A Study of NAC for AUD

Sponsor

Uniformed Services University of the Health Sciences (U.S. Fed)

Overall Status

Not yet recruiting

CT.gov ID

NCT04964843

Collaborator

(none)

Enrollment

Arms

21.1

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Use Disorder	Drug: N-acetylcysteine Drug: Placebo	Phase 2

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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Arm 1: n-acetylcysteine. 25 participants randomly selected Arm 2: placebo. 25 participants randomly selectedArm 1: n-acetylcysteine. 25 participants randomly selected Arm 2: placebo. 25 participants randomly selected

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Double-blind

Primary Purpose:

Treatment

Official Title:

A Pilot Study of N-acetylcysteine for Alcohol Use Disorder

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: N-acetylcysteine

25 participants randomly selected to receive 1500 milligrams of oral n-acetylcysteine twice daily for 7 weeks.

Drug: N-acetylcysteine

N-acetylcysteine is an FDA approved medication that is used to treat acetaminophen overdose.

Placebo Comparator: Placebo

25 participants randomly selected to receive placebo twice daily for 7 weeks.

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Change in total drinking days [7 weeks]
Change in total drinking days will be assessed with the Timeline Follow Back alcohol use assessment
Change in drinks per drinking day [7 weeks]
Change in drinks per drinking day will be assessed with the Timeline Follow Back alcohol use assessment

Secondary Outcome Measures

Change in alcohol cue-reactivity [7 weeks]
Change in alcohol cue-reactivity will be assessed with a task in which participants are exposed to stimuli associated with alcohol
Change in alcohol demand [7 weeks]
Change in alcohol demand will be assessed with the alcohol purchase task
Change in alcohol craving [7 weeks]
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.

Other Outcome Measures

Change in response inhibition [7 weeks]
Change in response inhibition will be assessed with the Stop Signal Task.
Change in working memory [7 weeks]
Change in working memory will be assessed with the N-back task (2 back and 3 back)
Change in executive functioning [7 weeks]
Change in executive functioning will be assessed with the Trail Making Task
Change in depression symptoms [7 weeks]
Change in depression symptoms will be assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS), a 10-item questionnaire assessing depression symptoms. Scores range from 0-60, higher scores indicate more depression symptoms
Change in anxiety symptoms [7 weeks]
Change in anxiety symptoms will be assessed with the Generalized Anxiety Disorder Screener (GAD-7), a 7-item self-report measure assessing symptoms of generalized anxiety. Scores range from 0-21, higher scores indicate more anxiety symptoms.
Change in anxiety symptoms [7 weeks]
Change in anxiety symptoms will be assessed with the Social Interaction Anxiety Scale (SIAS-6), a 6-item measure of social interaction anxiety. Scores range from 0-24 where higher scores indicate higher anxiety.
Change in anxiety symptoms [7 weeks]
Change in anxiety symptoms will be assessed with the Social Phobia Scale (SPS-6), a 6-item measure of social phobia anxiety. Scores range from 0-24 where higher scores indicate higher anxiety.
Change in total marijuana use days [7 weeks]
Change in total marijuana use days will be assessed with the Timeline Follow Back marijuana use assessment in the subset of individuals who use marijuana.
Change in total cigarette use days [7 weeks]
Change in total cigarette use days will be assessed with the Timeline Follow Back cigarette use assessment in the subset of individuals who use cigarettes.
Change in cigarettes per day [7 weeks]
Change in cigarettes per day will be assessed with the Timeline Follow Back cigarette use assessment in the subset of individuals who use cigarettes.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Uniformed Services University of the Health Sciences

Investigators

None specified.

Study Documents (Full-Text)

Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Oct 4, 2021

More Information

Publications

Responsible Party:

Uniformed Services University of the Health Sciences

ClinicalTrials.gov Identifier:

NCT04964843

Other Study ID Numbers:

0000

First Posted:

Jul 16, 2021

Last Update Posted:

May 19, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Study Results

No Results Posted as of May 19, 2022