Medication Development in Alcoholism: Suvorexant Versus Placebo

Study Overview
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Brief Summary
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The primary hypotheses under test are that alcohol dependent subjects treated with suvorexant will report decreased craving for alcohol following alcohol exposure in the laboratory and report significantly less drinking under naturalistic conditions, than those treated with placebo. Suvorexant (Belsomra®) received approval by the FDA in 2014 for treatment of insomnia. To control for any effect of pre-existing sleep disturbance for which suvorexant may be indicated, subjects will be stratified on the basis of a Pittsburgh Sleep Quality Index total score of > 5 versus <5. Subjects were also stratified by sex.

Official Title
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Medication Development for Protracted Abstinence in Alcoholism: Suvorexant Versus Placebo

Conditions
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Alcohol Use Disorder (AUD)

Intervention / Treatment
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* Drug: Suvorexant 20 mg
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female volunteers, 18-65 years of age. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for current alcohol use disorder of moderate or greater severity (AUD-MS). In the month prior to screening, reports drinking ≥ 21 standard drinks per week if male, ≥ 14 if female, with at least one heavy drinking day (≥ 5 males, ≥ 4 females) per week. Subjects will not be seeking treatment because the medication studies are not treatment trials, and to avoid exposing treatment-seekers to alcohol cues Subjects must be abstinent a minimum of 3 days (but not more than 7 days) prior to the human lab session. Negative blood alcohol content (BAC) and a Clinical Institute Withdrawal Assessment (CIWA) score of < 9 at time of randomization and lab session to eliminate acute alcohol or withdrawal effects on dependent measures. In acceptable health in the judgment of the study physician, on the basis of interview, medical history, physical exam, EKG, routine urine and blood chemistry. Subjects with a history of depression, who have been on a stable dose of anti-depressant medication for at least 3 months, and do not meet current DSM-5 criteria for depression or anxiety. Females with childbearing potential must have a negative pregnancy test on the screening and randomization visits and agree to use effective birth control for the duration required by a given study. Able to provide informed consent and understand questionnaires and study procedures in English. Willing to comply with the provisions of the protocol and take oral medication. Exclusion Criteria: Meets DSM-5 criteria for a major psychiatric disorder, including mood or anxiety disorders or substance use disorders other than alcohol or nicotine, or, mild cannabis use disorder Has a urine drug screen (UDS) positive for substances of abuse other than alcohol or marijuana Significant medical disorders that will increase potential risk or interfere with study participation as determined by the study physician. Liver function tests more than 3 times the upper limit of normal or elevated bilirubin. Subjects taking digoxin or CYP3A inhibitors or inducers, metabolism by CYP3A is the major elimination pathway for suvorexant. Treatment within the month prior to screening with (1) an investigational drug, (2) medications which may negatively interact with study medications, or (3) drugs that may influence study outcomes (e.g., disulfiram [Antabuse], naltrexone [ReVia], acamprosate [Campral], or anticonvulsants). Ongoing treatment with medications that may increase risk, including prescribed, over-the-counter, and herbal preparations, as determined by the study physician. Sexually active female subjects with childbearing potential who are pregnant, nursing, or refuse to use effective methods of birth control for the duration of the study. No fixed domicile and/or no availability by home or mobile telephone. History of hypersensitivity to the study drug or the ingredients. Failure to take double-blind medication as prescribed.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment, Double-Blind, Randomized Stratified at randomization based on sex and Pittsburgh Sleep Quality Index Total Score (PSQI) greater than or equal to 5 versus less than 5.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Belsomra,(suvorexant)<br>20 mg single-dose administration given on an inpatient clinical research unit | Drug: Suvorexant 20 mg<br>* Single-dose administration of 20 mg suvorexant given on an inpatient clinical research unit<br>* Other names: Belsomra;|
| Placebo Comparator: Placebo<br>Placebo single-dose administration given on an inpatient clinical research unit | Drug: Placebo oral tablet<br>* Single-dose administration of placebo given on an inpatient clinical research unit<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Scale (VAS) of Craving Severity: 2 Arms | VAS to alcohol cues minus VAS to water cues on a 0-20 VAS scale. Higher scores indicate greater craving strength with a minimum score of 0 and a maximum score of 20. | 1 hour during cue reactivity session | 
| Visual Analog Scale (VAS) Strength of Craving: Combined Arms Conditional Model | VAS to alcohol cues minus VAS to water cues on a 0-20 VAS scale. Higher scores indicate greater craving strength with a minimum score of 0 and a maximum score of 20. | 1 hour during cue reactivity session | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Standard Drinks Per Day: 2 Arms | Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcohol drinks consumed per day with a minimum value of 0 and an undetermined maximum value | Up to one week following single dose administration | 
| Number of Standard Drinks Per Day: Combined Arms Conditional Model | Number of standard drinks per day using the Timeline Followback Interview (TLFB). Total number of alcoholic drinks consumed per day with a minimum value of 0 and an undetermined maximum value. | Up to one week following single dose administration |