Randomized and Double-blind Clinical Trial of N-acetylcysteine Versus Placebo Efficacy in the Cannabis Withdrawal
Overview
- Phase
- Phase 2
- Intervention
- N-acetylcystein
- Conditions
- Cannabis Dependence
- Sponsor
- Assistance Publique - Hôpitaux de Paris
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Success rate of withdrawal defined by a reduction of at least 50% of the rate of urinary carboxy-THC
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
The primary purpose is to assess the efficacy in human of N-acetylcysteine versus placebo during 4 weeks in cannabis withdrawal.
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
Investigators
Eligibility Criteria
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.
Arms & Interventions
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
Intervention: N-acetylcystein
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
Intervention: N-acetylcystein
Outcomes
Primary Outcomes
Success rate of withdrawal defined by a reduction of at least 50% of the rate of urinary carboxy-THC
Time Frame: at 4 weeks
Secondary Outcomes
- Phenotypic profile (3 major types)(at Day 28 (end of treatment))
- 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(at 4 weeks and 2, 3 and 6 months.)