Novel Intervention for Chronic Complex TBI in OEF/OIF/OND Veterans

NCT05671692 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: Pro00111732
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 2

Brief 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). 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

Conditions

Traumatic Brain Injury; TBI

Outcome Measures

Primary Outcomes (1)

• 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).

  Baseline, week 8

Secondary Outcomes (7)

• Changes in physical health as measured by the 36-Item Short Form Health Survey (SF-36)

  Baseline, week 8

• Changes in mental health as measured by the 36-Item Short Form Health Survey (SF-36)

  Baseline, week 8

• Changes in cognition as measured by the Wechsler Adult Intelligence Scale (WAIS-IV)

  Baseline, week 8

• Changes in cognition as measured by the Stroop Color and Word Test (STROOP)

  Baseline, week 8

• Changes in PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5)

  Baseline, week 8

Study Arms (2)

Pregnenolone

ACTIVE COMPARATOR

Drug: Pregnenolone

Placebo

PLACEBO COMPARATOR

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

You may qualify if:

• 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.

You may not qualify if:

• Participants with current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern.
• 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.
• Known allergy to study medication.
• Substance use disorder (DSM-5), other than nicotine use disorder.
• 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.

Sponsors & Collaborators

• Christine Marx, MD: lead

Study Sites (2)

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

Durham VA Health Care System

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Pregnenolone

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

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

• Chris Marx, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 5, 2023
• Study Start: September 6, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: January 22, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: A contribution will be submitted after study completion and will remain in the FITBIR database indefinitely.
• Access Criteria: Only individuals with a FITBIR account who have submitted a Data Access Request that has been reviewed by the Data Access Quality Committee will be able to view the data.

Locations

US (2)