Allopregnanolone in Chronic Complex Traumatic Brain Injury

NCT04003285 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: B2798-I
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief 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 \[secondary endpoint\]. 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.

Conditions

Traumatic Brain Injury (TBI)

Keywords

Brain Injuries, Traumatic; Depression; Pain

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  6 hours, 24 hours, 7 days, and 14 days

Secondary Outcomes (1)

• Short Form Health Survey (SF-36) Change

  6 hours, 24 hours, 7 days, and 14 days

Study Arms (3)

Placebo

EXPERIMENTAL

ALLO 0 nM (placebo: loading dose, 4-hour infusion, taper)

Drug: Placebo

ALLO 50 nM

EXPERIMENTAL

ALLO 50 nM (lower dose ALLO: loading dose, 4 hour infusion, taper)

Drug: Allopregnanolone

ALLO 150 nM

EXPERIMENTAL

ALLO 150 nM (higher dose ALLO: loading dose, 4 hour infusion, taper)

Drug: Allopregnanolone

Interventions

Placebo DRUG

ALLO 0 nM (placebo: loading dose, 4-hour infusion, taper)

Placebo

Allopregnanolone DRUG

ALLO 50 nM (lower dose ALLO: loading dose, 4 hour infusion, taper)

ALLO 50 nM

Eligibility Criteria

• Age: 21 Years - 62 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

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)
• 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
• HAM-D score 14 (HAM-D range for moderate depression=14-18)
• Participants will meet DSM-5 criteria for major depressive disorder (by SCID)
• 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

You may not qualify if:

• Participants with current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern
• 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
• 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 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

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705-3875, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Depression; Pain

Interventions

Pregnanolone

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Behavioral Symptoms; Behavior; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Christine E. Marx, MD MA

  Durham VA Medical Center, Durham, NC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine E Marx, MD MA

CONTACT

(919) 286-0411; christine.marx@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a randomized, double-blind, placebo-controlled trial. All roles will be masked with the exception of the research pharmacist
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Participants will be randomized to receive 0 nM ALLO (placebo), 50 nM ALLO (lower dose ALLO) or 150 nM ALLO (higher dose ALLO).

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: July 1, 2019
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)