to diathermy; * Subjects who have any medical contraindications to undergoing DBS surgery (e.g. infection, coagulopathy, or significant cardiac or other medical risk factors for surgery); * Subjects with another implanted device such as a cardiac pacemaker, defibrillator or neurostimulator; * Subjects who have a history of hemorrhagic stroke; * Subjects who are unable to undergo MRI; * Subjects who are at increased risk of hemorrhage due to underlying medical conditions or medication.
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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Shuchi.Lakhanpal@UTSouthwestern.edu
• Men and women age 18-50 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)
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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Shuchi.Lakhanpal@UTSouthwestern.edu
• Women aged 40-67 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
• Vulnerable populations (e.g. pregnant/nursing, severe cognitive or intellectual impairment, incarcerated)
• Pregnancy (determined by urine pregnancy test), intending pregnancy or breast feeding
• Psychiatric disorder other than MDD that is acute and the primary focus of symptom burden or treatment.
• History of bipolar disorder or psychotic disorder
• Current substance use disorder
• Positive baseline urine drug screen of an illicit substance (in this study: opioids and cocaine,) with the exception of a medication used with a prescription (use of a detected substance that is used with a prescription, such as an opioid pain medication, is not necessarily exclusionary and will be based upon judgment of the PI, particularly in the cases of chronic opioid use). Participants who screen positive for marijuana will be offered a rescreen for eligibility at a later date.
• Current eating disorder
• Treatment resistant depression (failure of 2 adequate antidepressant trials or electroconvulsive therapy (ECT) during current episode; adequate antidepressant trials are defined as within the US FDA approved dosage for the medication and used for at least 6 weeks, with failure described by the patient as <50% improvement based on her subjective experience).
• High risk for suicidal acts including active suicidal ideation with plan and intent or > 2 suicide attempts in lifetime or any attempt in the past 6 months
• Use of selective estrogen-receptor modulators (SERMs), hormone replacement therapy, hormonal contraceptives (hormonal IUDs allowed), episodic sleep medications (chronic, regular, stable-dose benzodiazepines and hypnotics such as zolpidem, Sonata (Zaleplon), and Lunesta (Eszopiclone) OR sleep-seating antihistamines such as Unisom (Doxylamine succinate) or diphenhydramine allowed) within 2 weeks of the baseline visit and randomization. Antidepressants will be allowed for those participants who have been taking the antidepressant for 6 weeks with a stable dose for at least 4 weeks.
• Use of natural menopause and depression supplements, phytoestrogens, soy-based medications, steroids within 2 weeks of baseline visit and randomization.
• Use of any disallowed medications (specified in the Excluded Concomitant Medication section below).
• Women who have received a gonadal hormonal intervention within 1 month prior to study entry (stable thyroid medications are allowed).
• Not using a medically approved method of birth control, if sexually active and not 12 or more months since last menstrual period IUDs, condoms, abstinence are acceptable forms of contraception in this study; due to the possible interactions with the study medication, oral contraceptive pills will be prohibited.
• Uncontrolled hypertension (>160/95mmHg)
• Active coronary artery disease, atrial fibrillation, stroke, deep vein thrombosis, pulmonary embolism or blood clotting disorder
• Any severe, life threatening or unstable medical condition that, based on clinician-judgment, would make participation in the study unsafe or inappropriate
• Personal or first degree family history of known hormone sensitive tumors
• History of allergic reaction or side effects with prior pregnenolone use
• Clinically significant laboratory or physical examination findings
• Concurrent enrollment in another clinical trial Exclusion of Concomitant Medications:
• Selective estrogen-receptor modulators (SERMs)
• Hormone replacement therapy
• Hormonal contraceptives, excluding Mirena IUD or other IUD with localized progesterone
• Natural menopause or antidepressant supplements
• Episodic sleep medications (chronic, regular, stable-dose benzodiazepines and hypnotics such as zolpidem, Sonata (Zaleplon), and Lunesta (Eszopiclone) OR sleep-sedating antihistamines such as Unisom (Doxylamine succinate) or diphenhydramine allowed)
• Sub-therapeutic dosages of antidepressants used for other indications will be permissible with the exclusion of SSRIs, SNRIs, and Wellbutrin.
• Phytoestrogens
• Soy-based medications or supplements
Resilience in Adolescent Development (RAD)
The RAD study is a longitudinal study to prospectively characterize the biological mechanisms of resilience in adolescents and young adults at risk for developing depression. The study will capture biomarkers from the domains of socio-demographic and clinical data, cognitive and psychological assessments, fluid-based biomarkers, neuroimaging and EEG. Such biomarkers will compose a human biosignature of resilience and identify risk factors for depression, contributing to effective treatment selection or may represent moderators of response or non-response to treatments in subjects with depression. A cohort of 1,500 participants, age 10-24 will be recruited over a 10-year period. Participants will be followed for 10 years following an initial baseline visit. Study visits are conducted up to 4 times per year.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Yara.Alarcon-Furman@UTSouthwestern.edu
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.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Yara.Alarcon-Furman@UTSouthwestern.edu
• Male and female adult or youth aged 10 and older of any race or ethnicity.
• 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.
• A lifetime or a current diagnosis of a mood disorder based upon a semi-structured diagnostic interview.
• 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.
• Male and female adult or youth aged 10 and older of any race or ethnicity.
• 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.
• 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:
• History of schizophrenia, schizoaffective disorders or chronic psychotic disorders based upon a semi-structured diagnostic interview.
• Diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C (human immunodeficiency virus (HIV) testing is not required for this study).
• Unable to provide a stable home address and contact information.
• 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.
• 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:
• A lifetime or a current history of a mood disorder based upon a semi-structured diagnostic interview.
• Meets any exclusion criteria as part of the main D2K study interview.
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression (RECOVER)
Objectives of this study are to determine whether active VNS Therapy treatment is superior to a no stimulation control in producing a reduction in baseline depressive symptom severity, based on multiple depression scale assessment tools at 12 months from randomization.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Hila.AbushSegev@UTSouthwestern.edu
Developing an Intervention to Promote Lethal Means Safety in Suicidal Adolescents
Study Objective: to develop a phone-based intervention to aid parents of suicidal adolescents to adhere to lethal means safety. Lethal means counseling is the practice of educating patients and their families about limiting access to items that can be used to attempt suicide. Though lethal means counseling is standard practice in treating suicidal patients, there is little experimental literature related to its utilization across different providers and its efficacy. Further, there is a significant gap in the literature on lethal means counseling as it relates to adolescents. The proposed project will investigate a novel text message-based intervention aimed to promote lethal means safety.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Rebecca.Wildman@UTSouthwestern.edu
• Proficiency in spoken and written English
• Own cell phone that has internet capabilities
• Adolescent participants are patient's at Children's Health SPARC IOP (ages 12-17)
• Adult participants are parents and/or legal guardians of adolescent participants (ages 18+)
• Non-English speaking