Traumatic Brain Injury (TBI)Phase 2ALLONCT04003285
Allopregnanolone in Chronic Complex Traumatic Brain Injury
A Phase 2 study testing Allopregnanolone in people with Traumatic Brain Injury (TBI), run by VA Office of Research and Development at 1 site in United States.
Trial summary
This study will determine if allopregnanolone (ALLO) improves depression and pain symptoms in patients who have a history of mild traumatic brain injury (TBI) [primary endpoints]. The investigators will also determine if ALLO improves functional outcome [secondary endpoint]. Read more about this study
- Who is it for?
- Ages 21 to 62 years
- Conditions the study is for
- Traumatic Brain Injury (TBI)
- What is being tested?
- Allopregnanolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 132 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2026to 1 Jun 2027
- Phase
- Phase 2
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 62 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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 traumatic brain injury (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
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- 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 principal investigator (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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Durham VA Medical Center, Durham, NC
Durham, North Carolina, 27705-3875
Christine E Marx, MD MA, (919) 286-0411 ext. 5112, christine.marx@va.gov
Christine E. Marx, MD MA
About this study
Official title: Novel Regenerative Therapeutic in Chronic Complex TBI
This study will determine if allopregnanolone (ALLO) improves depression and pain symptoms in patients who have a history of mild traumatic brain injury (TBI) [primary endpoints]. The investigators will also determine if ALLO improves functional outcome [secondary endpoint]. Participants in this study will receive an intravenous infusion of either ALLO or placebo. Behavioral assessments will be conducted during the infusion and at several time points post-infusion.
Read the detailed description
ALLO is a neurosteroid that exhibits multiple actions highly relevant to the treatment of chronic complex TBI. The investigators' recent human data suggest that ALLO is decreased in patients with TBI, suggesting that ameliorating deficits of this neurosteroid may be clinically therapeutic. In addition, multiple groups have reported ALLO reductions in patients with conditions that frequently co-occur with TBI, including depression and pain disorders. 132 Veterans with a history of mild TBI with co-occurring depression and pain symptoms (chronic complex TBI) will be randomized to either intravenous placebo or ALLO (3 groups/44 participants per group: placebo, lower dose ALLO, higher dose ALLO). Following a loading dose, Veterans will receive placebo or ALLO infusion targeted to achieve serum ALLO levels of 0 nanomolar (nM)(placebo), 50 nM (ALLO lower dose), or 150nM (ALLO higher dose). Behavioral assessments will be conducted during the infusion, post-taper, and 24 hours post-infusion. In addition, the investigators will conduct behavioral assessments 7 days and 14 days post-infusion.
The investigators hypothesize that ALLO will be well-tolerated in patients with complex TBI, and that this intervention may reduce depression and pain symptoms (in addition to potentially improving function).
- Conditions
- Traumatic Brain Injury (TBI)
- Being tested
- Placebo, Allopregnanolone
- Keywords
- Brain Injuries, Traumatic, Depression, Pain
- Medical subject headings
- Brain Injuries, Traumatic, Depression, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
ALLO 0 nanomolar (nM) (placebo: loading dose, 4-hour infusion, taper)
AllopregnanoloneDrug
ALLO 50 nanomolar (nM) (lower dose ALLO: loading dose, 4 hour infusion, taper)
AllopregnanoloneDrug
ALLO 150 nanomolar (nM) (higher dose ALLO: loading dose, 4 hour infusion, taper)
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Experimental | ALLO 0 nanomolar (nM) (placebo: loading dose, 4-hour infusion, taper) Receives: Drug: Placebo |
| ALLO 50 nanomolar (nM) | Experimental | ALLO 50 nanomolar (nM) (lower dose ALLO: loading dose, 4 hour infusion, taper) Receives: Drug: Allopregnanolone |
| ALLO 150 nanomolar (nM) | Experimental | ALLO 150 nanomolar (nM) (higher dose ALLO: loading dose, 4 hour infusion, taper) Receives: Drug: Allopregnanolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brief Pain Inventory, Short Form (BPI-SF) Change
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.
Measured: 6 hours, 24 hours, 7 days, and 14 days
Hamilton-Depression Inventory (HAM-D) Change
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: 6 hours, 24 hours, 7 days, and 14 days
Secondary outcomes (1)
Short Form Health Survey (SF-36) Change
The SF-36 is a health survey with an 8-scale profile embedded in 36 questions that measures physical and mental components of health. Each item is scored on a 0 to 100 range with the lowest and highest possible scores are set at 0 and 100, respectively. All of these items are scored so that a high score defines a more favorable health state.
Measured: 6 hours, 24 hours, 7 days, and 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2019
- Study start1 Dec 2026 (estimated)
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain Injury (TBI)Studies 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 0 nanomolar (nM) ALLO (placebo), 50 nM ALLO (lower dose ALLO) or 150 nM ALLO (higher dose ALLO).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Christine E. Marx, MD MA, Principal investigator, Durham VA Medical Center, Durham, NC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04003285
- Sponsor's protocol ID
- B2798-I
- Other IDs
- 5I01RX002798-05
- Acronym
- ALLO
- Status last verified
- Oct 2026
- First submitted
- 25 Jun 2019
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No