An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence

Study Overview
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Brief Summary
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The principal aim of this exploratory study is to examine whether the addition of aripiprazole to naltrexone will enhance efficacy over naltrexone alone in a 16-week randomized, placebo-controlled clinical trial, in which all subjects will be provided medical management as delivered in the COMBINE Study (Anton et al, 2006). To test whether medication treatment will reduce drinking compared to placebo treatment alone in the context of medical management and whether naltrexone plus aripiprazole will reduce drinking compared to naltrexone treatment alone in the context of medical management.

Official Title
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An Exploratory Study of Naltrexone Plus Aripiprazole for Alcohol Dependence

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: Placebo
* Drug: Naltrexone
* Drug: Naltrexone + Aripiprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 70 Subjects will meet criteria for primary alcohol dependence operationalized as follows: A. Meets the DSM IV criteria for alcohol dependence including loss of control over drinking (criterion 3) B. Has not had more than one previous inpatient medical detoxification Consumes, on average, at least 10 standard drinks per drinking day for men and 8 drinks per day for women in the 90 days pre-screening (to select an appropriately heavy drinking population) Able to maintain sobriety for four days (with or without the aid of alcohol detoxification medications) as determined by self report, collateral report, and breathalyzer measurements Able to read and understand questionnaires and informed consent Lives within approximately 50 miles of the study site - Exclusion Criteria: Currently meets DSM IV criteria for any other psychoactive substance dependency disorder except nicotine dependence Ever abused opiates Any psychoactive substance abuse, except marijuana and nicotine, within the last 30 days as evidenced by subject report, collateral report, or urine drug screen Meets DSM IV criteria for current axis I disorders of major depression, panic disorder, obsessive compulsive disorder, post traumatic stress syndrome, bipolar affective disorder, schizophrenia, or any other psychotic disorder or organic mental disorder Meets DSM IV current criteria for dissociative disorder or eating disorders Has current suicidal ideation or homicidal ideation Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications Current use of disulfiram Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problem that would impair participation or limit medication ingestion Hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at least 3.0 times normal at screening and/or after 5 days abstinence Sexually active female of child-bearing potential who is pregnant (by urine HCG), nursing, or who is not using a reliable form of birth control Has current charges pending for a violent crime (not including DUI-related offenses) Does not have a stable living situation and a reliable source of collateral reporting Has taken an opiate antagonist drug in the last month Has taken aripiprazole in the last month or has experienced adverse effects from it at any time in the past

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: Placebo<br>* placebo<br>|
| Active Comparator: 2<br>Naltrexone | Drug: Naltrexone<br>* Naltrexone (25mg or 50 mg per titration schedule)<br>|
| Active Comparator: 3<br>Naltrexone + Aripiprazole | Drug: Naltrexone + Aripiprazole<br>* Naltrexone + Aripiprazole (5mg - 15mg per titration schedule)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drinks Per Drinking Day | Standard drinks per drinking day | 16-week treatment period | 
| Percent Heavy Drinking Days | percent of total 112 day trial in which heavy drinking occurred (>=4 for females, >=5 male) | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pill Counts During Treatment | Compliance with medication as determined by pill counts | 16-week | 
| Percent Riboflavin Positive Urine Samples as a Measure of Medication Compliance | Riboflavin was added to each individual capsule of medication and measured as a proxy for compliance with the medication regime | 16 weeks treatment trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alcohol Dependence, Alcoholism, Naltrexone, Aripiprazole, Substance Abuse