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
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Cannabis Abuse
Cannabis Dependence
Dual Diagnosis
Drug: Clozapine
Drug: Risperidone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clozapine for Cannabis Use Disorder in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 132
Study Start Date: April 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clozapine Drug: Clozapine
Clozapine: target dose of 400mg per day with a maximum dose of 550mg per day
Other Name: Clozaril
Active Comparator: Risperidone Drug: Risperidone
Clozapine: target dose of 4mg per day with a maximum dose of 6mg per day
Other Name: Risperdal

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01639872

Contacts
Contact: Alan Green, MD 603-650-7549 alan.i.green@dartmuth.edu
Contact: Christopher OKeefe, MA 603-271-5287 christopher.okeefe@dartmouth.edu

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Nicole Brenson    305-355-8186    nbrenson@med.miami.edu   
Principal Investigator: Philip Harvey, Ph.D.         
United States, Massachusetts
Unversity of Massachusetts Medical School Recruiting
Worcester, Massachusetts, United States, 01605
Contact: Radhika Natarajan    508-856-8323    radhika.natarajan@umassmed.edu   
Principal Investigator: Xiaoduo Fan, M.D.         
Sub-Investigator: Amy Harrington, MD         
United States, Michigan
Michigan State University / Cherry Street Health Services Recruiting
Grand Rapids, Michigan, United States, 49503
Contact: Jacob Gonzales    616-965-8200 ext 7312    JacobGonzales@cherryhealth.com   
Principal Investigator: Eric Achtyes, MD         
United States, New Hampshire
Dartmouth Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Mary Brunette, MD    603-271-7642    mary.brunette@dartmouth.edu   
Contact: Christopher OKeefe, MA    603-271-5287    christopher.okeefe@dartmouth.edu   
Principal Investigator: Alan I Green, MD         
Sub-Investigator: Mary Brunette, MD         
Sub-Investigator: Douglas Noordsy, MD         
United States, South Carolina
University of South Carolina Recruiting
Columbia, South Carolina, United States, 29203
Contact: Allison Dew    803-434-1100    Allison.Dew@uscmed.sc.edu   
Principal Investigator: Meera Narasimhan, MD         
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
University of South Carolina
Michigan State University
University of Miami
University of Massachusetts, Worcester
Investigators
Study Chair: Alan I Green, MD Geisel School of Medicine at Dartmouth
  More Information

No publications provided

Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT01639872     History of Changes
Other Study ID Numbers: 1R01DA032533-01A1
Study First Received: July 11, 2012
Last Updated: August 6, 2014
Health Authority: United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
Schizophrenia
Cannabis Abuse
Cannabis Dependence
Dual Diagnosis
Clozapine
Risperidone

Additional relevant MeSH terms:
Marijuana Abuse
Schizophrenia
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Clozapine
Risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
GABA Antagonists
GABA Agents
Dopamine Antagonists
Dopamine Agents

ClinicalTrials.gov processed this record on August 25, 2014