Traumatic Brain InjuryPhase 2NCT05671692
Novel Intervention for Chronic Complex TBI in OEF/OIF/OND Veterans
A Phase 2 study testing Pregnenolone in people with Traumatic Brain Injury and TBI, run by Christine Marx, MD at 2 sites in United States.
Trial summary
The goal of this clinical trial is to compare pregnenolone and placebo (a placebo is a look-alike substance that contains no active drug) in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND)-Era Veterans with a history of chronic Traumatic Brain Injury (TBI). Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Traumatic Brain Injury, TBI
- What is being tested?
- Pregnenolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 2 sitesUnited States
- Study dates
- 6 Sep 2024to 30 Aug 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 21-65 years of age, any ethnic group, either sex.
- History of mild TBI since 2001 and service in the U.S. Military since 9/11/01 (OEF/OIF/OND era).
- We will adhere to the operational definition of mild TBI suggested by the World Health Organization Task Force (Holm et al 2005), with the exception of Glasgow Coma Scale score criteria (not available for these participants): a.) 1 or more of the following: confusion or disorientation, loss of consciousness for 30 minutes or less, post-traumatic amnesia for less than 24 hours, and/or other transient neurological abnormalities such as focal signs, seizure, and intracranial lesion not requiring surgery; Glasgow Coma Scale (GCS) score of 13-15 after 30 minutes post-injury or later upon presentation for health care (GCS unavailable). This WHO diagnostic definition of mild TBI is also consistent with the CDC Report to Congress on Mild TBI in the United States, September 2003 (specifically, altered consciousness attributable to the head injury [=transient confusion, disorientation or impaired consciousness] or self-reported loss of consciousness lasting 30 minutes or less).
- Ability to read/understand English and to participate fully in the informed consent process.
- No anticipated need to alter psychiatric or pain medications for duration of study involvement.
- No changes in psychotropic or behavioral interventions during the study or in the 2 weeks prior to study enrollment.
- Negative pregnancy test if female. Sexually active subjects are required to use a medically acceptable form of birth control if they are of childbearing potential and could become pregnant during the study.
Who cannot join
- Exclusionary criteria will diverge slightly from the above WHO definition of mild TBI and exclude participants who report a history of seizures for this investigation.
- Participants with current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern.
- Concomitant medications for co-occurring medical conditions are permissible for stable medical conditions that are reasonably well-controlled (for example, hypertension medications, statins, and oral hypoglycemic medications would generally be permissible if they appear to be effectively treating the underlying condition). Medications that could potentially confound study outcomes (for example, prednisone) are exclusionary.
- Participants who report a history of seizures, a history of stroke, a history of prostate cancer (or any other cancer other than non-melanoma skin cancer), a history of myocardial infarction, the presence of congestive heart failure, or any other serious health condition that would likely preclude safe study participation in the medical opinion of the PI or in consultation with the participant's PCP/other health care provider).
- Current DSM-5 diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition other than TBI.
- Female participants who are pregnant or breast-feeding.
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- Known allergy to study medication.
- Benzodiazepine or opioid use within the last 2 weeks is exclusionary.
- Substance use disorder (DSM-5), other than nicotine use disorder.
- Serious unstable medical illness. History of cerebrovascular accident, prostate, uterine or breast cancer. Medications to treat these conditions either acutely or chronically (for example, finasteride, tamoxifen, clopidogrel) are also exclusionary.
- Use of oral contraceptives or other hormonal supplementation such as estrogen or progesterone, as there is a theoretical risk that a metabolite of pregnenolone could potentially impact efficacy of oral contraceptives and estrogen replacement.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Duke University School of Medicine
Durham, North Carolina, 27705
Durham VA Health Care System
Durham, North Carolina, 27705
About this study
The goal of this clinical trial is to compare pregnenolone and placebo (a placebo is a look-alike substance that contains no active drug) in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND)-Era Veterans with a history of chronic Traumatic Brain Injury (TBI). The main questions it aims to answer are:
- Does pregnenolone improve psychological health, overall physical function, cognition, symptoms of PTSD, and pain more than placebo over the 8-week study period, and what is the most effective dose of the drug that is safe and well-tolerated?
- What are the biological effects of pregnenolone, and how do pregnenolone and other molecules change over the course of treatment? (and do pregnenolone and other molecules predict clinical improvement?)
Read more
Participants who are eligible and consent to participate in the study will:
- be randomized in a 1:1 ratio to take pregnenolone or placebo
- be given pregnenolone or placebo to take each day at home
- will participate in 6 visits over 11 weeks for tests, exams and procedures that are for study purposes (each visit will last 1.5 - 3 hours)
- be evaluated at each visit to determine if there are any bad reactions to the study drug and if study participation is still appropriate
- be financially compensated for their visit time and travel cost
- Conditions
- Traumatic Brain Injury, TBI
- Being tested
- Pregnenolone, Placebo
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregnenoloneDrug
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
PlaceboDrug
Same as active comparator, except placebo dispensed.
| Study group | Role | What they receive |
|---|---|---|
| Pregnenolone | Active comparator | Not described Receives: Drug: Pregnenolone |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in psychological health as measured by the Brief Symptom Inventory-18 (BSI)
The BSI-18 GSI summarizes a respondent's overall level of psychological distress. The score used in a normatively based T-score (range 1-100) calculated from the sum of responses. Higher scores are indicative of greater distress. The outcome measure is the change in scores before and after treatment (the baseline and Week 8 difference scores).
