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

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ohio State University
• Treatments: Suvorexant

Criteria

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 30.

• 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.