Clinical Trial of N-acetylcysteine Versus Placebo Efficacy in the Cannabis Withdrawal (MUCOCRAV)

Randomized and Double-blind Clinical Trial of N-acetylcysteine Versus Placebo Efficacy in the Cannabis Withdrawal

The primary purpose is to assess the efficacy in human of N-acetylcysteine versus placebo during 4 weeks in cannabis withdrawal.

Study Overview

• Status: Terminated
• Conditions: Cannabis Dependence; Cannabis Abuse
• Intervention / Treatment: Drug: N-acetylcystein

Detailed Description

Introduction:There are few clinical trials on pharmacotherapies in marijuana dependence. There is no randomized and double-blind trial on N-acetylcysteine efficacy in marijuana withdrawal.Aims:The first aim is to assess the efficacy in human (n=150 outpatients) of N-acetylcysteine versus placebo during 4 weeks in cannabis withdrawal.The secondary aims are:a-Assessing the abstinence during the next 5 months of follow-up.b-Assessing the correlations between genetic characteristics: cytochrome CYP2C9 and CYP3A4, CNR1 receptor, Fatty Amide Hydroxylase (FAAH), dopamine DAT transporters and Catechol-O-MéthylTransférase (COMT); and three phenotypes : 1. cannabis level consumption, 2. cannabis abuse and dependence (DSM-IV), and 3. cannabis withdrawal.c-Assessing tobacco consumption (Fagerström test), NICOTINIQUE receptor CHRA3 and cannabis quitting success.Subjects:150 cannabis outpatients, seeking treatment in LARIBOISIERE hospital cannabis setting, to cut down their cannabis use.Inclusion criteria: > 18 year old, not pregnant or breast feeding, cannabis abuse or dependence diagnosis (DSM-IV), acceptance of the trial and consent signed, validated by ethic committee.Methods:Randomized and double-blind trial.Visit 0: Clinical assessment and trial presentation, Validate inclusion and non- inclusion criteria.Visit 1: Consent signed. Blood and urine analysis. Questionnaires assessing cannabis and tobacco's craving.NAC and placebo doses will be increased if craving decreases <25% compared to previous visit. The doses start at 200 mg x 4/24h to 800 mg x 4/24h.Visit 2 to 5: Medication safety and cannabis craving and withdrawal assessment during 4 weeks.Visit 5: Blood and urine analysis.Visit 6 to 8: abstinence assessment during 5 months.Goals:Efficacy assessment of N-Acetylcysteine in cannabis withdrawal and abstinence compared to placebo. Assessment of NAC efficacy in cannabis craving. The length of the study is 6 months to evaluate abstinence persistence. Evaluation of clinical, biological and genetic factors associated with abstinence success.Statistic :Sample size : A two group continuity corrected c2 test with a 0.050 two-sided significance level will have 80% power to detect the difference between a Group 1 proportion, p1, of 0.250 and a Group 2 proportion, p2, of 0.500 (odds ratio of 3.000) when the sample size in each group is 66. Taking into account a rate of lost of follow-up around 15 % the total sample size of the study has been fixed at N= 150 patients.Main criterion and binary secondary criteria will be analysed by Chi-square tests or Fisher's exact probability test. Relationships between genotype and phenotypes will be analysed by multivariate logistic models

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Service de Psychiatrie - Hôpital Lariboisière

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• > 18 year old
• Not pregnant or breast feeding
• Cannabis abuse or dependence diagnosis (DSM-IV)
• Acceptance of the trial and consent signed, validated by ethic committee
• Patient affiliated to social insurance care

Exclusion Criteria:

• Contraindication to N-acetylcystein : allergic to N-acetylcystein, severe allergic illness, PHENYLCETONURIA, lactose intolerance, gastro-duodenal ulcer.
• Severe somatic disease not stabilized : diabetes, epilepsia, recent myocardial infarcts, asthma.
• Severe mental disease not stabilized : schizophrenia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental : N-acetylcystein; N-acetylcystein and placebo doses will be increased if craving decreases <25% compared to the previous visit. The doses start at 200 mg x 4/24h to 800 mg x 4/24h	Drug: N-acetylcystein; Visit 1: Consent signed. Blood and urine analysis. Questionnaires assessing cannabis and tobacco's craving.N-acetylcystein and placebo doses will be increased if craving decreases <25% compared to previous visit.The doses start at 200 mg x 4/24h to 800 mg x 4/24h.Visit 2 to 5: Medication safety and cannabis craving and withdrawal assessment during 4 weeks.
Placebo Comparator: Placebo Comparator; N-acetylcystein and placebo doses will be increased if craving decreases <25% compared to the previous visit. The doses start at 200 mg x 4/24h to 800 mg x 4/24h	Drug: N-acetylcystein; Visit 1: Consent signed. Blood and urine analysis. Questionnaires assessing cannabis and tobacco's craving.N-acetylcystein and placebo doses will be increased if craving decreases <25% compared to previous visit.The doses start at 200 mg x 4/24h to 800 mg x 4/24h.Visit 2 to 5: Medication safety and cannabis craving and withdrawal assessment during 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Success rate of withdrawal defined by a reduction of at least 50% of the rate of urinary carboxy-THC	at 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The success rate of withdrawal defined by a declarative reduction of at least 50% of the cannabis		at 2, 3 and 6 months
The retention rate of withdrawal		at 6 months
The rate of complete cessation of cannabis use	Declarative clinical criteria by the patient and validated at D28 by the decrease of at least 50% of the report of the dosage of the report CarboxyTHC / creatinine	at 4 weeks and 2, 3 and 6 months.
Phenotypic profile (3 major types)	The amount of cannabis and THC consumed with use of the upper quartile to define a high consumption and the lowest quartile to define the weak consumer; Dependence and abuse according to DSM IV criteria;; Withdrawal syndrome in dependent patients according to DSM IV and the scale of MJQQ Gorelick.	at Day 28 (end of treatment)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Eric GUILLEM, MD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: September 22, 2011
• First Posted (Estimate): September 23, 2011

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 14, 2021
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Genetic; Dependence; Craving; Cannabis; Abuse; N-Acetylcystein
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse
• Other Study ID Numbers: P081120