A Study of NAC for AUD

Study Overview
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Brief Summary
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This proposed pilot study aims to assess the effects of N-acetylcysteine (NAC) on alcohol use disorder (AUD). Despite promising preliminary research, no investigations to date have focused on NAC with alcohol use as the primary aim or on individuals specifically seeking treatment for AUD. The present proposal is an 7-week randomized, double-blind, placebo-controlled study of 3000mg of NAC in up to 50 participants (25 NAC, 25 placebo). The primary aim of the current study is to establish feasibility, dropout rate, and estimate the standard deviation of the outcome measures in order to estimate the required sample for a fully powered clinical trial and to refine the final measures for use in the fully powered clinical trial. Additionally, this study will explore preliminary efficacy signal of NAC.

Detailed Description
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Alcohol abuse is responsible for 1 in 10 deaths among working age adults in the U.S. and costs  $249 billion annually. Currently approved medications for alcohol use disorder (AUD) exert only small to medium effects on drinking, with estimates indicating 12 to 20 drinkers need to be treated for one of them to benefit from the two leading medications, acamprosate and naltrexone. Thus, many patients do not benefit from current pharmacotherapies for AUD. N-acetylcysteine (NAC) is one promising pharmacotherapy that is well-tolerated, safe, and exhibits preliminary evidence across a number of psychiatric and neurological disorders. NAC is available over the counter, has been used all over the world for a variety of conditions, most notably for its 1985 FDA approved use as an antidote for acetaminophen overdose. The NAC dosage was selected as most prior studies in addiction have used 2400-3000mg and even studies up to 3600mg have found it was well-tolerated. Many studies using doses in this range achieved clinically significant improvements, including a study of NAC for smoking cessation which used 3000mg. 7 weeks was selected rather than 12 weeks or longer duration because this within the range of prior clinical trials of NAC (most are 8-12 weeks) and is fitting for the goals of this pilot trial seeking to establish feasibility and sample size for a larger clinical trial. It is beyond the primary aims of this study and the resources of the team to seek longer term outcomes (e.g., drinking at 6 months; https://www.fda.gov/media/91222/download).

Official Title
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A Pilot Study of N-acetylcysteine for Alcohol Use Disorder

Conditions
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Alcohol Use Disorder

Intervention / Treatment
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* Drug: N-acetylcysteine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Greater than or equal to 18 years of age Meets DSM-V criteria for alcohol use disorder on the SCID-5 MHS Healthcare Beneficiary NOTE. While we are recruiting explicitly from the Addiction Treatment Services (ATS) patient population, we do not require that they are currently receiving treatment at ATS. For participants that are not currently in care we will provide them with resources to pursue psychotherapy while engaged in our study as outlined in the interview treatment questions and physical and mental health resource document. Exclusion criteria: Lifetime clinical diagnosis of schizophrenia or bipolar disorder Currently receiving medication for the treatment of alcohol use disorder including oral or injectable naltrexone (ReVia, Vivitrol), disulfiram (Antabuse), and acamprosate (Campral). Pregnancy Lack of English fluency sufficient to complete study measures. Trying to get pregnant in the next 4 months. Hospitalized because of alcohol use in the past 12 months. History of seizures or delirium tremens. History of liver disease Diagnosis of a neurocognitive disorder (e.g., dementia, alzheimer's, mental retardation). Individuals who were never enrolled into Addiction Treatment Services

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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
Interventional Model Description: Arm 1: n-acetylcysteine. 25 participants randomly selected Arm 2: placebo. 25 participants randomly selected
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetylcysteine<br>25 participants randomly selected to receive 1500 milligrams of oral n-acetylcysteine twice daily for 7 weeks. | Drug: N-acetylcysteine<br>* N-acetylcysteine is an FDA approved medication that is used to treat acetaminophen overdose.<br>|
| Placebo Comparator: Placebo<br>25 participants randomly selected to receive placebo twice daily for 7 weeks. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total drinking days | Change in total drinking days will be assessed with the Timeline Follow Back alcohol use assessment | 7 weeks | 
| Change in drinks per drinking day | Change in drinks per drinking day will be assessed with the Timeline Follow Back alcohol use assessment | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in alcohol cue-reactivity | Change in alcohol cue-reactivity will be assessed with a task in which participants are exposed to stimuli associated with alcohol | 7 weeks | 
| Change in alcohol demand | Change in alcohol demand will be assessed with the alcohol purchase task | 7 weeks | 
| Change in alcohol craving | Change in alcohol craving will be assessed with the Penn Alcohol Craving Scale, a 5-item measure of craving for alcohol over the past week. Scores range from 0 to 30, higher scores indicate more alcohol craving. | 7 weeks |