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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2012 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01439828
First received: September 21, 2011
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention Phase
Cannabis Dependence
Cannabis Abuse
Drug: N-acetylcystein
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized and Double-blind Clinical Trial of N-acetylcysteine Versus Placebo Efficacy in the Cannabis Withdrawal

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Success rate of withdrawal defined by a reduction of at least 50% of the rate of urinary carboxy-THC [ Time Frame: at 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The success rate of withdrawal defined by a declarative reduction of at least 50% of the cannabis [ Time Frame: at 2, 3 and 6 months ] [ Designated as safety issue: No ]
  • The retention rate of withdrawal [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • The rate of complete cessation of cannabis use [ Time Frame: at 4 weeks and 2, 3 and 6 months. ] [ Designated as safety issue: No ]
    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

  • Phenotypic profile (3 major types) [ Time Frame: at Day 28 (end of treatment) ] [ Designated as safety issue: No ]
    • 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.


Estimated Enrollment: 150
Study Start Date: February 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01439828

Contacts
Contact: Eric GUILLEM, MD +33 (0) 1 49 95 91 12 eric.guillem@lrb.aphp.fr

Locations
France
Service de Psychiatrie - Hôpital Lariboisière Not yet recruiting
Paris, France, 75010
Contact: Eric GUILLEM, MD    +33 (0)1 49 95 91 12    eric.guillem@lrb.aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Eric GUILLEM, MD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01439828     History of Changes
Other Study ID Numbers: P081120
Study First Received: September 21, 2011
Last Updated: January 18, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Cannabis
N-Acetylcystein
Dependence
Abuse
Craving
Genetic

Additional relevant MeSH terms:
Marijuana Abuse
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on September 16, 2014