Effectiveness of N-Acetylcysteine (NAC) in Motivational Enhancement Therapy for Nicotine Addiction

Nicotine Dependence Clinical Trial

Official title:

Effectiveness of N-Acetylcysteine in Motivational Enhancement Therapy for Nicotine Addiction: Study on the Dopaminergic Pathways, Changes in Functional Connectivity of fMRI Bold, and Changes in Smoking Abstinence

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05903014
• Other study ID #: 22-06-0672
• Status: Recruiting
• Phase: Phase 4
• Start date: January 1, 2023
• Est. completion date: December 30, 2023

Study information

• Verified date: June 2023
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to determine the effectiveness of the combination of n-acetylcysteine and motivational enhancement therapy on laboratory improvement in the form of changes in blood nicotine, radiological changes in the form of nerve connectivity on post-therapy frontostriatal fMRI examination and clinical changes in the form of abstinence, withdrawal symptoms and cravings in adult smoker.

Description:

The main question it aims to answer are:

Obtain the effectiveness of combination of n-acetylcysteine and motivational enhancement therapy compared to a combination of motivational enhancement therapy and placebo on nicotine withdrawal symptom scores on nicotine addiction.

Obtaining the effectiveness of the combination of n-acetylcysteine and motivational enhancement therapy compared to the combination of motivational enhancement therapy and placebo on craving symptom scores on nicotine addiction.

Obtain the effectiveness of giving a combination of n-acetylcysteine and motivational enhancement therapy compared to a combination of motivational enhancement therapy and placebo in the incidence of abstinence in nicotine addiction.

Obtain the effectiveness of combination n-acetylcysteine and motivational enhancement therapy compared to a combination of motivational enhancement therapy and placebo on blood nicotine levels in nicotine addiction.

Obtain the effectiveness of combination n-acetylcysteine and motivational enhancement therapy compared to a combination of motivational enhancement therapy and placebo on n-acetylaspartate levels in the brain in nicotine addiction.

Obtain the effectiveness of combination n-acetylcysteine and motivational enhancement therapy compared to a combination of motivational enhancement therapy and placebo on glutamate levels in the brain on nicotine addiction.

Obtain an overview of nerve connectivity in nicotine addiction patient through post-therapy frontostriatal fMRI examination.

Evaluate the side effects and severe side effects of NAC administration on nicotine addiction.

Participants will:

Get blood testing for nicotine in 1st, 6th and 12th weeks Fill the QSU-Brief, MTWS questionnaire every 2 weeks for 12 weeks Get motivational enhancement therapy every 2 weeks for 12 weeks Get fMRI in the 12th week Consume 3600 mg n-acetylcysteine for 12 consecutive weeks (for treatment group) and placebo (for control group) Researchers will compare the laboratory, clinical and radiology improvement in both groups

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: December 30, 2023
• Est. primary completion date: September 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male or female who are active smokers are at least 18 years old and decide to stop smoking

2. Using tobacco cigarettes whether filtered or not

3. Active smoker for at least 6 months

4. Smoke at least 10 cigarettes per day

5. Currently in the preparation or action stage at the stage of changes

6. Able to follow instructions and research procedures

Exclusion Criteria:

Have/ suspected to have a systemic medical disorder or psychiatric disorder requiring acute management Currently using electronic cigarettes Currently using oral glucocorticoids Have an acute gastrointestinal ulcer Pregnant or breastfeeding or planning to become pregnant within the next 6 months Currently consume n-acetylcysteine Have a history of allergic reactions with n-acetylcysteine or its components Get therapy to stop smoking such as bupropion, varenicline or nicotine replacement therapy (NRT)

Related Conditions & MeSH terms

• Behavior, Addictive
• Nicotine Addiction
• Nicotine Dependence
• Tobacco Use Disorder

Intervention

Drug:
• n-acetylcysteine
we give 3600 mg n-acetylcysteine divided twice a day, for 12 weeks

Behavioral:
• Motivational Enhancement Therapy
Motivational enhancement therapy with individual and/or group session to maintain and increase subject's motivation to quit smoking

Locations

Country	Name	City	State
Indonesia	Faculty of Medicine, Universitas Indonesia	Jakarta	DKI Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

References & Publications (9)

Bernardo M, Dodd S, Gama CS, Copolov DL, Dean O, Kohlmann K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI, Berk M. Effects of N-acetylcysteine on substance use in bipolar disorder: A randomised placebo-controlled clinical trial. Acta Neuropsychiatr. 2009 Dec;21(6):285-91. doi: 10.1111/j.1601-5215.2009.00397.x. — View Citation

Froeliger B, McConnell PA, Stankeviciute N, McClure EA, Kalivas PW, Gray KM. The effects of N-Acetylcysteine on frontostriatal resting-state functional connectivity, withdrawal symptoms and smoking abstinence: A double-blind, placebo-controlled fMRI pilot study. Drug Alcohol Depend. 2015 Nov 1;156:234-242. doi: 10.1016/j.drugalcdep.2015.09.021. Epub 2015 Sep 26. — View Citation

Knackstedt LA, LaRowe S, Mardikian P, Malcolm R, Upadhyaya H, Hedden S, Markou A, Kalivas PW. The role of cystine-glutamate exchange in nicotine dependence in rats and humans. Biol Psychiatry. 2009 May 15;65(10):841-5. doi: 10.1016/j.biopsych.2008.10.040. Epub 2008 Dec 21. — View Citation

