Recruiting
Phase 2

Neuroactive Steroid

Sponsor:

Massachusetts General Hospital

Code:

NCT05570812

Conditions

Major Depressive Disorder

Anxiety Depression

HIV

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Placebo

Pregnenolone

Study Details

Brief summary:

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.

Conditions

Major Depressive Disorder

Anxiety Depression

HIV

Study ID

NCT05570812

Start date

Mar 3, 2023

Status verified date

Sep, 2025

Completion date

Jan 31, 2028

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.)

Study Design

Enrollment

120 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Placebo

Participants will be on the following dosage schedule:

50 mg daily for 2 weeks, THEN 100 mg daily for 1 week, THEN 250 mg daily for 1 week, THEN 500 mg daily for 4 weeks

experimental: Pregnenolone

Participants will be on the following dosage schedule:

50 mg daily for 2 weeks, THEN 100 mg daily for 1 week, THEN 250 mg daily for 1 week, THEN 500 mg daily for 4 weeks

Interventions

Placebo

(4-week ramp, 4-week steady dosing)

Pregnenolone

(4-week ramp, 4-week steady dosing)

Primary outcome measure

  • Gamma-aminobutyric acid (GABA) Concentration [ Time Frame: Day 14, Day 56 ]

Central Contacts and Locations

Central contacts

Hemi Park, MPH

857-282-3788MGHSOOTHE@PARTNERS.ORG

Shibani S. Mukerji, MD, PhD

857-282-9950SMUKERJI@MGB.ORG

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator:

Shibani Mukerji, MD, PhD

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Sep 12, 2025

Last verified

Sep, 2025

Keywords

  • HIV
  • Depression
  • Neuroactive Steroid
  • Pregnenolone

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2025-09-12.