Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Centre for Addiction and Mental Health
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Bernard Le Foll, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier:
NCT01747850
First received: December 7, 2012
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

The purpose of this study is assess Sativex as a treatment for Cannabis dependence. Initially a pilot study will be conducted in five subjects seeking treatment for cannabis dependence to ensure that our planned self-titration regimen is appropriate using Sativex. This phase will be open label, with no placebo control. Then, there will be a twelve-week, double-blind, placebo-controlled study in male and female subjects seeking treatment for cannabis dependence (n=40). All participants will receive a combination of pharmacotherapy (Sativex Spray or Placebo Spray) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT). The subjects will have to come daily to the centre to assess usage of medication. Following the medication phase, participants will have a follow-up weekly for another four weeks and then monthly until the 6 month follow up visit after the target quit date. The investigators are planning to enroll 45 subjects over the two-year period.


Condition Intervention Phase
Cannabis Dependence
Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy
Drug: Sativex
Drug: Placebo spray
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Sativex Associated With Behavioral-relapse Prevention Strategy as Treatment for Cannabis Dependence

Resource links provided by NLM:


Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • Tolerability and efficacy of intervention [ Time Frame: six months ] [ Designated as safety issue: No ]
    Assessment of tolerability and efficacy will be assessed by determining number of subjects that withdrawal from the study due to SAEs and seven day point prevalence cannabis abstinence one week after medication phase and 6mo follow-up, respectively.


Secondary Outcome Measures:
  • Days of cannabis use [ Time Frame: six months ] [ Designated as safety issue: No ]
    Percentage of days cannabis use over the study duration until 6 month follow-up will be assessed (number of urine/blood samples screened as positive)

  • Withdrawal [ Time Frame: six months ] [ Designated as safety issue: No ]
    Effect of Sativex on withdrawal symptom scores will be assessed

  • Cannabis Craving [ Time Frame: six months ] [ Designated as safety issue: No ]
    Effect of Sativex on cannabis craving will be assessed

  • Cannabis use [ Time Frame: six months ] [ Designated as safety issue: No ]
    Amount of cannabis used over the study duration until 6 month follow-up will be assessed


Estimated Enrollment: 45
Study Start Date: March 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sativex
Intervention consist on Sativex Spray (Δ9-tetrahydrocannabinol/cannabidiol). Study subjects will be randomized in blocks of ten to one of the two groups (Sativex vs. placebo) in a double blind manner. There will be a gradual increase of the maximal allowed dose starting at five sprays per day for the first two days and increasing of five sprays per day until reaching the max number of 42 sprays per day at the end of week 2. There will be a total of 12 weeks of drug exposure. All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement/Cognitive Behavioral Therapy.
Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy
All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.
Drug: Sativex
Study subjects will gradually increase the maximal allowed dose of Sativex starting at five sprays per day for the first two days and increasing of five sprays per day until reaching the max number of 42 sprays maximal per day at end of week 2 (Day 11). The target quit date will be set at Day 21 (but subjects will be allowed to stop using cannabis before if they are willing and able to). The medication treatment phase will then be continued for an additional 9 weeks (the last week will be a reduction phase with the use of Spray that will be decreased by 50% to avoid abrupt withdrawal). Then exposure to medications will be stopped (so there will be a total of 12 weeks medication treatment exposure).
Other Name: delta-9-tetrahydrocannabinol and cannabidiol
Placebo Comparator: Placebo spray
Participants will receive a combination of Placebo spray associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy
Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy
All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.
Drug: Placebo spray
Study subjects will gradually increase the maximal allowed dose of Placebo starting at five sprays per day for the first two days and increasing of five sprays per day until reaching the max number of 42 sprays maximal per day at end of week 2 (Day 11). The target quit date will be set at Day 21 (but subjects will be allowed to stop using cannabis before if they are willing and able to). The Placebo treatment phase will then be continued for an additional 9 weeks (the last week will be a reduction phase with the use of Placebo Spray that will be decreased by 50%). Then exposure to Placebo will be stopped (so there will be a total of 12 weeks Placebo treatment exposure).
Other Name: Ethanol,propylene glycol,and peppermint oil with colors
Experimental: Pilot Study
The first five subjects will be treatment-seekers that fit our inclusion/exclusion criteria and that will be treated open-label. These subjects will be instructed to use the Sativex Spray according to the induction schedule provided above. These first subjects will allow us to determine if our schedule for dosing is appropriate for the subsequent phase of the study.
Behavioral: Motivational Enhancement/Cognitive Behavioral Therapy
All participants will receive a combination of pharmacotherapy (Sativex or Placebo) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy.
Drug: Sativex
Study subjects will gradually increase the maximal allowed dose of Sativex starting at five sprays per day for the first two days and increasing of five sprays per day until reaching the max number of 42 sprays maximal per day at end of week 2 (Day 11). The target quit date will be set at Day 21 (but subjects will be allowed to stop using cannabis before if they are willing and able to). The medication treatment phase will then be continued for an additional 9 weeks (the last week will be a reduction phase with the use of Spray that will be decreased by 50% to avoid abrupt withdrawal). Then exposure to medications will be stopped (so there will be a total of 12 weeks medication treatment exposure).
Other Name: delta-9-tetrahydrocannabinol and cannabidiol

