A Study of NAC for AUD

NCT04964843 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 0000
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Change in alcohol cue-reactivity

  7 weeks

• Change in alcohol demand

  7 weeks

• Change in alcohol craving

  7 weeks

Other Outcomes (10)

• Change in response inhibition

  7 weeks

• Change in working memory

  7 weeks

• Change in executive functioning

  7 weeks

Study Arms (2)

N-acetylcysteine

EXPERIMENTAL

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

Drug: N-acetylcysteine

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

N-acetylcysteine DRUG

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

N-acetylcysteine

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Uniformed Services University of the Health Sciences: lead

Related Publications (25)

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• Reyes RC, Cittolin-Santos GF, Kim JE, Won SJ, Brennan-Minnella AM, Katz M, Glass GA, Swanson RA. Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid. Neurotherapeutics. 2016 Jan;13(1):217-25. doi: 10.1007/s13311-015-0404-4.

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• Lebourgeois S, Gonzalez-Marin MC, Jeanblanc J, Naassila M, Vilpoux C. Effect of N-acetylcysteine on motivation, seeking and relapse to ethanol self-administration. Addict Biol. 2018 Mar;23(2):643-652. doi: 10.1111/adb.12521. Epub 2017 May 30.

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• Schneider R Jr, Santos CF, Clarimundo V, Dalmaz C, Elisabetsky E, Gomez R. N-acetylcysteine prevents behavioral and biochemical changes induced by alcohol cessation in rats. Alcohol. 2015 May;49(3):259-63. doi: 10.1016/j.alcohol.2015.01.009. Epub 2015 Feb 13.

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• Quintanilla ME, Rivera-Meza M, Berrios-Carcamo P, Salinas-Luypaert C, Herrera-Marschitz M, Israel Y. Beyond the "First Hit": Marked Inhibition by N-Acetyl Cysteine of Chronic Ethanol Intake But Not of Early Ethanol Intake. Parallel Effects on Ethanol-Induced Saccharin Motivation. Alcohol Clin Exp Res. 2016 May;40(5):1044-51. doi: 10.1111/acer.13031. Epub 2016 Apr 8.

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• Schneider R Jr, Bandiera S, Souza DG, Bellaver B, Caletti G, Quincozes-Santos A, Elisabetsky E, Gomez R. N-acetylcysteine Prevents Alcohol Related Neuroinflammation in Rats. Neurochem Res. 2017 Aug;42(8):2135-2141. doi: 10.1007/s11064-017-2218-8. Epub 2017 Mar 16.

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• Morley KC, Baillie A, Van Den Brink W, Chitty KE, Brady K, Back SE, Seth D, Sutherland G, Leggio L, Haber PS. N-acetyl cysteine in the treatment of alcohol use disorder in patients with liver disease: Rationale for further research. Expert Opin Investig Drugs. 2018 Aug;27(8):667-675. doi: 10.1080/13543784.2018.1501471. Epub 2018 Aug 1.

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• Squeglia LM, Baker NL, McClure EA, Tomko RL, Adisetiyo V, Gray KM. Alcohol use during a trial of N-acetylcysteine for adolescent marijuana cessation. Addict Behav. 2016 Dec;63:172-7. doi: 10.1016/j.addbeh.2016.08.001. Epub 2016 Aug 4.

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• Squeglia LM, Tomko RL, Baker NL, McClure EA, Book GA, Gray KM. The effect of N-acetylcysteine on alcohol use during a cannabis cessation trial. Drug Alcohol Depend. 2018 Apr 1;185:17-22. doi: 10.1016/j.drugalcdep.2017.12.005. Epub 2018 Feb 1.

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• Gray KM, Carpenter MJ, Baker NL, DeSantis SM, Kryway E, Hartwell KJ, McRae-Clark AL, Brady KT. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am J Psychiatry. 2012 Aug;169(8):805-12. doi: 10.1176/appi.ajp.2012.12010055.

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• Gray KM, Sonne SC, McClure EA, Ghitza UE, Matthews AG, McRae-Clark AL, Carroll KM, Potter JS, Wiest K, Mooney LJ, Hasson A, Walsh SL, Lofwall MR, Babalonis S, Lindblad RW, Sparenborg S, Wahle A, King JS, Baker NL, Tomko RL, Haynes LF, Vandrey RG, Levin FR. A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend. 2017 Aug 1;177:249-257. doi: 10.1016/j.drugalcdep.2017.04.020. Epub 2017 Jun 10.

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MeSH Terms

Conditions

Alcoholism

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: June 17, 2021
• First Posted: July 16, 2021
• Study Start: April 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: July 21, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share