Clinical trial NCT04964843: A Study of NAC for AUD
Official title: A Pilot Study of N-acetylcysteine for Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Alcohol Use Disorder
Lead sponsor: Uniformed Services University of the Health Sciences
Sponsor class: FED
First posted: 2021-07-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: n-acetylcysteine. 25 participants randomly selected Arm 2: placebo. 25 participants randomly selected
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: Inclusion criteria:

1. Greater than or equal to 18 years of age
2. Meets DSM-V criteria for alcohol use disorder on the SCID-5
3. 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:

1. Lifetime clinical diagnosis of schizophrenia or bipolar disorder
2. Currently receiving medication for the treatment of alcohol use disorder including oral or injectable naltrexone (ReVia, Vivitrol), disulfiram (Antabuse), and acamprosate (Campral).
3. Pregnancy
4. Lack of English fluency sufficient to complete study measures.
5. Trying to get pregnant in the next 4 months.
6. Hospitalized because of alcohol use in the past 12 months.
7. History of seizures or delirium tremens.
8. History of liver disease
9. Diagnosis of a neurocognitive disorder (e.g., dementia, alzheimer's, mental retardation).
10. Individuals who were never enrolled into Addiction Treatment Services

Primary outcomes:
measure: Change in total drinking days
timeFrame: 7 weeks
measure: Change in drinks per drinking day
timeFrame: 7 weeks
Secondary outcomes:
measure: Change in alcohol cue-reactivity
timeFrame: 7 weeks
measure: Change in alcohol demand
timeFrame: 7 weeks
measure: Change in alcohol craving
timeFrame: 7 weeks
Other outcomes:
measure: Change in response inhibition
timeFrame: 7 weeks
measure: Change in working memory
timeFrame: 7 weeks
measure: Change in executive functioning
timeFrame: 7 weeks
measure: Change in depression symptoms
timeFrame: 7 weeks
measure: Change in anxiety symptoms
timeFrame: 7 weeks
measure: Change in anxiety symptoms
timeFrame: 7 weeks
measure: Change in anxiety symptoms
timeFrame: 7 weeks
measure: Change in total marijuana use days
timeFrame: 7 weeks
measure: Change in total cigarette use days
timeFrame: 7 weeks
measure: Change in cigarettes per day
timeFrame: 7 weeks
Locations:
Study officials:
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