Neuroactive Steroid to Treat Depressed Mood: A Trial for People With HIV

NCT05570812 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2022P0019411R01MH131194-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Keywords

HIV; Depression; Neuroactive Steroid; Pregnenolone

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Center for Epidemiological Studies-Depression (CES-D; scores range from 0 (no symptoms) to 60 (maximum severity of depressive symptoms))

  Day 0, Day 14, Day 56

• CD14+CD16+ Monocytes

  Day 0, Day 14, Day 28, Day 56

• GABA Concentration in Responders

  Day 0, Day 14, Day 56

• Adverse Events

  Day 14, Day 56

• Dose Modifications

  Day 14, Day 56

Study Arms (2)

Placebo

EXPERIMENTAL

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

Drug: Placebo

Pregnenolone

EXPERIMENTAL

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

Drug: Pregnenolone

Interventions

Placebo DRUG

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

Placebo

Pregnenolone DRUG

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

Also known as: Neuroactive steroid

Pregnenolone

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years
• HIV-1 viral load \<200 copies/mL on antiretroviral therapy (ART) at screening visit
• Center for Epidemiological Studies - Depression (CES-D) score ≥ 20

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Institute of Mental Health (NIMH): collaborator
• Institute for Medical Research, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 32157292 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Pregnenolone; Neurosteroids

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Study Officials

• Shibani S. Mukerji, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hemi Park, MPH

CONTACT

857-282-3788; MGHSOOTHE@PARTNERS.ORG

Shibani S. Mukerji, MD, PhD

CONTACT

857-282-9950; SMUKERJI@MGB.ORG

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a randomized, double-blind, placebo-controlled trial. All roles will be masked except the research pharmacist and statistician.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Model Details: Participants will be randomized to receive oral pregnenolone or placebo.

Study Record Dates

• First Submitted: October 4, 2022
• First Posted: October 7, 2022
• Study Start: March 3, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)