Using pregnenolone to treat depression in people with HIV

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This trial investigates the effects of pregnenolone, a neuroactive steroid, on brain function, inflammation, and depressive symptoms in individuals living with HIV who also experience depression. Participants will be randomly assigned to receive either pregnenolone or a placebo while continuing their current antidepressant medications. The study will involve behavioral assessments and brain imaging techniques, including magnetic resonance spectroscopy and functional MRI, to evaluate changes over an 8-week period. The researchers aim to determine if pregnenolone can improve brain activity and reduce inflammation associated with depression in this population.

Why it matters

Who can join: the full rules

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 it's running

• Massachusetts General Hospital
  Boston, Massachusetts, United States Recruiting

Study contacts

• Principal investigator: Shibani S. Mukerji, MD, PhD — Massachusetts General Hospital
• Study coordinator: Hemi Park, MPH
• Email: MGHSOOTHE@PARTNERS.ORG
• Phone: 857-282-3788

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.