NCT04003285

Allopregnanolone in Chronic Complex Traumatic Brain Injury

Novel Regenerative Therapeutic in Chronic Complex TBI

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 132 (estimated)
• Sponsor: VA Office of Research and Development · Federal
• Sex: All
• Age: 21 Years – 62 Years
• Healthy volunteers: Not accepted

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.

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 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)

Interventions

Type	Name	Description
DRUG	Placebo	ALLO 0 nM (placebo: loading dose, 4-hour infusion, taper)
DRUG	Allopregnanolone	ALLO 50 nM (lower dose ALLO: loading dose, 4 hour infusion, taper)
DRUG	Allopregnanolone	ALLO 150 nM (higher dose ALLO: loading dose, 4 hour infusion, taper)

Timeline

• Start date: 2026-06-01
• Primary completion: 2027-06-01
• Completion: 2027-06-01
• First posted: 2019-07-01
• Last updated: 2026-03-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study