Clozapine for Cannabis Use in Schizophrenia (CLOCS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Dartmouth-Hitchcock Medical Center
Sponsor:
Collaborators:
University of South Carolina
Michigan State University
University of Miami
University of Massachusetts, Worcester
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT01639872
First received: July 11, 2012
Last updated: August 6, 2014
Last verified: August 2014

July 11, 2012
August 6, 2014
April 2013
October 2016   (final data collection date for primary outcome measure)
  • Intensity of cannabis use [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
    Intensity of cannabis use will be assessed by the amount of cannabis consumed each week
  • Frequency of cannabis use [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
    Frequency of cannabis use will be assessed by the days of use per week.
Same as current
Complete list of historical versions of study NCT01639872 on ClinicalTrials.gov Archive Site
  • Symptoms of Schizophrenia [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]
    Symptoms of schizophrenia will be measured using the scores on standardized assessments, including the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Negative Symptoms, and the Clinical Global Inventory
  • Quality of Life [ Time Frame: Monthly for three months ] [ Designated as safety issue: No ]
    Quality of life will be assessed based on scores on the Quality of Life scale and the "subjective section" from the Quality of Life Interview
  • Neuropsychological functioning [ Time Frame: Every 6 weeks for three months ] [ Designated as safety issue: No ]
    Neuropsychological functioning will be assessed using the MATRICS Consensus Cognitive Battery;
  • Reward responsiveness [ Time Frame: Every 6 weeks for three months ] [ Designated as safety issue: No ]
    We will assess reward responsiveness using the computerized Probabilistic Reward Task. This task measures the extent to which a participant biases their responding toward a more rewarded versus less rewarded stimulus consistent with the view that frequency of responding is increased toward reinforcers.
Same as current
Not Provided
Not Provided
 
Clozapine for Cannabis Use in Schizophrenia
Clozapine for Cannabis Use Disorder in Schizophrenia

Many individuals with schizophrenia also suffer from marijuana addiction that worsens their problems related to schizophrenia. Most of the medications prescribed for schizophrenia have no effect on reducing marijuana use. Preliminary data suggests that clozapine, an atypical antipsychotic, may limit marijuana use in people diagnosed with schizophrenia, but it is not commonly used due to its side effects and is reserved for people who do not respond to other antipsychotic medications.

In the proposed study, 132 individuals who are diagnosed with both schizophrenia and a cannabis use disorder will be randomized to a 12-week treatment course with either clozapine or risperidone (another commonly prescribed antipsychotic medication) to test the hypothesis that patient treated with clozapine will have decreased cannabis use as compared to patients treated with risperidone.

Should this study indicate that clozapine will lessen marijuana use in persons diagnosed with schizophrenia more than risperidone, it will provide evidence needed to begin to shift clinical practice toward its use in this population.

Cannabis use disorder (CUD), which is up to ten times more common in patients with schizophrenia (SCZ) than in the general population, worsens the course of this severe psychiatric disorder. Since SCZ occurs in 1% of the population, the co-occurrence of CUD in 13% to 42% of people with this disorder presents society with an important public health problem. Unfortunately, most antipsychotics available for treatment of patients with SCZ do not appear to limit their cannabis use. Moreover, the one antipsychotic that preliminary data suggest may well limit cannabis use in these patients, clozapine (CLOZ), is not used for this purpose; it is reserved for patients whose psychosis is treatment resistant.

The overarching idea behind this proposal, however, is that CLOZ's use is being unreasonably restricted and should be made more widely available for patients with SCZ who have a co-occurring CUD but whose psychosis is not necessarily treatment resistant. This notion is supported by our preliminary clinical and animal data on the effects of CLOZ, as well as our neurobiological model of the basis of cannabis use in patients with SCZ that provides a pharmacologic rationale for this effect of CLOZ.

Even given all the arguments favoring the potential benefits of CLOZ in patients with SCZ and CUD, however, its side effect profile will likely limit its use until a fully powered study demonstrates its ability to decrease cannabis use in patients with SCZ. This proposal aims to launch such a study. If, as we hypothesize, this study confirms and extends our previous preliminary data of the effects of CLOZ in patients with SCZ and CUD, it will provide a strong impetus to expand the use of CLOZ in this population.

In the proposed study, 132 patients who are comorbid for both SCZ and CUD will be randomized to a 12-week treatment course with either CLOZ or risperidone (RISP) to test the hypothesis that patients treated with CLOZ will have decreased cannabis use as compared to patients treated with RISP. In addition, the study will determine whether patients treated with CLOZ will have improvements in psychiatric symptoms, quality of life neuropsychological functions as compared to those taking RISP. We will also explore whether patients taking CLOZ show improved reward responsiveness as compared to those taking RISP. Finally, this study will explore whether those patients with the val/val genotype at the COMT Val158Met locus are more likely to decrease cannabis use during CLOZ treatment than are those without the val/val COMT genotype.

Should this study indicate that CLOZ will lessen cannabis use in patients with SCZ more than RISP, it will provide evidence needed to begin to shift clinical practice toward its use in these patients.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Schizophrenia
  • Cannabis Abuse
  • Cannabis Dependence
  • Dual Diagnosis
  • Drug: Clozapine
    Clozapine: target dose of 400mg per day with a maximum dose of 550mg per day
    Other Name: Clozaril
  • Drug: Risperidone
    Clozapine: target dose of 4mg per day with a maximum dose of 6mg per day
    Other Name: Risperdal
  • Experimental: Clozapine
    Intervention: Drug: Clozapine
  • Active Comparator: Risperidone
    Intervention: Drug: Risperidone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
132
October 2017
October 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Clnical diagnosis of schizophrenia
  • Clinical diagnosis of a cannabis use disorder (abuse or dependence)

Exclusion Criteria:

  • Pregnant,trying to become pregnant or nursing
  • History of a seizure disorder
  • Current treatment with clozapine or risperidone
  • Contraindication to treatment with clozapine or risperidone
Both
18 Years to 55 Years
No
Contact: Alan Green, MD 603-650-7549 alan.i.green@dartmuth.edu
Contact: Christopher OKeefe, MA 603-271-5287 christopher.okeefe@dartmouth.edu
United States
 
NCT01639872
1R01DA032533-01A1
Yes
Dartmouth-Hitchcock Medical Center
Dartmouth-Hitchcock Medical Center
  • University of South Carolina
  • Michigan State University
  • University of Miami
  • University of Massachusetts, Worcester
Study Chair: Alan I Green, MD Geisel School of Medicine at Dartmouth
Dartmouth-Hitchcock Medical Center
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP