Posttraumatic Stress DisorderPhase 2NCT03799562
Neurosteroids for Treatment of PTSD in Veterans
A Phase 2 study testing Pregnenolone in people with Posttraumatic Stress Disorder, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Posttraumatic Stress Disorder
- What is being tested?
- Pregnenolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 97 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Jun 2019to 14 Jul 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Durham VA Medical Center, Durham, NC
Durham, North Carolina, 27705-3875
About this study
Official title: Neurosteroid Intervention for PTSD in Iraq/Afghanistan-era Veterans
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.
Read the detailed description
BACKGROUND: There is an acute and urgent need to develop new and effective posttraumatic stress disorder (PTSD) pharmacotherapies, as there are currently only two FDA-approved medications for the treatment of PTSD (both of which are from the same drug class and have shown only moderate effect sizes in FDA registration trials). Many Veterans with PTSD thus remain symptomatic despite the availability of these treatments, increasing the likelihood of receiving pharmacological treatment interventions for which there is little or no empirical evidence. Multiple national and VA working groups focusing on PTSD have identified the critical need to address the paucity of PTSD pharmacotherapies, and have strongly recommended more randomized clinical trials to evaluate possible effective pharmacological treatments. Both preclinical and clinical data suggest that reductions in neurosteroids are involved in the pathophysiology of PTSD, and that ameliorating these deficits could potentially be clinically therapeutic - the proposed investigation targeting a neurosteroid intervention for the treatment of PTSD could thus be a promising research avenue. The investigators therefore propose to conduct a randomized clinical trial (RCT) to determine the efficacy of a neurosteroid intervention (pregnenolone) for PTSD and commonly co-occurring disorders in Iraq/Afghanistan-era Veterans, an understudied cohort that may be less treatment-refractory.
METHODS: This study will be a 10-week randomized, placebo-controlled, double-blind clinical trial of pregnenolone or matching placebo in Veterans with PTSD. The trial will include a 2-week single-blind placebo lead-in phase followed by 8 weeks of study medication (placebo or pregnenolone). Forty-five subjects meeting DSM-5 criteria for PTSD (as measured by a CAPS-5 score of 30) will be randomized to receive pregnenolone, and 45 subjects meeting DSM-5 criteria for PTSD will be randomized to receive placebo. The primary outcome for this RCT will be changes in total CAPS-5 score at Visit 6 for this modified intent-to-treat sample. Secondary clinical outcomes for this RCT include changes in pain intensity and functional interference, as measured by the Brief Pain Inventory, Short Form (BPI-SF) and depression symptoms by the Hamilton-Depression Rating Scale (HAM-D). Blood samples will be collected for serum analysis at all study visits and frozen in a -80 degree freezer. Upon completion of the study, samples will be thawed and analyzed using Gas Chromatography/Mass Spectrometry for neurosteroid analyses and inflammatory markers will be quantified. Genetic analyses will be conducted to determine therapeutic response.
PREDICTED RESULTS: The investigators hypothesize that treatment with pregnenolone will be efficacious in Iraq/Afghanistan-era Veterans with PTSD, and will significantly reduce PTSD symptoms as assessed by the CAPS-5 (primary endpoint) compared to placebo. Secondary endpoints will include the assessment of conditions that frequently co-occur with PTSD; specifically, the investigators hypothesize that pregnenolone will also demonstrate efficacy for co-occurring chronic pain symptoms and depression symptoms. The investigators hypothesize that increases in pregnenolone and other neurosteroids (and decreases in inflammatory markers) will predict improvements in PTSD, depression, and chronic pain symptoms. The investigators also hypothesize that neurosteroids are dysregulated in PTSD, and that specific SNPs of genes coding for neurosteroidogenic enzymes will be associated with therapeutic response.
- Conditions
- Posttraumatic Stress Disorder
- Being tested
- Pregnenolone, Placebo
- Keywords
- Depression, Pain, Clinical Trial, Veteran, Supplement
- Medical subject headings
- Stress Disorders, Post-Traumatic, Depression, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregnenoloneDrug
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
PlaceboDrug
Participants received matching placebo medication using the identical number of capsules and frequency of medication as the experimental study medication
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Pregnenolone |
| Placebo | Placebo comparator | Matching placebo medication dispensed identically with the same number and frequency as the experimental arm Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Study drug onset to treatment week 8
Secondary outcomes (3)
Change From Baseline in Brief Pain Inventory, Short Form (Visit 6 - Baseline): Average Pain
The Brief Pain Inventory, Short Form (BPI-SF) is a self-reported scale that measures the severity of pain and the interference of pain on function. The scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain in past 24 hrs, least pain in past 24 hrs, average pain, and pain right now. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life.
Measured: 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
The Brief Pain Inventory, Short Form (BPI-SF) is a self-reported scale that measures the severity of pain and the interference of pain on function. The scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain in past 24 hrs, least pain in past 24 hrs, average pain, and pain right now. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life.
Measured: Study drug onset to treatment week 8
Change From Baseline in Hamilton-Depression Inventory (Visit 6 - Baseline)
The HAM-D measures the severity of depressive symptoms. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms.
