Orexin Receptor Antagonists as Modulators of Threat Sensitivity in Individuals With Alcohol Use Disorder

2022H0265

The goal of this double-blind clinical trial is to further explore if, how, and for whom orexin antagonism modifies brain-behavior stress targets in moderate to severe alcohol use disorder (AUD). The main questions it aims to answer are: * Does an acute dose of suvorexant (SUV) and/or daily use of SUV modify brain-behavior targets of AUD dysfunction? * Does daily SUV use change alcohol behavior and if so, is this change in behavior linked to brain-behavior change? Participants will be randomized to a treatment group (SUV or placebo) and protocol arm, electromyography (EMG) only or EMG+functional magnetic resonance imaging (fMRI). Participants will be asked to complete the following: * Baseline lab visit(s) that include the psychophysiological stress paradigm (EMG only or EMG+fMRI, dependent upon randomization). * Acute drug challenge where the participant will return to the lab to repeat the stress paradigm following administration of a single dose of either 10mg SUV or placebo. * Medication trial where participants will be instructed to take 10mg capsules of SUV or placebo orally each night before bedtime for 4-weeks. * Daily reports of medication adherence, side-effects, sleep, alcohol use, and mood will be collected via smartphones during the 4-week medication trial. * Post-treatment lab visit(s) where participants will return to the lab at the end of the medication trial and complete the same stress paradigm from baseline (EMG only or EMG+fMRI, dependent upon randomization).

2022-11-29

2024-10-31

2024-12-30

Recruiting

Early phase I

80

Inclusion Criteria: * Age 18-65. * Participant is able to give informed consent. * Generally medically and physically healthy as confirmed by medical history. * Meet DSM-5 diagnostic criteria for current moderate or severe AUD. * Engage in heavy alcohol use defined as drinking equal or greater than 14 standard drinks per week if male and equal or greater than 7 standard drinks per week if female. Exclusion Criteria: * Clinically significant medical or neurological condition (e.g., liver disease, narcolepsy, complex sleep behaviors, severe hepatic impairment, COPD, severe obstructive sleep apnea). * Current cognitive dysfunction (traumatic brain injury, mental retardation, organic mental syndrome, pervasive developmental disorder, or dementia). * Current use of antihistamines, strong or moderate inhibitors of CYP3A liver enzymes, strong CYP3A inducers, or digoxin. * Current or past DSM-5 diagnosis of mania, schizophrenia, psychosis, suicidality, major depressive disorder, or obsessive compulsive disorder. * Current substance use disorder other than alcohol or mild cannabis use disorder. * Treatment seeking for AUD. * Recent psychotropic medication use in the past 2 months. * Currently smokes 5 or more cigarettes (or electronic equivalent) per day. * BMI equal or greater than 35. * Engage in night-shift work. * Lack of fluency in English. * Presence of ferrous-containing metal in the body. * Inability to tolerate small, enclosed spaces. * Deafness in one or both ears. * Currently pregnant (positive pregnancy test), lactating, or not agreeing to use birth control methods during the duration of the trial.

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2024-01-11