Protocol Title: Effect of Sublingual formulation of Dexmedetomidine HCl (BXCL501) on Ethanol in Heavy Drinkers with PTSD – Alcohol Interaction Study
Objective:
The overall objective of the proposed study is to determine if Dexmedetomidine HCl (BXCL501) is safe for treatment of alcohol use disorder (AUD) with comorbid posttraumatic stress disorder (PTSD) and also shows potential signals of efficacy thereby supporting the conduct of later phase clinical trials. Safety endpoints will be compared following an alcohol challenge without and concurrent with BXCL501 treatment.
Hypothesis:
Hypothesis 1 (Specific Aim 1):
1a. To evaluate whether pretreatment with BXCL501 40 µg and 80 µg attenuates stress reactivity in individuals with alcohol use disorder and PTSD. Participants will undergo stress (PTSD) reactivity in the laboratory; outcomes will include measures of anxiety, craving for alcohol and other mood disturbances.
1b. To evaluate whether pretreatment with BXCL501 40 µg and 80 µg attenuates cue reactivity in individuals with AUD and PTSD (clinical or subclinical). Participants will undergo alcohol cue induced craving in the laboratory and outcomes will include craving for alcohol, anxiety and other mood disturbances.
Hypothesis 2 (Specific Aim 2):
2a. To evaluate whether pretreatment with BXCL501 40 µg and 80 µg alters subjective effects of ethanol in a laboratory setting. Ethanol will be administered intravenously using “clamp” methodology and the outcomes include stimulant and sedative effects, cognitive function, cerebellar function and reaction time.
2b. To evaluate whether pretreatment with BXCL501 40 µg and 80 µg increases side effect associated with ethanol administration including sedation and vital signs.
Population: n = 10 individuals with AUD and PTSD
Study Synopsis:
This laboratory study is a phase 1, double-blind, placebo-controlled, within subjects study. This study will consist of 3 laboratory test sessions following pretreatment with BXCL501/placebo for 10 heavy drinker participants with comorbid PTSD. Participants (n=10) will participate in a laboratory study with 3 test days (minimum of 2 days, but no longer than 2 weeks between each test session); for each test day they will be assigned to receive sublingual BXCL501 40µg, 80µg and placebo in a randomized fashion. Test sessions will be conducted to evaluate stress (PTSD) reactivity and alcohol cue reactivity. Participants will also receive IV ethanol administered via “clamp methodology” to assess for the effects of BXCL501 in combination with ethanol.