Measured: Baseline, week 8
Secondary outcomes (7)
Changes in physical health as measured by the 36-Item Short Form Health Survey (SF-36)
These data report changes in the mean scores in physical health symptoms using the Physical Health Summary sub score of the SF-36. The SF-36 is a health survey with an 8-scale profile embedded in 36 questions that measures components of health. Each item is scored on a 0 to 100 range, with the lowest and highest possible scores set at 0 and 100, respectively. All of these items are scored such that a high score defines a more favorable health state. Thus, increases in scores represent improvements relative to baseline.
Measured: Baseline, week 8
Changes in mental health as measured by the 36-Item Short Form Health Survey (SF-36)
These data report changes in the mean scores in mental health symptoms using the Mental Health Summary sub score of the SF-36. The SF-36 is a health survey with an 8-scale profile embedded in 36 questions that measures components of health. Each item is scored on a 0 to 100 range, with the lowest and highest possible scores set at 0 and 100, respectively. All of these items are scored such that a high score defines a more favorable health state. Thus, increases in scores represent improvements relative to baseline.
Measured: Baseline, week 8
Changes in cognition as measured by the Wechsler Adult Intelligence Scale (WAIS-IV)
WAIS-IV coding test is a valid and sensitive measure of cognitive dysfunction that correlates with functional outcomes. The participant is required to identify the symbols matched to numbers using a key and write in the symbol beneath the associated number. The total score ranges from 0 to 135 and is based on the total number of codes correctly completed over a 90-second time limit. Higher scores indicate better processing speed. Positive change from baseline indicates better processing speed.
Measured: Baseline, week 8
Changes in cognition as measured by the Stroop Color and Word Test (STROOP)
The Stroop is a neuropsychological test extensively used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus attribute, well-known as the Stroop Effect. The score for the Stroop Test is the number of correct responses provided in 45 seconds on each test condition: word reading, color naming, and inhibition. Scores range from 0 to no upper limit, with higher scores indicating better performance.
Measured: Baseline, week 8
Changes in PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5)
Post-Traumatic Stress Disorder (PTSD) symptoms will be evaluated by the Post-Traumatic Stress Disorder Checklist Scale-Version DSM 5 (PCL-5). This questionnaire contains twenty items to assess PTSD symptoms. A total score for symptom severity (0-80) can be obtained by summing the scores for each of the 20 items. Higher scores are indicative of greater symptomatology.
Measured: Baseline, week 8
Changes in depression symptoms as measured by the Beck Depression Inventory-II (BDI-II)
The BDI-II is a 21-item, self-report rating inventory that assesses symptoms of depression. Scores range from 0 (no depression) to 63 (severe depression). Higher scores indicate greater depression symptomatology.
Measured: Baseline, week 8
Changes in pain symptoms as measured by the Brief Pain Inventory (BPI)
The Brief Pain Inventory (BPI) is a self-reported scale that measures the severity of pain symptoms. The scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The Interference scores range from 0 (does not interfere) to 10 (completely interferes); there are 7 questions assessing the interference of pain. The outcome measure is the change in scores before and after treatment (the baseline and Week 8 difference scores). Higher scores are associated with greater pain.
Measured: Baseline, week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2023
- Study start6 Sep 2024
- Primary completion30 Aug 2026 (estimated)
- Study completion30 Aug 2026 (estimated)
Why it stopped: FDA partial clinical hold.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Christine Marx, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Christine Marx, MD, Duke University
- Investigators
- Chris Marx, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05671692
- Sponsor's protocol ID
- Pro00111732
- Status last verified
- May 2026
- First submitted
- 21 Dec 2022
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Per FITBIR policy on Data Sharing, we will submit all de-identified data to FITBIR after the completion of the study. All data are submitted in accord with applicable laws and regulations, and that the identities of research participants will not be disclosed to the FITBIR Informatics System. FITBIR Data Sharing Policy includes steps to protect the interests and privacy concerns of individuals, families, and identifiable groups who participate in TBI genetic and other research.
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Intervention for Chronic Complex TBI in OEF/OIF/OND Veterans
- ClinicalTrials.gov ID
- NCT05671692
- Acronym / sponsor ID
- Pro00111732
- Conditions
- Traumatic Brain Injury, TBI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: FDA partial clinical hold.
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Christine Marx, MDUniversity, hospital or other
- Study start
- 6 Sep 2024 (actual)
- Primary completion
- 30 Aug 2026 (estimated)
- Study completion
- 30 Aug 2026 (estimated)
- First posted
- 5 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to compare pregnenolone and placebo (a placebo is a look-alike substance that contains no active drug) in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND)-Era Veterans with a history of chronic Traumatic Brain Injury (TBI). The main questions it aims to answer are:
- Does pregnenolone improve psychological health, overall physical function, cognition, symptoms of PTSD, and pain more than placebo over the 8-week study period, and what is the most effective dose of the drug that is safe and well-tolerated?
