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Allopregnanolone for Chronic Complex Traumatic Brain Injury

This study is testing if allopregnanolone (ALLO), a natural brain chemical, can help reduce depression and pain in people who have had a mild traumatic brain injury (TBI). Researchers believe ALLO might help because levels of it are often lower in people with TBI, depression, and pain. You could be eligible if you are between 21 and 62 years old, served in the U.S. Military since 9/11/01, and have a history of mild TBI with ongoing depression and pain. The study will compare two different doses of ALLO to a placebo (an inactive substance). Success would mean that ALLO helps improve depression and pain symptoms. The current status of this study is unclear.

Study design
This interventional study plans to enroll 132 participants. Participants will be randomly assigned to receive either a placebo, a lower dose of ALLO, or a higher dose of ALLO.
What's involved
You would receive an intravenous (IV) infusion of either ALLO or placebo. Behavioral assessments will be done during the infusion, after the infusion is tapered, and at 24 hours, 7 days, and 14 days post-infusion.
Compensation
Not stated in the trial record.
Follow-up
Your progress will be monitored for 14 days after the infusion, with assessments at 6 hours, 24 hours, 7 days, and 14 days.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT04003285

Allopregnanolone in Chronic Complex Traumatic Brain Injury

Not Yet Recruiting
PHASE2Ages 21–62InterventionalTreatment
VA Office of Research and Development
~132 participants
Updated 2026-09-08 on ClinicalTrials.gov
What's tested:PlaceboAllopregnanolone

At a glance

Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Brief Pain Inventory, Short Form (BPI-SF) Change
Measured over 6 hours, 24 hours, 7 days, and 14 days
+1 more outcome measured

Conditions

Traumatic Brain Injury (TBI)

Explore related trials

DepressionPainTraumatic Encephalopathy

NCT04003285

Where you'd take part

This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • Durham VA Medical Center, Durham, NC

    Durham, North Carolinastudy coordinator listed

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Christine E. Marx, MD MA · PRINCIPAL_INVESTIGATOR · Durham VA Medical Center, Durham, NC

Who to contact

Christine E Marx, MD MA
[email protected]
(919) 286-0411 · ext. 5112
Email the study team

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Eligibility criteria

Inclusion

Any ethnic group
History of mild traumatic brain injury (TBI) since 2001 and service in the U.S. Military since 9/11/01 (OEF/OIF/OND era)
The investigators will adhere to the operational definition of mild TBI suggested by the World Health Organization Task Force, with the exception of seizure and Glasgow Coma Scale score criteria (not available for these participants) with 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, and intracranial lesion not requiring surgery
Ability to participate fully in the informed consent process
Hamilton Depression Rating Scale (HDRS) score 14 (HAM-D range for moderate depression=14-18)
Participants will meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for major depressive disorder (by SCID)
The presence of psychotic features will be exclusionary
Single episodes or recurrent episodes will be permissible for study entry (the investigators will examine treatment responses in those who have had single depressive episodes versus those who have had multiple depressive episodes in exploratory sensitivity analyses
BPI (Brief Pain Inventory, Short Form) 'current' pain intensity rating item score 4 (scale of 0-10)
Pain must be musculoskeletal in nature
No anticipated need to alter psychiatric medications for 14-day duration of study involvement
No changes in psychotropic or behavioral interventions during the study or in the 2 weeks prior to study enrollment
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

Exclusion

Participants with current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern
Medications that could potentially confound study outcomes (for example, prednisone) are exclusionary
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
Benzodiazepine, barbiturate, or opioid use within the last 2 weeks is exclusionary
Substance use disorder (DSM-5), other than nicotine use disorder
A serious medical illness, defined as an illness that requires hospitalization for additional care at the time of screening or one that has required hospitalization in the last month.
Any co-occurring medical illness should have a history of stable outpatient management
Report of 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 Primary Care Provider (PCP)/other health care provider
Use of oral contraceptives, a hormone-releasing IUD, or other hormonal supplementation such as estrogen or progesterone, as there is a theoretical risk that a metabolite such as ALLO could potentially impact efficacy of oral contraceptives or estrogen replacement

What this trial measures

  • Brief Pain Inventory, Short Form (BPI-SF) Change6 hours, 24 hours, 7 days, and 14 days

    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, least pain, average pain in the past 24 hours, 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.

  • Hamilton-Depression Inventory (HAM-D) Change6 hours, 24 hours, 7 days, and 14 days

    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.