Measured: Study drug onset to treatment week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2019
- Study start27 Jun 2019
- Primary completion14 Jul 2025
- Study completion14 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Posttraumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to receive the active study medication (pregnenolone) or placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Jennifer C Naylor, PhD, Principal investigator, Durham VA Medical Center, Durham, NC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03799562
- Sponsor's protocol ID
- MHBB-004-18S
- Other IDs
- I01CX001784-01
- Status last verified
- Aug 2026
- First submitted
- 3 Jan 2019
- Last updated
- 26 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurosteroid Intervention for PTSD in Iraq/Afghanistan-era Veterans
- ClinicalTrials.gov ID
- NCT03799562
- Acronym / sponsor ID
- MHBB-004-18S
- Conditions
- Posttraumatic Stress Disorder
- Keywords
- Depression, Pain, Clinical Trial, Veteran, Supplement
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 27 Jun 2019 (actual)
- Primary completion
- 14 Jul 2025 (actual)
- Study completion
- 14 Jul 2025 (actual)
- First posted
- 10 Jan 2019 (actual)
- Results
- Posted 26 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
BACKGROUND: There is an acute and urgent need to develop new and effective posttraumatic stress disorder (PTSD) pharmacotherapies, as there are currently only two FDA-approved medications for the treatment of PTSD (both of which are from the same drug class and have shown only moderate effect sizes in FDA registration trials). Many Veterans with PTSD thus remain symptomatic despite the availability of these treatments, increasing the likelihood of receiving pharmacological treatment interventions for which there is little or no empirical evidence. Multiple national and VA working groups focusing on PTSD have identified the critical need to address the paucity of PTSD pharmacotherapies, and have strongly recommended more randomized clinical trials to evaluate possible effective pharmacological treatments. Both preclinical and clinical data suggest that reductions in neurosteroids are involved in the pathophysiology of PTSD, and that ameliorating these deficits could potentially be clinically therapeutic - the proposed investigation targeting a neurosteroid intervention for the treatment of PTSD could thus be a promising research avenue. The investigators therefore propose to conduct a randomized clinical trial (RCT) to determine the efficacy of a neurosteroid intervention (pregnenolone) for PTSD and commonly co-occurring disorders in Iraq/Afghanistan-era Veterans, an understudied cohort that may be less treatment-refractory.
METHODS: This study will be a 10-week randomized, placebo-controlled, double-blind clinical trial of pregnenolone or matching placebo in Veterans with PTSD. The trial will include a 2-week single-blind placebo lead-in phase followed by 8 weeks of study medication (placebo or pregnenolone). Forty-five subjects meeting DSM-5 criteria for PTSD (as measured by a CAPS-5 score of 30) will be randomized to receive pregnenolone, and 45 subjects meeting DSM-5 criteria for PTSD will be randomized to receive placebo. The primary outcome for this RCT will be changes in total CAPS-5 score at Visit 6 for this modified intent-to-treat sample. Secondary clinical outcomes for this RCT include changes in pain intensity and functional interference, as measured by the Brief Pain Inventory, Short Form (BPI-SF) and depression symptoms by the Hamilton-Depression Rating Scale (HAM-D). Blood samples will be collected for serum analysis at all study visits and frozen in a -80 degree freezer. Upon completion of the study, samples will be thawed and analyzed using Gas Chromatography/Mass Spectrometry for neurosteroid analyses and inflammatory markers will be quantified. Genetic analyses will be conducted to determine therapeutic response.
PREDICTED RESULTS: The investigators hypothesize that treatment with pregnenolone will be efficacious in Iraq/Afghanistan-era Veterans with PTSD, and will significantly reduce PTSD symptoms as assessed by the CAPS-5 (primary endpoint) compared to placebo. Secondary endpoints will include the assessment of conditions that frequently co-occur with PTSD; specifically, the investigators hypothesize that pregnenolone will also demonstrate efficacy for co-occurring chronic pain symptoms and depression symptoms. The investigators hypothesize that increases in pregnenolone and other neurosteroids (and decreases in inflammatory markers) will predict improvements in PTSD, depression, and chronic pain symptoms. The investigators also hypothesize that neurosteroids are dysregulated in PTSD, and that specific SNPs of genes coding for neurosteroidogenic enzymes will be associated with therapeutic response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants will be randomized to receive the active study medication (pregnenolone) or placebo.
| Arm | Type | Receives |
|---|---|---|
| Pregnenolone | Experimental | Drug: PregnenolonePlacebo 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 |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo medication dispensed identically with the same number and frequency as the experimental arm |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
- No anticipated need to alter psychiatric medications for duration of study involvement
- Ability to participate fully in the informed consent process
Key exclusion criteria (21 listed)
- 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
- Serious unstable medical illness, such as:
- Medical conditions not well controlled will be excluded, at the discretion of the PI and Medical Team
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PregnenoloneParticipants 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 | Drug | Pregnenolone |
| PlaceboParticipants received matching placebo medication using the identical number of capsules and frequency of medication as the experimental study medication | Drug | Placebo |
Primary outcome
Change From Baseline in Clinician Administered PTSD Scale for DSM-5 (Visit 6 - Baseline)
Time frame: Study drug onset to treatment week 8
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.
3 secondary outcomes
Change From Baseline in Brief Pain Inventory, Short Form (Visit 6 - Baseline): Average Pain
Time frame: 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
Time frame: Study drug onset to treatment week 8
Change From Baseline in Hamilton-Depression Inventory (Visit 6 - Baseline)
Time frame: Study drug onset to treatment week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer C Naylor, PhD principal investigator
Durham VA Medical Center, Durham, NC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pregnenolone in people with Posttraumatic Stress Disorder, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Clinician Administered PTSD Scale for DSM-5 (Visit 6 - Baseline) (time frame: Study drug onset to treatment week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.