Detailed Description:

In the pilot study subjects will be treated with SATIVEX® (THC/cannabidiol combination in a buccal spray) using the same approach as outlined below for the randomized controlled trial. In the twelve-week, double-blind, placebo-controlled study visits will occur weekly during the medication phase of the study. The medication will be self-titrated over three weeks and a target quit date will be set up at Day 21. There will be a total of 12 weeks of drug exposure. Throughout these 12-weeks, all participants will receive a combination of pharmacotherapy (Sativex Spray or Placebo Spray) associated with a weekly intervention of combined Motivational Enhancement Therapy and Cognitive Behavioral Therapy (MET/CBT) in accordance with the intervention practices shown to be effective in treatment of cannabis dependence. The intervention will be adapted from the Brief Counselling for Marijuana Dependence manual published by the Substance Abuse and Mental Health Services Administration (SAMHSA). At each study visit, vital signs and self-report ratings will be collected. In addition, the subjects will have to come daily to the centre to assess medication usage and will be asked to provide urine sample (two times weekly) and blood sample weekly. As there may be compliance issues, a contingency management approach will be also implemented.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult male or female (gender to be analyzed as a covariate)
  • Understand and willing to comply with study requirements and restrictions
  • Willing to use appropriate contraceptive method throughout the study
  • Otherwise healthy as judged by investigator based on medical history, physical exam, vitals, ECG and labs
  • DSM-IV criteria for current marijuana dependence
  • Report marijuana as primary drug of abuse
  • Report using marijuana at least 5 days a week for at least one month
  • Have marijuana positive urine drug screen
  • Treatment seeking cannabis smoker
  • Smoke less than or equal to the equivalent of 4 joints per day (or four grams per day if participants smokes cannabis in other forms)

Exclusion Criteria:

  • Meets DSM-IV criteria for a current axis I disorder including substance use disorder other than cannabis, nicotine or caffeine dependence.
  • First-degree relative with schizophrenia
  • History of seizures
  • History of cardiovascular disease
  • History of pulmonary disease such as asthma, COPD
  • Clinically significant pathology in oral cavity and poor oral hygiene
  • Known sensitivity to dronabinol, cannabidiol, propylene glycole, ethanol or peppermint oil (used in SATIVEX® buccal spray)
  • Unstable medical conditions
  • Pregnant or breast-feeding
  • Currently taking psychotropic medication with benefit for any other illness than treatment of insomnia,
  • Holding a job that involves driving, operating heavy machines
  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: NCT01747850

Contacts
Contact: Bernard Le Foll, MD PhD 4165358501 ext 34772 bernard.lefoll@camh.ca

Locations
Canada, Ontario
Centre for Addiction and Mental Health Recruiting
Toronto, Ontario, Canada, M5S 2S1
Contact: Bernard Le Foll, MD PhD    4165358501 ext 34772    bernard.lefoll@camh.ca   
Sub-Investigator: Peter Selby, MD         
Sub-Investigator: Jurgen Rehm, PhD         
Sub-Investigator: Marilyn Huestis, PhD         
Sub-Investigator: Benedikt Fischer, PhD         
Sub-Investigator: Lena Quilty, PhD         
Principal Investigator: Bernard Le Foll, MD, PhD         
Sponsors and Collaborators
Centre for Addiction and Mental Health
Investigators
Principal Investigator: Bernard Le Foll, MD, PhD Centre for Addiction and Mental Health
  More Information

Additional Information:
No publications provided

Responsible Party: Bernard Le Foll, Head, Translational Addiction Research Laboratory, Centre for Addiction and Mental Health
ClinicalTrials.gov Identifier: NCT01747850     History of Changes
Other Study ID Numbers: 144/2011, R21DA031906
Study First Received: December 7, 2012
Last Updated: June 26, 2014
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Marijuana Abuse
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Dronabinol
Analgesics
Analgesics, Non-Narcotic
Cannabinoid Receptor Agonists
Cannabinoid Receptor Modulators
Central Nervous System Agents
Hallucinogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014