The Efficacy and Neurobehavioural Mechanism of N-acetyl Cysteine (NAC) for Alcohol Dependence

Study Overview
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Brief Summary
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The study will explore the efficacy and tolerability of a regimen of NAC (2400 mg) versus placebo for the treatment of alcohol dependence.

Detailed Description
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Study 1: Relapse prevention: This is a double-blind, randomized, placebo-controlled clinical trial in which participants will receive oral NAC (2400 mg: 2x 600mg tablets twice per day) or matching placebo. Trial participants will receive either oral NAC ( dose stated above) or matching placebo for up to 4 weeks. Study 2: Withdrawal: Trial participants will receive oral NAC (dose stated above) or matching placebo within the first 24 hours of their admission for up to 3 days. Study 3: Participants from the relapse prevention substudy will also receive 30-minute non-invasive brain imaging session prior to and after completing the treatment regime in Study 1. Both males and females will be recruited for the study.

Official Title
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The Efficacy and Neurobehavioural Mechanism of N-acetyl Cysteine for Alcohol Dependence: An Exploratory Pilot Study

Conditions
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Alcohol Dependence

Intervention / Treatment
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* Drug: NAC 2400mg/day
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between the ages of 18 and 65 meeting DSM-IV criteria for current alcohol use disorder (this is an exclusion for the healthy control sample) Able to understand and sign written informed consent Must have a stable residence and be able to identify an individual who could locate subject if needed Admitted for medical detoxification from alcohol (withdrawal study only) Blood alcohol concentration of 0.00 (if completing brain imaging session) Express a desire to achieve abstinence or to greatly reduce alcohol consumption (relapse prevention study only) Exclusion Criteria: Clinically significant comorbidities or medical disease that might interfere with the evaluation of the study medication or present a safety concern. Pregnant women and women of childbearing potential who do not practice a medically acceptable form of birth control Women who are breastfeeding Dependence on any substance other than nicotine Court-mandated participation in alcohol treatment or pending incarceration (relapse prevention study only) Treatment/ingestion during the previous week of benzodiazepines or other sedative-hypnotic medications or history of recent chronic treatment with sedative-hypnotic medications (withdrawal study only) Dependence on any substance other than nicotine The following exclusion criteria are only applicable to participants undergoing the brain imaging session: Extreme obesity Pregnant or have any reason to believe they are pregnant; Previous brain surgery; Ever employed as a machinist, a welder or a metal worker; Epilepsy Metal items such as pacemakers; aneurysm clips in the brain; metal dental implants; metallic fragments in the eye or anywhere else; insulin pump; metal implants; hearing aid or a prosthetic device.

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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Accepts Healthy Volunteers

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
Interventional Model Description: Study 1: NAC vs Placebo (PL) (4 weeks outpatient) Study 2: NAC vs PL (3 days inpatient) Study 2: NAC vs PL (neuromaging session before vs after treatment)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>NAC - Relapse Prevention (4 wks) | Drug: NAC 2400mg/day<br>* 2400mg/day 2 x 600mg b.d<br>|
| Placebo Comparator: Arm 2<br>NAC - Relapse Prevention (4 wks) | Drug: Placebo<br>* 4 matched placebo tablets/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study 1: Alcohol consumption | as measured by the number of heavy drinking days per week and number of drinks per drinking day | 4 weeks | 
| Study 1: Alcohol consumption | as measured by the abstinence rate, time to relapse and time to lapse | 4 weeks | 
| Study 2: Amount of Benzodiazepines administered | as measured by the number of benzodiazepines administered in the NAC vs placebo groups | 3 days | 
| Study 2: Amount of Benzodiazepines administered | as measured by Alcohol Withdrawal Scale (AWS) score | 3 days | 
| Study 2: Amount of Benzodiazepines administered | as measured by Visual Analogue Scale (VAS) score | 3 days | 
| Study 2: Amount of Benzodiazepines administered | as measured by Alcohol Urge Questionaire (AUQ) Score | 3 days | 
| Study 3: Markers of neural inflammation and responses to alcohol cue | as measured by differences in cortical levels of glutathione | 4 weeks | 
| Study 3: Markers of neural inflammation and responses to alcohol cue | as measured by differences in cortical levels of N-acetylaspartate | 4 weeks | 
| Study 3: Markers of neural inflammation and responses to alcohol cue | as measured by blood oxygen level dependent (BOLD) brain activation differences to alcohol cues (alcohol cue activation) | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alcohol craving | as measured by Penn Alcohol Craving Scale (PACS) score | 4 weeks | 
| Mood | as measured by Depression Anxiety Stress Scale (DASS) score | 4 weeks |