Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers

Study Overview
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Brief Summary
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The purpose of this research study is to find out about the effects of a drug called mavoglurant on alcohol consumption.

Detailed Description
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This project will use a double-blind, placebo-controlled, parallel group design to examine the effects of Mavoglurant on drinking and other alcohol-related behavioral measures in heavy drinkers with Alcohol Use Disorder. Non-treatment-seeking heavy drinkers will participate in three Alcohol Drinking Paradigm (ADP) lab sessions, occurring prior to medication and after the first and second weeks of medication/placebo treatment. They will also participate in two follow-up appointments at one week and one month after participation. The baseline ADP will be used to familiarize subjects with the laboratory procedures and reduce order effects in the subsequent ADP sessions. Subjects will have two 6-day medication outpatient treatment periods (up to 8 days). One group of subjects will receive 100mg of Mavoglurant during the first medication period then 200mg/day of Mavoglurant during the second period. The other group will receive a matching placebo during both medication periods.

Official Title
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Influence of Mavoglurant on Alcohol Craving and Drinking in Heavy Drinkers

Conditions
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Alcohol Consumption, Heavy Drinker, Alcohol Use Disorder (AUD)

Intervention / Treatment
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* Drug: Mavoglurant
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 21-50 (The lower limit is to avoid offering alcohol to individuals below the drinking age of 21. The upper age is determined by experience recruiting for our prior studies). Ability to read English at 6th grade level or higher. Meet DSM-V criteria for moderate or severe AUD . Average weekly alcohol consumption of 30-70 standard drinks for men and 20-65 drinks for women. The lower limits are consistent with the lower sex-specific cut-offs defining high-risk drinking based on World Health Organization Risk Levels (WHO, 2000); the upper limits are designed to avoid recruiting participants whose drinking is likely to exceed the number of drinks available in the ADP. Exclusion Criteria: Individuals who are seeking alcohol treatment or have been in alcohol treatment within the past 6 months. Meet current DSM-V criteria for substance use disorder, except for tobacco use disorder or mild cannabis use disorder. Positive urine drug screens at more than 1 baseline appointment for opiates, cocaine, benzodiazepines and barbiturates. Psychotic or other severe psychiatric disorders as determined by clinical evaluation (SCID). Note that if a subject endorses any harm/risk behaviors (e.g. suicidal/homicidal risk) a licensed clinician will be consulted immediately. Regular use of psychoactive drugs, except for individuals on a stable dose of an antidepressant for at least 2 months. Medical conditions that would contraindicate the consumption of alcohol or use of mavoglurant. Clinically significant abnormalities in screening laboratories, including aspartate aminotransferase (AST) >1.5 times ULN; alanine aminotransferase (ALT) > 1.5 times ULN; total bilirubin >1.5 times ULN; serum creatinine >2.0 times ULN. Neurological trauma or disease, delirium or hallucinations, or clinically significant or unstable medical conditions, including uncontrolled hypertension or diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic diseases, which in the opinion of the study physician and PI, may put the patient at risk because of participation in the study. CIWA-Ar scores of 8 or greater or a history of significant repeated alcohol withdrawals to reduce the likelihood of withdrawal symptomatology if subjects reduce their drinking. Women who are pregnant or nursing. Participants who refuse to use a reliable method of birth control. Subjects who report disliking spirits will be excluded because hard liquor will be provided during the ADP. Subjects who have taken any investigational drug within 4 weeks of the anticipated date of the first study dose. Individuals who report heavy drinking days in the 2 days prior to their intake appointment but have a negative ethyl glucuronide (EtG) test to rule out subjects who are misrepresenting their drinking history. Subjects who have donated blood within the past 6 weeks.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mavoglurant<br>Participants randomized to the Mavoglurant arm will take 100mg of Mavoglurant each day during the first medication period for 6-8 days. During the second medication period, participants will take 200mg of Mavoglurant each day for 6-8 days. | Drug: Mavoglurant<br>* Participants randomized to the Mavoglurant arm will take 100mg of Mavoglurant each day during the first medication period for 6-8 days. During the second medication period, participants will take 200mg of Mavoglurant each day for 6-8 days.<br>|
| Placebo Comparator: Placebo<br>Participants randomized to the placebo arm will take matching placebo tablets during both the first and second medication period. | Other: Placebo<br>* Participants randomized to the placebo arm will take matching placebo tablets during both the first and second medication period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the number of drinks consumed | The number of drinks consumed during the adlib session will be recorded | Baseline, day 6, and day 12 | 
| Change in craving for alcohol | The Cue Exposure Paradigm (CEP) is used to measure craving for alcohol. The task uses a questionnaire that is in the form of a Visual Analog Scale (VAS). The endpoints will be marked with a 0 on the left indicating no craving and a 20 on the right indicating severe craving. Participants will indicate how strong they are craving to drink alcohol. The VAS takes 2-3 minutes to complete. | Baseline, day 6, and day 12 |