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

Sponsor

Ohio State University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05656534

Collaborator

(none)

Enrollment

Location

Arms

24.1

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: Suvorexant Other: Placebo	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Nov 29, 2022

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control Individuals will take a placebo pill during the Acute Drug Challenge and daily for 28 days.	Other: 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.
Experimental: Suvorexant Treatment Individuals will take 10mg of suvorexant (Merck & Co Inc.) during the Acute Drug Challenge and daily for 28 days.	Drug: 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. Other Names: Belsomra

Arm

Intervention/Treatment

Placebo Comparator: Control

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

Other: 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.

Experimental: Suvorexant Treatment

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

Drug: 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.

Other Names:

Belsomra

Outcome Measures

Primary Outcome Measures

Startle reactivity to stress with an acute dose of suvorexant. [Change from baseline to 2 hours post-ingestion of an acute dose of suvorexant.]
Changes in acoustic startle electromyographic (EMG) response during stress anticipation following an acute dose of suvorexant.
Startle reactivity to stress with daily use of suvorexant. [Change from baseline to post-treatment, up to 1.5-2 months.]
Changes in acoustic startle electromyographic (EMG) response during stress anticipation following daily use of suvorexant.
Alcohol behavior and daily use of suvorexant. [Change from baseline to post-treatment, up to 1.5-2 months.]
Changes in proportion of heavy drinking days and drinks per drinking day following daily use of suvorexant.

Secondary Outcome Measures

Brain change and daily use of suvorexant. [Change from baseline to post-treatment, up to 1.5-2 months.]
Changes in the anterior insula (aINS) and dorsal anterior cingulate cortex (dACC) reactivity and connectivity during stress anticipation following daily use of suvorexant.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.