Alcoholism
Conditions
Keywords
N-acetylcysteine, naltrexone
Brief summary
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
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.
Interventions
DRUGN-acetylcysteine + high-dose naltrexone (150 mg)
All subjects will be evaluated weekly for 12 weeks.
DRUGHigh-dose naltrexone (150 mg) alone
All subjects will be evaluated weekly for 12 weeks.
DRUGLow-dose naltrexone (50 mg) alone
All subjects will be evaluated weekly for 12 weeks.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Heavy Drinking Days | week 1 and week 13 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Penn Alcohol Craving Scale (PACS) | week 1 and week 13 | 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). |
| Obsessive Compulsive Drinking Scale (OCDS) | week 1 and week 13 | 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). |
| Clinical Global Impression (CGI) | week 1 and week 13 | 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). |
| Liver Function Tests (AST) | week 0 and week 13 | — |
| Percentage of Drinking Days | week 1 and week 13 | 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). |
| Drinks Per Drinking Days | week 1 and week 13 | — |
| Liver Function Tests (ALT) | week 0 and week 13 | — |
| Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | week 1 and week 13 | 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). |
Countries
United States
Participant flow
Recruitment details
A total of 111 subjects signed consent. Of 111 subjects, 95 subjects were qualified for the trial.
Participants by arm
| Arm | Count |
|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) N-acetylcysteine + high-dose naltrexone (150 mg): All subjects will be evaluated weekly for 12 weeks. | 31 |
| High-dose Naltrexone (150 mg) Alone High-dose naltrexone (150 mg) alone: All subjects will be evaluated weekly for 12 weeks. | 33 |
| Low-dose Naltrexone (50 mg) Alone Low-dose naltrexone (50 mg) alone: All subjects will be evaluated weekly for 12 weeks. | 31 |
| Total | 95 |
Baseline characteristics
| Characteristic | N-acetylcysteine + High-dose Naltrexone (150 mg) | High-dose Naltrexone (150 mg) Alone | Low-dose Naltrexone (50 mg) Alone | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 33 Participants | 31 Participants | 95 Participants |
| Region of Enrollment United States | 31 Participants | 33 Participants | 31 Participants | 95 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 2 Participants | 9 Participants |
| Sex: Female, Male Male | 29 Participants | 28 Participants | 29 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 31 | 12 / 33 | 9 / 31 |
| serious Total, serious adverse events | 0 / 31 | 0 / 33 | 0 / 31 |
Outcome results
Primary
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).
Time frame: week 1 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Percentage of Heavy Drinking Days | Percentage of heavy drinking days at week 1 | 45.0 percentage of heavy drinking days | Standard Error 4.5 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Percentage of Heavy Drinking Days | Percentage of heavy drinking days at week 13 | 5.2 percentage of heavy drinking days | Standard Error 5.6 |
| High-dose Naltrexone (150 mg) Alone | Percentage of Heavy Drinking Days | Percentage of heavy drinking days at week 1 | 50.6 percentage of heavy drinking days | Standard Error 4.3 |
| High-dose Naltrexone (150 mg) Alone | Percentage of Heavy Drinking Days | Percentage of heavy drinking days at week 13 | 3.4 percentage of heavy drinking days | Standard Error 5.1 |
| Low-dose Naltrexone (50 mg) Alone | Percentage of Heavy Drinking Days | Percentage of heavy drinking days at week 1 | 44.0 percentage of heavy drinking days | Standard Error 4.5 |
| Low-dose Naltrexone (50 mg) Alone | Percentage of Heavy Drinking Days | Percentage of heavy drinking days at week 13 | 3.3 percentage of heavy drinking days | Standard Error 5.3 |
Secondary
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).
