HIV Clinical Trial
— SOOTHEOfficial title:
In Vivo Targeting of Neuroactive Steroid and Immune Networks for Depression in People Living With HIV
This study will determine the effects of pregnenolone on brain function, inflammation and depressive symptoms in people with HIV who have depression. Participants in this study will receive a pill of either pregnenolone or placebo, and can stay on their current antidepression medications. Brain imaging and behavioral assessments will be performed during the study.
Status | Recruiting |
Enrollment | 120 |
Est. completion date | January 31, 2028 |
Est. primary completion date | June 30, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 85 Years |
Eligibility | Inclusion Criteria: - 18-85 years - HIV-1 viral load <200 copies/mL on antiretroviral therapy (ART) at screening visit - Center for Epidemiological Studies - Depression (CES-D) score = 20 Exclusion Criteria: - Contraindication to magnetic resonance imaging (MRI) or poor-quality baseline MRI preventing image analyses as determined by radiologist assessment - Recent severe infections including opportunistic infections, active bacterial, mycobacterial, fungal, or certain viral infections - Vulnerable populations (e.g., pregnant/nursing, severe cognitive or intellectual impairment, incarcerated) - Use of cobicistat or ritonavir - High risk for suicide (active suicidal ideation (SI) with plan/intent as assessed by using the Columbia Suicide Severity Rating (C-SSRS) or > 2 attempts in lifetime or any in the past 6 months) or expresses homicidal ideation necessitating clinical intervention or representing an imminent concern - Any severe (life-threatening or unstable) medical condition as determined by clinician assessment - Blood pressure, with the lowest reading taken after three repeat readings during screening visit, = 160 mmHg systolic OR = 95 mmHg diastolic or other life-threatening vital signs as determined by clinician assessment - Clinically significant abnormalities in physical examination or ECG that would interfere with study participation - Decompensated cirrhosis, active liver inflammation (alanine aminotransferase (ALT)/aspartate aminotransferase (AST) = 5 times the upper limit of normal) or unsuppressed viral hepatitis B or C infection - Severe renal disease (estimated glomerular filtration rate = 30 mL/min/1.73m2) - Seizure disorder requiring antiepileptic treatment - History of allergic reaction or side effects with prior pregnenolone use - Currently using testosterone enanthate, testosterone cypionate, and specific preparations containing estrogen. Other forms of exogenous sex steroid hormones will be evaluated at the discretion of the PI and/or clinical delegates. - Currently using systemic immunosuppressive agents, including corticosteroids, chemotherapy, or specific immunomodulating agents, such as monoclonal antibodies and TNF-inhibitors - Excessive alcohol or other substances use that would interfere with classification of major depression disorder, study procedures and/or follow-up - Current diagnosis of bipolar disorder - Diagnosis of a psychotic disorder (current or lifetime) - Diagnosis of schizophrenia (current or lifetime) - <70% adherence to study drug prior to randomization - Inability to swallow pills/capsules - Not able to complete neuropsychological testing in English - Concurrent participation in another interventional trial, except for lifestyle and device studies (For vaccination studies, individuals in the observation period are not exclusionary. Other interventions will be evaluated at the discretion of the PI and/or clinical delegates.) |
Country | Name | City | State |
---|---|---|---|
United States | Massachusetts General Hospital | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Massachusetts General Hospital | Institute for Medical Research, Inc., National Institute of Mental Health (NIMH) |
United States,
Mukerji SS, Misra V, Lorenz DR, Chettimada S, Keller K, Letendre S, Ellis RJ, Morgello S, Parker RA, Gabuzda D. Low Neuroactive Steroids Identifies a Biological Subtype of Depression in Adults with Human Immunodeficiency Virus on Suppressive Antiretroviral Therapy. J Infect Dis. 2021 May 20;223(9):1601-1611. doi: 10.1093/infdis/jiaa104. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Gamma-aminobutyric acid (GABA) Concentration | Comparison between Pregnenolone and Placebo Groups of Left Insular Cortex GABA Concentration, Adjusted for Baseline. | Day 14, Day 56 | |
Secondary | Center for Epidemiological Studies-Depression (CES-D; scores range from 0 (no symptoms) to 60 (maximum severity of depressive symptoms)) | Comparison of Percentage of Pregnenolone and Placebo Groups Showing Clinical Improvement of Depression at Study End. The revised CES-D is administered, and the total score is calculated by adding the responses to the 20 questions. | Day 0, Day 14, Day 56 | |
Secondary | CD14+CD16+ Monocytes | Comparison of the Percentage of CD14+CD16+ Monocytes Over Time Adjusted for Baseline Between Pregnenolone and Placebo Groups | Day 0, Day 14, Day 28, Day 56 | |
Secondary | GABA Concentration in Responders | Comparison of Baseline Left Insular Cortex GABA and Pregnenolone Between Participants in Pregnenolone Group with Clinical Improvement Compared to Clinical Non-Improvers in Pregnenolone Group | Day 0, Day 14, Day 56 | |
Secondary | Adverse Events | Comparison of the Incidence and Severity of Adverse Events Between Pregnenolone and Placebo Groups | Day 14, Day 56 | |
Secondary | Dose Modifications | Comparison of Dose Modifications Required Between Pregnenolone and Placebo Groups | Day 14, Day 56 |
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