Neurosteroids for Treatment of PTSD in Veterans

NCT03799562 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MHBB-004-18SI01CX001784-01
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

Brief Summary

This study seeks to determine if pregnenolone can improve symptoms of PTSD and other symptoms that commonly occur with PTSD in Iraq/Afghanistan-era Veterans. The total study duration for each participant is 10 weeks. Eligible Veterans with PTSD will receive either pregnenolone or placebo throughout the study duration and will complete mental and physical health assessments at each study visit. Eligible participants will attend 6 in-person study visits and receive several short "check-in" phone calls.

Conditions

Posttraumatic Stress Disorder

Keywords

Depression; Pain; Clinical Trial; Veteran; Supplement

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Clinician Administered PTSD Scale for DSM-5 (Visit 6 - Baseline)

  The CAPS is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview that can be used to make a diagnosis of PTSD and assess PTSD symptoms. It assesses the intensity and frequency of PTSD symptoms. Scores range from 0-80; higher score indicates greater severity.

  Study drug onset to treatment week 8

Secondary Outcomes (3)

• Change From Baseline in Brief Pain Inventory, Short Form (Visit 6 - Baseline): Average Pain

  Study drug onset to treatment week 8

• Change From Baseline in Brief Pain Inventory, Short Form (Visit 6 - Baseline): Average Interference Across 7 Types of Activity

  Study drug onset to treatment week 8

• Change From Baseline in Hamilton-Depression Inventory (Visit 6 - Baseline)

  Study drug onset to treatment week 8

Study Arms (2)

Pregnenolone

EXPERIMENTAL

Placebo lead in 14 DAYS, followed by Pregnenolone 50 mg BID x 14 DAYS, followed by Pregnenolone 150 mg BID x 14 DAYS, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial

Drug: Pregnenolone

Placebo

PLACEBO COMPARATOR

Matching placebo medication dispensed identically with the same number and frequency as the experimental arm

Drug: Placebo

Interventions

Pregnenolone DRUG

Participants received Pregnenolone 50 mg BID x 14 DAYS, followed by Pregnenolone 150 mg BID x 14 DAYS, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial

Pregnenolone

Placebo DRUG

Participants received matching placebo medication using the identical number of capsules and frequency of medication as the experimental study medication

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:

• At study outset: DSM-5 diagnosis of PTSD with CAPS-5 Total Score \>=30. Following protocol amendment effective 4/13/2023: criterion modified to require diagnosis of PTSD using the CAPS-5 definition, defined by the following: at least one Criterion B symptom, at least one Criterion C symptom, at least 2 Criterion D symptoms and at least 2 Criterion E symptoms. This thus replaced the firm cutoff of CAPS-5 Total Score \>=30.
• Females 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 pregnenolone
• Medical disorders that may preclude safe administration of pregnenolone or exacerbate PTSD symptoms
• Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern
• Prior suicide attempt history 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)
• Medical conditions not well controlled will be excluded, at the discretion of the PI and Medical Team
• antidepressant medications such as SSRIs, SNRIs, tricyclics, bupropion, mirtazapine, venlafaxine, and nefazodone
• mood stabilizers such as carbamazepine, divalproex, lamotrigine, topiramate
• atypical antipsychotics, and other agents including prazosin
• However, there may be no changes in psychotropic medications for PTSD 4 weeks prior to study randomization
• Benzodiazepine 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)

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

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Depression; Pain

Interventions

Pregnenolone

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; 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

Results Point of Contact

• Title: Jennifer C. Naylor, PhD
• Organization: VISN 6 MIRECC, U.S. Department of Veterans Affairs, Durham VA Healthcare System

jennifer.naylor2@va.gov

(919) 286-0411

Study Officials

• Jennifer C Naylor, PhD

  Durham VA Medical Center, Durham, NC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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. Prior to finalization of data collection and cleaning of the clinical study database, 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: January 3, 2019
• First Posted: January 10, 2019
• Study Start: June 27, 2019
• Primary Completion: July 14, 2025
• Study Completion: July 14, 2025
• Last Updated: August 26, 2026
• Results First Posted: August 26, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)