N-acetylcysteine Plus Naltrexone for the Treatment of Alcohol Dependence

Study Overview
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Brief Summary
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The purpose of this study is to determine whether: (1) the combination of N-acetylcysteine + high-dose naltrexone (150 mg) works better than high-dose naltrexone (150 mg) alone in reducing alcohol drinking; and (2) high-dose naltrexone (150 mg) alone works better than low-dose naltrexone (50 mg) alone in reducing alcohol drinking.

Detailed Description
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The 3 groups (N-acetylcysteine plus naltrexone 150 mg, naltrexone 150 mg, and naltrexone 50 mg) will be compared in a 12-week randomized, double-blind clinical trial.

Official Title
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N-acetylcysteine Plus Naltrexone for the Treatment of Alcohol Dependence

Conditions
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Alcoholism

Intervention / Treatment
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* Drug: N-acetylcysteine + high-dose naltrexone (150 mg)
* Drug: High-dose naltrexone (150 mg) alone
* Drug: Low-dose naltrexone (50 mg) alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-65 years alcohol dependence by DSM-IV criteria heavy drinking at least 6 times within the past month ('heavy drinking' defined as 5 or more standard drinks per day for men and 4 or more standard drinks for women) able to provide informed consent a score of 6 or more on the Penn Alcohol Craving Scale (PACS) subject agrees not to take over-the-counter analgesics during the study Exclusion Criteria: current drug abuse or dependence by DSM-IV criteria (except nicotine and marijuana) current psychotic disorders or bipolar disorders current suicidal or homicidal ideation positive illicit drug screen test (except marijuana) ongoing narcotic use or risks for narcotic use during the study increased risk for severe alcohol withdrawal by a score of 10 or more on the Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) clinically significant cardiac, hepatic, renal, neurologic, or pulmonary disease baseline aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 times normal current use of disulfiram, acamprosate or topiramate pregnant or nursing, or inadequate birth control methods in women of childbearing potential alcohol breathalyzer level 0.08 or more at the screening visit severe alcohol withdrawal (delirium tremens or withdrawal seizures) within the past year currently requiring inpatient treatment for treating alcohol dependence

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>N-acetylcysteine + high-dose naltrexone (150 mg) | Drug: N-acetylcysteine + high-dose naltrexone (150 mg)<br>* All subjects will be evaluated weekly for 12 weeks.<br>|
| Experimental: Arm 2<br>High-dose naltrexone (150 mg) alone | Drug: High-dose naltrexone (150 mg) alone<br>* All subjects will be evaluated weekly for 12 weeks.<br>|
| Active Comparator: Arm 3<br>Low-dose naltrexone (50 mg) alone | Drug: Low-dose naltrexone (50 mg) alone<br>* All subjects will be evaluated weekly for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Heavy Drinking Days | Percentage of heavy drinking days was measured by the Time Line Follow Back (TLFB) Method. ('Heavy drinking' was defined as 5 or more standard drinks per day for men and 4 or more standard drinks for women.) The percentage has a total range of 0%-100%. Higher percentages represent a worse outcome (i.e., more heavy drinking). | week 1 and week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver Function Tests (AST) |  | week 0 and week 13 | 
| Penn Alcohol Craving Scale (PACS) | The Penn Alcohol Craving Scale is designed to assess alcohol craving severity. The scale has a total score range of 0-30. Higher values represent a worse outcome (i.e., higher craving). | week 1 and week 13 | 
| Obsessive Compulsive Drinking Scale (OCDS) | The Obsessive Compulsive Drinking Scale is designed to assess obsessive and compulsive aspects of alcoholism. The scale has a total score range of 0-56. Higher values represent a worse outcome (i.e., more alcohol problems). | week 1 and week 13 | 
| Clinical Global Impression (CGI) | The Clinical Global Impression is designed to assess overall severity of illness. The scale has a total score range of 1-7. Higher values represent a worse outcome (i.e., severe illness). | week 1 and week 13 | 
| Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | The Quality of Life Enjoyment and Satisfaction Questionnaire is designed to assess a quality of life. The scale has a total score range of 16-80. Higher values represent a better outcome (i.e., better quality of life). | week 1 and week 13 | 
| Percentage of Drinking Days | Percentage of drinking days was measured by the Time Line Follow Back (TLFB) Method. The percentage has a total range of 0%-100%. Higher percentages represent a worse outcome (i.e., more drinking days). | week 1 and week 13 | 
| Drinks Per Drinking Days |  | week 1 and week 13 | 
| Liver Function Tests (ALT) |  | week 0 and week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-acetylcysteine, naltrexone