Time frame: week 1 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Clinical Global Impression (CGI) | Clinical Global Impression at week 1 | 3.7 units on a scale | Standard Error 0.1 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Clinical Global Impression (CGI) | Clinical Global Impression at week 13 | 1.5 units on a scale | Standard Error 0.2 |
| High-dose Naltrexone (150 mg) Alone | Clinical Global Impression (CGI) | Clinical Global Impression at week 1 | 3.7 units on a scale | Standard Error 0.1 |
| High-dose Naltrexone (150 mg) Alone | Clinical Global Impression (CGI) | Clinical Global Impression at week 13 | 1.7 units on a scale | Standard Error 0.2 |
| Low-dose Naltrexone (50 mg) Alone | Clinical Global Impression (CGI) | Clinical Global Impression at week 1 | 3.6 units on a scale | Standard Error 0.1 |
| Low-dose Naltrexone (50 mg) Alone | Clinical Global Impression (CGI) | Clinical Global Impression at week 13 | 1.4 units on a scale | Standard Error 0.2 |
Secondary
Drinks Per Drinking Days
Time frame: week 1 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Drinks Per Drinking Days | drinks per drinking days at week 1 | 7.3 drinks/drinking day | Standard Error 0.6 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Drinks Per Drinking Days | drinks per drinking days at week 13 | 1.1 drinks/drinking day | Standard Error 0.6 |
| High-dose Naltrexone (150 mg) Alone | Drinks Per Drinking Days | drinks per drinking days at week 1 | 5.9 drinks/drinking day | Standard Error 0.6 |
| High-dose Naltrexone (150 mg) Alone | Drinks Per Drinking Days | drinks per drinking days at week 13 | 1.2 drinks/drinking day | Standard Error 0.6 |
| Low-dose Naltrexone (50 mg) Alone | Drinks Per Drinking Days | drinks per drinking days at week 1 | 7.3 drinks/drinking day | Standard Error 0.6 |
| Low-dose Naltrexone (50 mg) Alone | Drinks Per Drinking Days | drinks per drinking days at week 13 | 1.0 drinks/drinking day | Standard Error 0.6 |
Secondary
Liver Function Tests (ALT)
Time frame: week 0 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Liver Function Tests (ALT) | Liver Function Tests (ALT) at week 13 | 27.6 units/liter | Standard Error 13.9 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Liver Function Tests (ALT) | Liver Function Tests (ALT) at week 0 | 49.4 units/liter | Standard Error 12 |
| High-dose Naltrexone (150 mg) Alone | Liver Function Tests (ALT) | Liver Function Tests (ALT) at week 0 | 36.5 units/liter | Standard Error 11.6 |
| High-dose Naltrexone (150 mg) Alone | Liver Function Tests (ALT) | Liver Function Tests (ALT) at week 13 | 40.1 units/liter | Standard Error 13 |
| Low-dose Naltrexone (50 mg) Alone | Liver Function Tests (ALT) | Liver Function Tests (ALT) at week 0 | 34.7 units/liter | Standard Error 12 |
| Low-dose Naltrexone (50 mg) Alone | Liver Function Tests (ALT) | Liver Function Tests (ALT) at week 13 | 31.3 units/liter | Standard Error 13.2 |
Secondary
Liver Function Tests (AST)
Time frame: week 0 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Liver Function Tests (AST) | Liver function tests (AST) at week 0 | 34.7 units/liter | Standard Error 6.6 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Liver Function Tests (AST) | Liver function tests (AST) at week 13 | 27.3 units/liter | Standard Error 7.9 |
| High-dose Naltrexone (150 mg) Alone | Liver Function Tests (AST) | Liver function tests (AST) at week 0 | 29.0 units/liter | Standard Error 6.4 |
| High-dose Naltrexone (150 mg) Alone | Liver Function Tests (AST) | Liver function tests (AST) at week 13 | 32.1 units/liter | Standard Error 7.4 |
| Low-dose Naltrexone (50 mg) Alone | Liver Function Tests (AST) | Liver function tests (AST) at week 0 | 30.0 units/liter | Standard Error 6.6 |
| Low-dose Naltrexone (50 mg) Alone | Liver Function Tests (AST) | Liver function tests (AST) at week 13 | 22.2 units/liter | Standard Error 7.5 |
Secondary
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).