Machado RCBR, Vargas HO, Baracat MM, Urbano MR, Verri WA Jr, Porcu M, Nunes SOV. N-acetylcysteine as an adjunctive treatment for smoking cessation: a randomized clinical trial. Braz J Psychiatry. 2020 Sep-Oct;42(5):519-526. doi: 10.1590/1516-4446-2019-0753. — View Citation

McClure EA, Baker NL, Gipson CD, Carpenter MJ, Roper AP, Froeliger BE, Kalivas PW, Gray KM. An open-label pilot trial of N-acetylcysteine and varenicline in adult cigarette smokers. Am J Drug Alcohol Abuse. 2015 Jan;41(1):52-6. doi: 10.3109/00952990.2014.933839. Epub 2014 Jul 25. — View Citation

Mottillo S, Filion KB, Belisle P, Joseph L, Gervais A, O'Loughlin J, Paradis G, Pihl R, Pilote L, Rinfret S, Tremblay M, Eisenberg MJ. Behavioural interventions for smoking cessation: a meta-analysis of randomized controlled trials. Eur Heart J. 2009 Mar;30(6):718-30. doi: 10.1093/eurheartj/ehn552. Epub 2008 Dec 24. — View Citation

Prado E, Maes M, Piccoli LG, Baracat M, Barbosa DS, Franco O, Dodd S, Berk M, Vargas Nunes SO. N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study. Redox Rep. 2015 Sep;20(5):215-22. doi: 10.1179/1351000215Y.0000000004. Epub 2015 Mar 2. — View Citation

Schmaal L, Berk L, Hulstijn KP, Cousijn J, Wiers RW, van den Brink W. Efficacy of N-acetylcysteine in the treatment of nicotine dependence: a double-blind placebo-controlled pilot study. Eur Addict Res. 2011;17(4):211-6. doi: 10.1159/000327682. Epub 2011 May 24. — View Citation

Schulte M, Goudriaan AE, Kaag AM, Kooi DP, van den Brink W, Wiers RW, Schmaal L. The effect of N-acetylcysteine on brain glutamate and gamma-aminobutyric acid concentrations and on smoking cessation: A randomized, double-blind, placebo-controlled trial. J Psychopharmacol. 2017 Oct;31(10):1377-1379. doi: 10.1177/0269881117730660. Epub 2017 Sep 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Abstinence	number of patient that have been quick smoking at a specific period of time	week 2
Primary	Rate of Abstinence	number of patient that have been quick smoking at a specific period of time	week 4
Primary	Rate of Abstinence	number of patient that have been quick smoking at a specific period of time	week 6
Primary	Rate of Abstinence	number of patient that have been quick smoking at a specific period of time	week 8
Primary	Rate of Abstinence	number of patient that have been quick smoking at a specific period of time	week 10
Primary	Rate of Abstinence	number of patient that have been quick smoking at a specific period of time	week 12
Primary	Score of Withdrawal Symptoms	Score is assessed with Minnesota Tobacco Withdrawal Scale Questionnaire. Scale: 0-32	week 2
Primary	Score of Withdrawal Symptoms	Score is assessed with Minnesota Tobacco Withdrawal Scale Questionnaire. Scale: 0-32	week 4
Primary	Score of Withdrawal Symptoms	Score is assessed with Minnesota Tobacco Withdrawal Scale Questionnaire. Scale: 0-32	week 6
Primary	Score of Withdrawal Symptoms	Score is assessed with Minnesota Tobacco Withdrawal Scale Questionnaire. Scale: 0-32	week 8
Primary	Score of Withdrawal Symptoms	Score is assessed with Minnesota Tobacco Withdrawal Scale Questionnaire. Scale: 0-32	week 10
Primary	Score of Withdrawal Symptoms	Score is assessed with Minnesota Tobacco Withdrawal Scale Questionnaire. Scale: 0-32	week 12
Primary	Score of Craving Symptoms	Score is assessed with Brief Questionnaire of Smoking Urges Questionnaire. Scale: 10-70	week 2
Primary	Score of Craving Symptoms	Score is assessed with Brief Questionnaire of Smoking Urges Questionnaire. Scale: 10-70	week 4
Primary	Score of Craving Symptoms	Score is assessed with Brief Questionnaire of Smoking Urges Questionnaire. Scale: 10-70	week 6
Primary	Score of Craving Symptoms	Score is assessed with Brief Questionnaire of Smoking Urges Questionnaire. Scale: 10-70	week 8
Primary	Score of Craving Symptoms	Score is assessed with Brief Questionnaire of Smoking Urges Questionnaire. Scale: 10-70	week 10
Primary	Score of Craving Symptoms	Score is assessed with Brief Questionnaire of Smoking Urges Questionnaire. Scale: 10-70	week 12
Primary	Level of blood nicotine	Level of blood nicotine	week 6
Primary	Level of blood nicotine	Level of blood nicotine	week 12
Primary	level of n-acetylaspartate in Magnetic Resonance Spectroscopy (MRS) study	level of n-acetylaspartate in Magnetic Resonance Spectroscopy (MRS) study	week 12
Primary	level of glutamate in Magnetic Resonance Spectroscopy (MRS) study	level of glutamate in Magnetic Resonance Spectroscopy (MRS) study	week 12
Secondary	Side Effect of n-acetylcysteine consumption	Side Effect of n-acetylcysteine consumption	every 2 weeks for 12 weeks