A Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder

Study Overview
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Brief Summary
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To explore the effectiveness of n-acetylcysteine in improving treatment outcomes for alcohol use disorder in a double-blind randomised placebo-controlled trial.

Detailed Description
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Australia urgently requires new treatment strategies for the treatment of alcohol dependence. Although alcohol use disorders are a leading cause of preventable death in Australia, their treatment is generally not evidence based. The medications currently approved for use in Australia for the management of alcohol dependence have limited efficacy, and existing research does not address the heterogeneity of treatment response. Targeted personalised medicine addresses this heterogeneity with better medicine selection for patients based on their genotype and clinical comorbidities. Following on from a recent pilot study conducted by CI Morley (NCT03879759), this project will evaluate the clinical efficacy and tolerability of NAC, relative to a placebo, in heavy drinkers. We hypothesise that NAC-treated participants will be better able to achieve a reduction in heavy drinking. We will utilise a double-blind, randomised, controlled design. A sample of 280 individuals will receive 12 weeks of treatment with NAC (2400 mg/day) or placebo.

Official Title
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A Randomised Controlled Trial of N-acetylcysteine for the Management of Alcohol Use Disorder

Conditions
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Alcohol Use Disorder (AUD)

Intervention / Treatment
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* Drug: N-acetyl cysteine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Alcohol Use Disorder according to the DSM-V criteria A desire to reduce or stop drinking Consumed at least 21 standard drinks per week or 2 heavy drinking days per week (HDD: ≥ 5 standard drinks/day for men; ≥4 for women) in the month prior to screening Adequate cognition and English language skills to give valid consent and complete research interviews Stable housing Willingness to give written informed consent Exclusion Criteria: Pregnancy or lactation (women will be advised to use reliable contraception during the trial and a pregnancy test will be performed were necessary) Concurrent use of any psychotropic medication other than antidepressants (provided these are taken at stable doses for at least two months) Any substance dependence other than nicotine Clinically unstable systemic medical (e.g. cancer, end stage liver disease: e.g. MELD score ≥ 10) or psychiatric disorder (e.g. active psychosis, borderline personality disorder, active suicide risk: e.g. MADRAS item 10 score of 6) that precludes trial participation Concurrent use of selenium, vitamin D or other anti-oxidants Any alcohol pharmacotherapy within the past month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: N-acetyl Cysteine<br>Generic name: N-acetyl cysteine. Brand: ACC-600 (Acetylcysteine). Strength: 600mg per capsule. Form: capsule Route: oral Frequency: 2x capsules twice per day = total 4 capsules/day Duration: 12 weeks + Standard of Care: Medical Management. | Drug: N-acetyl cysteine<br>* 2400mg/day<br>* Other names: NAC;|
| Placebo Comparator: Placebo<br>Matched placebo Generic name: dicalcium phosphate Strength: 600mg per capsule Form: capsule Route: oral Frequency: 2x capsules twice per day = total 4 capsules/day Duration: 12 weeks. + Standard of Care: Medical Management. | Drug: Placebo<br>* Matched placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heavy Drinking Days | Reduction in Heavy Drinking Days (HDD; defined as 4 or more drinks in a day for women and five or more drinks in a day for men). This will be measured by the Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Liver Function | Liver Function will be assessed through blood sample at baseline. We will measurement levels of enzyme gamma-glutamyl transferase (GGT), aspartate transaminase (AST), and alanine transaminase (ALT). | 24 weeks | 
| Absence of any HDD | Measured by Timeline Follow Back and corroborated with Phosphatidylethanol (PEth) levels | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-acetyl Cysteine, NAC, Alcohol Dependence, N-acetylcysteine