Using pregnenolone to treat PTSD in veterans

Neurosteroid Intervention for PTSD in Iraq/Afghanistan-era Veterans

Phase 2 Interventional VA Office of Research and Development · NCT03799562

This study is testing if a medication called pregnenolone can help veterans with PTSD feel better over 10 weeks compared to a placebo.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment90 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorVA Office of Research and Development Federal
Locations1 site (Durham, North Carolina)
Trial IDNCT03799562 on ClinicalTrials.gov

What this trial studies

This study investigates the efficacy of pregnenolone, a neurosteroid, in alleviating symptoms of Posttraumatic Stress Disorder (PTSD) among Iraq/Afghanistan-era Veterans. Over a 10-week period, eligible participants will be randomly assigned to receive either pregnenolone or a placebo, with regular mental and physical health assessments conducted during in-person visits and check-in phone calls. The study aims to address the urgent need for new pharmacotherapies for PTSD, as current treatments have shown limited effectiveness. By focusing on neurosteroids, the research seeks to explore a novel therapeutic approach for this underserved population.

Who should consider this trial

Good fit: Ideal candidates for this study are Iraq/Afghanistan-era veterans diagnosed with PTSD who meet specific inclusion criteria.

Not a fit: Patients with a history of allergy to pregnenolone or serious unstable medical illnesses may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new and effective treatment option for veterans suffering from PTSD.

How similar studies have performed: While there is limited research on neurosteroids for PTSD, the approach is considered promising based on preclinical and clinical data suggesting their potential therapeutic effects.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* DSM-5 diagnosis of PTSD with CAPS-5 Total Score 3
* 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

Exclusion Criteria:

* 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
* Standard pharmacological interventions for PTSD will not be exclusionary, including, but not limited to:

  * 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)
* Initiation or change in psychotherapy within 3 months of randomization

  * i.e., psychotherapy must be stable for 3 months prior to study start
* Participants on hormonal therapies such as finasteride or hormonal birth control
* Female participants who are pregnant or breast-feeding
* As indicated by the DSM-5, moderate or severe Substance Use Disorders (excluding caffeine and tobacco) within 1 month of study entry

  * Mild Alcohol Use Disorder is not exclusionary, at the judgment of the PI and her medical team

Where this trial is running

Durham, North Carolina

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Posttraumatic Stress DisorderDepressionPainClinical TrialVeteranSupplement
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.