Time frame: week 1 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Obsessive Compulsive Drinking Scale (OCDS) | Obsessive Compulsive Drinking Scale at week 1 | 28.2 units on a scale | Standard Error 1.8 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Obsessive Compulsive Drinking Scale (OCDS) | Obsessive Compulsive Drinking Scale at week 13 | 9.1 units on a scale | Standard Error 2.1 |
| High-dose Naltrexone (150 mg) Alone | Obsessive Compulsive Drinking Scale (OCDS) | Obsessive Compulsive Drinking Scale at week 1 | 29.0 units on a scale | Standard Error 1.7 |
| High-dose Naltrexone (150 mg) Alone | Obsessive Compulsive Drinking Scale (OCDS) | Obsessive Compulsive Drinking Scale at week 13 | 14.0 units on a scale | Standard Error 1.9 |
| Low-dose Naltrexone (50 mg) Alone | Obsessive Compulsive Drinking Scale (OCDS) | Obsessive Compulsive Drinking Scale at week 1 | 24.5 units on a scale | Standard Error 1.8 |
| Low-dose Naltrexone (50 mg) Alone | Obsessive Compulsive Drinking Scale (OCDS) | Obsessive Compulsive Drinking Scale at week 13 | 9.0 units on a scale | Standard Error 2 |
Secondary
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).
Time frame: week 1 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Penn Alcohol Craving Scale (PACS) | Penn Alcohol Craving Scale at week 1 | 18.0 units on a scale | Standard Error 1.1 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Penn Alcohol Craving Scale (PACS) | Penn Alcohol Craving Scale at week 13 | 7.2 units on a scale | Standard Error 1.4 |
| High-dose Naltrexone (150 mg) Alone | Penn Alcohol Craving Scale (PACS) | Penn Alcohol Craving Scale at week 1 | 18.4 units on a scale | Standard Error 1.1 |
| High-dose Naltrexone (150 mg) Alone | Penn Alcohol Craving Scale (PACS) | Penn Alcohol Craving Scale at week 13 | 8.3 units on a scale | Standard Error 1.3 |
| Low-dose Naltrexone (50 mg) Alone | Penn Alcohol Craving Scale (PACS) | Penn Alcohol Craving Scale at week 1 | 16.1 units on a scale | Standard Error 1.1 |
| Low-dose Naltrexone (50 mg) Alone | Penn Alcohol Craving Scale (PACS) | Penn Alcohol Craving Scale at week 13 | 6.3 units on a scale | Standard Error 1.3 |
Secondary
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).
Time frame: week 1 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Percentage of Drinking Days | percentage of drinking days at week 1 | 64.6 percentage of drinking days | Standard Error 6.3 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Percentage of Drinking Days | percentage of drinking days at week 13 | 21.1 percentage of drinking days | Standard Error 7.6 |
| High-dose Naltrexone (150 mg) Alone | Percentage of Drinking Days | percentage of drinking days at week 1 | 63.8 percentage of drinking days | Standard Error 6.1 |
| High-dose Naltrexone (150 mg) Alone | Percentage of Drinking Days | percentage of drinking days at week 13 | 24.5 percentage of drinking days | Standard Error 7 |
| Low-dose Naltrexone (50 mg) Alone | Percentage of Drinking Days | percentage of drinking days at week 1 | 55.3 percentage of drinking days | Standard Error 6.3 |
| Low-dose Naltrexone (50 mg) Alone | Percentage of Drinking Days | percentage of drinking days at week 13 | 18.2 percentage of drinking days | Standard Error 7.3 |
Secondary
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).
Time frame: week 1 and week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Q-LES-Q at week 1 | 53.2 units on a scale | Standard Error 1.9 |
| N-acetylcysteine + High-dose Naltrexone (150 mg) | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Q-LES-Q at week 13 | 61.6 units on a scale | Standard Error 2.1 |
| High-dose Naltrexone (150 mg) Alone | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Q-LES-Q at week 13 | 59.6 units on a scale | Standard Error 2 |
| High-dose Naltrexone (150 mg) Alone | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Q-LES-Q at week 1 | 53.8 units on a scale | Standard Error 1.8 |
| Low-dose Naltrexone (50 mg) Alone | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Q-LES-Q at week 1 | 55.1 units on a scale | Standard Error 1.9 |
| Low-dose Naltrexone (50 mg) Alone | Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) | Q-LES-Q at week 13 | 63.9 units on a scale | Standard Error 2.1 |