A New Intervention to Improve Function in Veterans With Anxiety and Depression

NCT06188923 | Recruiting Phase 2 FDA Drug

• 1 other identifier: D4287-R
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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

Keywords

pregnenolone; anxiety; depression; pain; sleep

Outcome Measures

Primary Outcomes (1)

• The World Health Organization disability assessment schedule II (WHODAS-2)

  The WHODAS-II is an instrument developed by the World Health Organization to assess behavioral limitations and restrictions regarding participation in specific activity domains experienced by an individual independent of their medical diagnosis. The conceptual frame of reference of this instrument is the International Classification of Functioning, Disability, and Health (ICF). Specifically, the instrument is a 36-item, generic, multidimensional questionnaire designed to evaluate the functioning of the individual in six activity domains (i.e., understanding and communicating, getting around, self-care, getting along with people, life activities, and participation in society). The 12-item WHODAS 2.0 score range from 12 to 60, where higher scores indicate higher disability or loss of function.

  Change from baseline at 10 weeks

Secondary Outcomes (3)

• Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS)

  Change from baseline at 10 weeks

• Brief Pain Inventory, Second Edition (BPI-II)

  Change from baseline at 10 weeks

• Pittsburgh Sleep Quality Index (PSQI)

  Change from baseline at 10 weeks

Study Arms (2)

Pregnenolone

ACTIVE COMPARATOR

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.

Drug: Pregnenolone

Placebo

PLACEBO COMPARATOR

Same as active comparator, except placebo dispensed

Drug: Placebo

Interventions

Pregnenolone DRUG

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.

Pregnenolone

Placebo DRUG

Same as active comparator, except placebo dispensed

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705-3875, United States

RECRUITING

MeSH Terms

Conditions

Anxiety Disorders; Depression; Pain

Interventions

Pregnenolone

Condition Hierarchy (Ancestors)

Mental Disorders; Behavioral Symptoms; Behavior; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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

Study Officials

• Jennifer C Naylor, PhD

  Durham VA Medical Center, Durham, NC

  PRINCIPAL INVESTIGATOR

• Christine E. Marx, MD MA

  Durham VA Medical Center, Durham, NC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer C Naylor, PhD

CONTACT

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

Christine E Marx, MD MA

CONTACT

(919) 286-0411; christine.marx@va.gov

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 with the exception of the research pharmacist.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive the active study medication (pregnenolone) or placebo.

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 3, 2024
• Study Start: August 14, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)