Clozapine for Cannabis Use in Schizophrenia (CLOCS)
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.
|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|
- 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.
- 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.
|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)|
Clozapine: target dose of 400mg per day with a maximum dose of 550mg per day
Other Name: Clozaril
|Active Comparator: Risperidone||
Clozapine: target dose of 4mg per day with a maximum dose of 6mg per day
Other Name: Risperdal
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01639872
|Contact: Alan Green, MDfirstname.lastname@example.org|
|Contact: Christopher OKeefe, MAemail@example.com|
|United States, Florida|
|University of Miami||Recruiting|
|Miami, Florida, United States, 33136|
|Contact: Nicole Brenson 305-355-8186 firstname.lastname@example.org|
|Principal Investigator: Philip Harvey, Ph.D.|
|United States, Massachusetts|
|Unversity of Massachusetts Medical School||Recruiting|
|Worcester, Massachusetts, United States, 01605|
|Contact: Matthew Goodnow 508-856-2494 Matthew.Goodnow@umassmed.edu|
|Principal Investigator: Xiaoduo Fan, M.D.|
|Sub-Investigator: Amy Harrington, MD|
|United States, New Hampshire|
|Dartmouth Hitchcock Medical Center||Recruiting|
|Lebanon, New Hampshire, United States, 03756|
|Contact: Mary Brunette, MD 603-271-7642 email@example.com|
|Contact: Christopher OKeefe, MA 603-271-5287 firstname.lastname@example.org|
|Principal Investigator: Alan I Green, MD|
|Sub-Investigator: Mary Brunette, MD|
|Sub-Investigator: Douglas Noordsy, MD|
|United States, New York|
|The Zucker Hillside Hospital, Long island Jewish Medical Center||Recruiting|
|Glen Oaks, New York, United States, 11004|
|Contact: Raphael Braga, MD 718-470-4801 email@example.com|
|Principal Investigator: Raphael Braga, 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|
|Study Chair:||Alan I Green, MD||Geisel School of Medicine at Dartmouth|