Clinical trial NCT01439828: Clinical Trial of N-acetylcysteine Versus Placebo Efficacy in the Cannabis Withdrawal
Official title: Randomized and Double-blind Clinical Trial of N-acetylcysteine Versus Placebo Efficacy in the Cannabis Withdrawal
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cannabis Dependence
Cannabis Abuse
Keywords: Cannabis
N-Acetylcystein
Dependence
Abuse
Craving
Genetic
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2011-09-23
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Success rate of withdrawal defined by a reduction of at least 50% of the rate of urinary carboxy-THC
timeFrame: at 4 weeks
Secondary outcomes:
measure: The success rate of withdrawal defined by a declarative reduction of at least 50% of the cannabis
timeFrame: at 2, 3 and 6 months
measure: The retention rate of withdrawal
timeFrame: at 6 months
measure: The rate of complete cessation of cannabis use
timeFrame: at 4 weeks and 2, 3 and 6 months.
measure: Phenotypic profile (3 major types)
timeFrame: at Day 28 (end of treatment)
Other outcomes:
Locations:
city: Paris
country: France
facility: Service de Psychiatrie - Hôpital Lariboisière
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Eric GUILLEM, MD
role: PRINCIPAL_INVESTIGATOR
References: