N-acetylcysteine Plus Naltrexone for the Treatment of Alcohol Dependence

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.

Study Overview

• Status: Completed
• Conditions: Alcoholism
• Intervention / Treatment: Drug: N-acetylcysteine + high-dose naltrexone (150 mg); Drug: High-dose naltrexone (150 mg) alone; Drug: Low-dose naltrexone (50 mg) alone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA Connecticut Healthcare System West Haven Campus, West Haven, CT
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Health Care System, Minneapolis, MN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Gihyun Yoon, MD, VA Connecticut Healthcare System West Haven Campus, West Haven, CT

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2010
• Primary Completion (Actual): September 30, 2015
• Study Completion (Actual): October 30, 2016

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: September 30, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Actual): April 8, 2020
• Last Update Submitted That Met QC Criteria: March 31, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: N-acetylcysteine; naltrexone
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Sensory System Agents; Protective Agents; Narcotic Antagonists; Respiratory System Agents; Alcohol Deterrents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Naltrexone; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: CDA-2-014-09F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No