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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
132
ALLO 0 nanomolar (nM) (placebo: loading dose, 4-hour infusion, taper)
ALLO 50 nanomolar (nM) (lower dose ALLO: loading dose, 4 hour infusion, taper)
ALLO 150 nanomolar (nM) (higher dose ALLO: loading dose, 4 hour infusion, taper)
Durham VA Medical Center, Durham, NC
Durham, North Carolina, United States
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.
Time frame: 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.
Time frame: 6 hours, 24 hours, 7 days, and 14 days
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.
Time frame: 6 hours, 24 hours, 7 days, and 14 days
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