Recruiting
Phase 2

Pregnenolone

Sponsor:

VA Office of Research and Development

Code:

NCT06188923

Conditions

Anxiety and Depression

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Pregnenolone

Placebo

Study Details

Brief summary:

Anxiety and depression symptoms occur at high rates in Veteran populations and can significantly impact function, compromising the ability to work and to successfully form and maintain valued relationships. Several other symptoms commonly occur with anxiety and depression, including poor sleep quality and chronic pain. Since all these symptoms frequently occur together, they may have a common underlying biological basis. A single medication that could effectively treat all these symptoms would be ideal. Converging data suggest that pregnenolone is a promising pharmacological agent for treating multiple psychiatric symptoms and functional impairment. The investigators thus propose to conduct a clinical trial of pregnenolone in Veterans with anxiety and depression symptoms. Pregnenolone has minimal side effects, and the prior research demonstrates that pregnenolone is well-tolerated by Veterans. Treatment with pregnenolone could thus be an efficacious new therapeutic for Veterans experiencing depression, anxiety, poor sleep quality and chronic pain conditions.

Conditions

Anxiety and Depression

Study ID

NCT06188923

Start date

Aug 14, 2025

Status verified date

Jul, 2026

Completion date

Sep 30, 2028

Anticipated

Primary completion date

Jun 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Veterans enrolled for care at the Durham VAHCS
  • Veterans who score a minimum score of 20 or higher (moderate symptoms) on the PHQ-ADS (Kroenke et al 2017)
  • Oral pregnenolone could reduce the effectiveness of oral contraceptives, thus women will be required to use a medically and study-approved contraceptive or otherwise not be of child-bearing potential. Birth control methods must be non-hormonal
  • No anticipated need to alter psychiatric medications for duration of study involvement
  • Ability to participate fully in the informed consent process

Exclusion Criteria:

  • History of allergy to PREG
  • Medical disorders that may preclude safe administration of PREG or exacerbate mental or physical health symptoms
  • PTSD diagnosis, as per the PCL-5, scores of 38 or higher
  • Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern

  • Prior attempts or suicidal ideation that does not require clinical intervention or represent an imminent concern is permitted
  • Serious unstable medical illness, such as history of cerebrovascular accident, prostate, uterine or breast cancer, others (at the discretion of the PI and medical oversight team)
  • Standard pharmacological interventions for mental health disorders will not be exclusionary; however, there may be no changes in psychotropic medications for mental or physical health conditions 4 weeks prior to study randomization
  • Benzodiazepine or opioid use
  • Current diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition other than mild TBI (assessed at screening)
  • Initiation or change in psychotherapy within 3 months of randomization (i.e., psychotherapy must be stable for 3 months prior to study start
  • Due to lack of safety data in pregnant and breast-feeding women, female participants who are pregnant or breast-feeding will be excluded
  • As indicated by the DSM-5, moderate or severe Substance Use Disorders (excluding caffeine and tobacco) within 1 month of study entry

Study Design

Enrollment

84 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Pregnenolone

Pregnenolone 250 mg BID x 14 DAYS, followed by Pregnenolone 500 mg BID x 14 DAYS, followed by Pregnenolone 1000 mg BID x thereafter for the remainder of the 8-week trial.

placebo comparator: Placebo

Same as active comparator, except placebo dispensed

Interventions

Pregnenolone

Pregnenolone 250 mg BID x 14 DAYS, followed by Pregnenolone 500 mg BID x 14 DAYS, followed by Pregnenolone 1000 mg BID x thereafter for the remainder of the 8-week trial.

Placebo

Same as active comparator, except placebo dispensed

Primary outcome measure

  • The World Health Organization disability assessment schedule II (WHODAS-2) [ Time Frame: Change from baseline at 10 weeks ]

Central Contacts and Locations

Central contacts

Jennifer C Naylor, PhD

(919) 286-0411jennifer.naylor2@va.gov

Locations

Durham VA Medical Center, Durham, NC

Recruiting

Durham, North Carolina, United States, 27705-3875

Contacts

Jennifer C Naylor, PhD

919-286-0411jennifer.naylor2@va.gov

Principal Investigator:

Christine E. Marx, MD MA

More Information

Sponsor

VA Office of Research and Development

Last update posted

Jul 7, 2026

Last verified

Jul, 2026

Keywords

  • pregnenolone
  • anxiety
  • depression
  • pain
  • sleep

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by VA Office of Research and Development on 2026-07-07.