Clinical trial NCT05671692: Novel Intervention for Chronic Complex TBI in OEF/OIF/OND Veterans
Official title: Novel Intervention for Chronic Complex TBI in OEF/OIF/OND Veterans
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Traumatic Brain Injury
TBI
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2023-01-05
Enrollment: 108
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. 21-65 years of age, any ethnic group, either sex.
2. History of mild TBI since 2001 and service in the U.S. Military since 9/11/01 (OEF/OIF/OND era).
3. 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).
4. Ability to read/understand English and to participate fully in the informed consent process.
5. No anticipated need to alter psychiatric or pain medications for duration of study involvement.
6. No changes in psychotropic or behavioral interventions during the study or in the 2 weeks prior to study enrollment.
7. 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.

Exclusion Criteria:

1. 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.
2. Participants with current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern.
3. 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.
4. 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).
5. Current DSM-5 diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition other than TBI.
6. Female participants who are pregnant or breast-feeding.
7. Known allergy to study medication.
8. Benzodiazepine or opioid use within the last 2 weeks is exclusionary.
9. Substance use disorder (DSM-5), other than nicotine use disorder.
10. 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.
11. 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.

Primary outcomes:
measure: Changes in psychological health as measured by the Brief Symptom Inventory-18 (BSI)
timeFrame: Baseline, week 8
Secondary outcomes:
measure: Changes in physical health as measured by the 36-Item Short Form Health Survey (SF-36)
timeFrame: Baseline, week 8
measure: Changes in mental health as measured by the 36-Item Short Form Health Survey (SF-36)
timeFrame: Baseline, week 8
measure: Changes in cognition as measured by the Wechsler Adult Intelligence Scale (WAIS-IV)
timeFrame: Baseline, week 8
measure: Changes in cognition as measured by the Stroop Color and Word Test (STROOP)
timeFrame: Baseline, week 8
measure: Changes in PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5)
timeFrame: Baseline, week 8
measure: Changes in depression symptoms as measured by the Beck Depression Inventory-II (BDI-II)
timeFrame: Baseline, week 8
measure: Changes in pain symptoms as measured by the Brief Pain Inventory (BPI)
timeFrame: Baseline, week 8
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Durham
country: United States
facility: Durham VA Health Care System
state: North Carolina
Study officials:
affiliation: Duke University
name: Chris Marx, MD
role: PRINCIPAL_INVESTIGATOR
References: