NCT05570812 · Massachusetts General Hospital
Neuroactive Steroid to Treat Depressed Mood: A Trial for People With HIV
(SOOTHE)
What this study is about
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.
View original scientific description
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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, or estrogen containing preparations that significantly increase systemic estrogen levels, including but not limited to oral and transdermal forms of estrogen. All 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.)
Where
- Boston, Massachusetts
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Sep 12, 2025 · Source of record for eligibility and locations