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

Cannabis Dependence Clinical Trial

— MUCOCRAV  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01439828
• Other study ID #: P081120
• Status: Terminated
• Phase: Phase 2
• Start date: February 2012
• Est. completion date: February 2015

Study information

• Verified date: January 2012
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: February 2015
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cannabis Abuse
• Cannabis Dependence
• Marijuana Abuse

Intervention

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.

Locations

Country	Name	City	State
France	Service de Psychiatrie - Hôpital Lariboisière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Success rate of withdrawal defined by a reduction of at least 50% of the rate of urinary carboxy-THC		at 4 weeks
Secondary	The success rate of withdrawal defined by a declarative reduction of at least 50% of the cannabis		at 2, 3 and 6 months
Secondary	The retention rate of withdrawal		at 6 months
Secondary	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.
Secondary	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)