- What are the biological effects of pregnenolone, and how do pregnenolone and other molecules change over the course of treatment? (and do pregnenolone and other molecules predict clinical improvement?)
Participants who are eligible and consent to participate in the study will:
- be randomized in a 1:1 ratio to take pregnenolone or placebo
- be given pregnenolone or placebo to take each day at home
- will participate in 6 visits over 11 weeks for tests, exams and procedures that are for study purposes (each visit will last 1.5 - 3 hours)
- be evaluated at each visit to determine if there are any bad reactions to the study drug and if study participation is still appropriate
- be financially compensated for their visit time and travel cost
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregnenolone | Active comparator | Drug: Pregnenolone |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 21-65 years of age, any ethnic group, either sex.
- History of mild TBI since 2001 and service in the U.S. Military since 9/11/01 (OEF/OIF/OND era).
- We will adhere to the operational definition of mild TBI suggested by the World Health Organization Task Force (Holm et al 2005), with the exception of Glasgow Coma Scale score criteria (not available for these participants): a.) 1 or more of the following: confusion or disorientation, loss of consciousness for 30 minutes or less, post-traumatic amnesia for less than 24 hours, and/or other transient neurological abnormalities such as focal signs, seizure, and intracranial lesion not requiring surgery; Glasgow Coma Scale (GCS) score of 13-15 after 30 minutes post-injury or later upon presentation for health care (GCS unavailable). This WHO diagnostic definition of mild TBI is also consistent with the CDC Report to Congress on Mild TBI in the United States, September 2003 (specifically, altered consciousness attributable to the head injury [=transient confusion, disorientation or impaired consciousness] or self-reported loss of consciousness lasting 30 minutes or less).
- Ability to read/understand English and to participate fully in the informed consent process.
- No anticipated need to alter psychiatric or pain medications for duration of study involvement.
Key exclusion criteria (11 listed)
- Exclusionary criteria will diverge slightly from the above WHO definition of mild TBI and exclude participants who report a history of seizures for this investigation.
- Participants with current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern.
- Concomitant medications for co-occurring medical conditions are permissible for stable medical conditions that are reasonably well-controlled (for example, hypertension medications, statins, and oral hypoglycemic medications would generally be permissible if they appear to be effectively treating the underlying condition). Medications that could potentially confound study outcomes (for example, prednisone) are exclusionary.
- Participants who report a history of seizures, a history of stroke, a history of prostate cancer (or any other cancer other than non-melanoma skin cancer), a history of myocardial infarction, the presence of congestive heart failure, or any other serious health condition that would likely preclude safe study participation in the medical opinion of the PI or in consultation with the participant's PCP/other health care provider).
- Current DSM-5 diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition other than TBI.
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 |
|---|---|---|
| PregnenolonePregnenolone 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 |
| PlaceboSame as active comparator, except placebo dispensed. | Drug | Placebo |
Primary outcome
Changes in psychological health as measured by the Brief Symptom Inventory-18 (BSI)
Time frame: Baseline, week 8
The BSI-18 GSI summarizes a respondent's overall level of psychological distress. The score used in a normatively based T-score (range 1-100) calculated from the sum of responses. Higher scores are indicative of greater distress. The outcome measure is the change in scores before and after treatment (the baseline and Week 8 difference scores).
7 secondary outcomes
Changes in physical health as measured by the 36-Item Short Form Health Survey (SF-36)
Time frame: Baseline, week 8
Changes in mental health as measured by the 36-Item Short Form Health Survey (SF-36)
Time frame: Baseline, week 8
Changes in cognition as measured by the Wechsler Adult Intelligence Scale (WAIS-IV)
Time frame: Baseline, week 8
Changes in cognition as measured by the Stroop Color and Word Test (STROOP)
Time frame: Baseline, week 8
Changes in PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5)
Time frame: Baseline, week 8
Changes in depression symptoms as measured by the Beck Depression Inventory-II (BDI-II)
Time frame: Baseline, week 8
Changes in pain symptoms as measured by the Brief Pain Inventory (BPI)
Time frame: Baseline, week 8
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Individual participant dataSharing planned: Yes. Per FITBIR policy on Data Sharing, we will submit all de-identified data to FITBIR after the completion of the study. All data are submitted in accord with applicable laws and regulations, and that the identities of research participants will not be disclosed to the FITBIR Informatics System. FITBIR Data Sharing Policy includes steps to protect the interests and privacy concerns of individuals, families, and identifiable groups who participate in TBI genetic and other research.
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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.
Chris Marx, MD principal investigator
Duke University
2 sites 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 Traumatic Brain Injury and TBI, run by Christine Marx, MD at 2 sites 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 7 inclusion and 11 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: paused, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Results are not available in the source record.
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?
Changes in psychological health as measured by the Brief Symptom Inventory-18 (BSI) (time frame: Baseline, 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 13 May 2026.