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

NCT ID: NCT05656534

Last Updated: 2025-10-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-29
• Study Completion Date: 2024-08-01

Brief 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).

Conditions

Alcohol Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Control

Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits.

Suvorexant Treatment

Individuals will take 10mg of suvorexant (Merck \& Co Inc.) during the Acute Drug Challenge and daily for 28 days.

Group Type: EXPERIMENTAL

Suvorexant

Intervention Type: DRUG

This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits.

Interventions

Suvorexant

This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). Suvorexant (SUV) will be placed in opaque capsules with dextrose filler. After the pre-treatment visits participants will take one pill of SUV at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete an EMG. Laboratory assessments will occur during peak concentration, 2 hours post-ingestion. At the end of the visit, participants will be given a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side effects and potential drug-drug interactions. At the end of the 28 days, participants will complete post-treatment lab visits.

Intervention Type: DRUG

Placebo

This study is a double-blind study. Participants will complete an initial screening visit and pre-treatment lab visits (EMG, fMRI). The placebo pill will be identical in appearance to suvorexant but will contain only dextrose. Following the pre-treatment visits, participants will take one pill at the Acute Drug Challenge under medical supervision. Ninety minutes post ingestion participants will complete the EMG paradigm. At the end of the visit participants will be provided a blister pack with 28 pills. Participants will be instructed to take one pill orally about 30 minutes prior to sleep time each night for 28 days. Participants will be provided education about common side effects. Participants will complete daily surveys to monitor side. At the end of the 28 days, participants will complete post-treatment lab visits.

Intervention Type: OTHER

Other Intervention Names

Belsomra

Eligibility 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 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: lead

Responsible Party

Stephanie M Gorka, PhD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Ohio State University

Columbus, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R21AA030097-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2022H0265

Identifier Type: -

Identifier Source: org_study_id