Acamprosate vs. Placebo in Bipolar Alcoholics

Study Overview
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Brief Summary
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To conduct a double-blind, randomized, placebo-controlled outpatient clinical trial of acamprosate in individuals with alcohol dependence and bipolar disorder who are also receiving mood stabilizing medication. The study will assess the safety and efficacy of acamprosate in alcohol-dependent bipolar patients as measured by its effects on alcohol use and mood symptoms relative to placebo. The primary hypothesis to be tested is whether individuals with comorbid bipolar disorder and alcohol dependence who receive acamprosate plus mood stabilizer will have greater improvement in alcohol-related outcomes than those who receive mood stabilizer alone. A secondary hypothesis that will be explored is that alcohol-dependent bipolar individuals treated with acamprosate will have greater mood stability as compared to those treated with mood stabilizers alone.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Trial of Acamprosate in Alcohol-Dependent Individuals With Comorbid Bipolar Disorder

Conditions
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Alcohol Dependence, Bipolar Disorder

Intervention / Treatment
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* Drug: Acamprosate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults ages 18-65 Meet DSM-IV criteria for current (past 90 days) alcohol dependence Meet DSM-IV criteria for bipolar I or bipolar II disorder Currently on a mood stabilizing medication regimen, including the use of lithium, valproic acid, lamotrigine, carbamazepine, and/or antipsychotic agent FDA approved to treat bipolar disorder without any dosage adjustments in the past 30 days Must be able to remain free from alcohol for at least 3 days prior to medication initiation Subjects must be able to adequately provide informed consent and function at an intellectual level sufficient to allow the accurate completion of all assessment instruments Subjects must consent to random assignment and be willing to commit to medication treatment and follow-up assessments Exclusion Criteria: Individuals with a primary psychiatric disorder other than bipolar disorder Individuals with an uncontrolled neurologic condition that could confound the results of the study Individuals with an uncontrolled medical condition that may adversely affect the conduct of this trial or jeopardize the subject's safety Participants with creatinine clearance less than or equal to half of normal value as indicated by chem. 7 results conducted at screening visit. Concomitant use of other psychotropic medications not allowed per the protocol Women of childbearing potential who are pregnant, lactating or refuse to use adequate forms of birth control Current suicidal or homicidal risk Baseline scores of > 35 on the Montgomery Asberg Depression Rating Scale and/or > 25 on the Young Mania Rating Scale

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acamprosate<br>666 mg p.o. TID | Drug: Acamprosate<br>* 666 mg po TID<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* 2 tabs po TID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Drink (Days) | Number of days after randomization until consumption of first alcoholic beverage per self-report. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Days Abstinent | Percentage of days in trial with no alcohol consumption | 8 weeks | 
| Percent Heavy Drinking Days | Percentage of drinking days that are heavy drinking days (5 or more standard drinks/day for males, 4 or more standard drinks/day for females) | 8 weeks | 
| Percent Carbohydrate-deficient Transferrin | Measured level of validated serum alcohol biomarker | 8 weeks | 
| Gamma-glutamyltransferase | Measured levels of validated serum alcohol biomarker | 8 weeks | 
| Obsessive Compulsive Drinking Scale Score | Higher scores indicate worse outcome; minimum score = 0, maximum score = 40 | 8 weeks | 
| Montgomery Asberg Depression Rating Scale Score | MADRS scores at study endpoint. Higher scores indicate a worse outcome. Minimum score = 0, maximum score = 60. | 8 weeks | 
| Young Mania Rating Scale Score | YMRS scores at study endpoint. Higher scores indicate a worse outcome. Minimum score = 0, maximum score = 60. | 8 weeks | 
| Clinical Global Impression Scale Score | Higher values indicate worse outcomes; minimum value = 1, maximum value = 7 | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acamprosate, Alcoholism, Bipolar disorder, Comorbidity, Craving, Depression, GABA, Glutamate, Mania, Pharmacotherapy, Withdrawal