Clozapine for Cannabis Use in Schizophrenia (CLOCS)

Tracking Information
First Submitted Date ICMJE	July 11, 2012
First Posted Date ICMJE	July 13, 2012
Last Update Posted Date	March 23, 2018
Actual Study Start Date ICMJE	May 1, 2013
Actual Primary Completion Date	March 29, 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 12, 2012)	Intensity of cannabis use [ Time Frame: up to 12 weeks ]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 ]Frequency of cannabis use will be assessed by the days of use per week.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01639872 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 12, 2012)	Symptoms of Schizophrenia [ Time Frame: up to 12 weeks ]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 ]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 ]Neuropsychological functioning will be assessed using the MATRICS Consensus Cognitive Battery;; Reward responsiveness [ Time Frame: Every 6 weeks for three months ]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.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Clozapine for Cannabis Use in Schizophrenia
Official Title ICMJE	Clozapine for Cannabis Use Disorder in Schizophrenia
Brief Summary	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.
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.
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Schizophrenia; Cannabis Abuse; Cannabis Dependence; Dual Diagnosis
Intervention ICMJE	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
Study Arms	Experimental: Clozapine Intervention: Drug: Clozapine; Active Comparator: Risperidone Intervention: Drug: Risperidone
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 21, 2018)	50
Original Estimated Enrollment ICMJE; (submitted: July 12, 2012)	132
Actual Study Completion Date	March 29, 2017
Actual Primary Completion Date	March 29, 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Clinical 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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 55 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01639872
Other Study ID Numbers ICMJE	1R01DA032533-01A1( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Alan Green, Dartmouth-Hitchcock Medical Center
Study Sponsor ICMJE	Dartmouth-Hitchcock Medical Center
Collaborators ICMJE	University of South Carolina; Michigan State University; University of Miami; University of Massachusetts, Worcester
Investigators ICMJE	Study Chair: Alan I Green, MD Dartmouth College
PRS Account	Dartmouth-Hitchcock Medical Center
Verification Date	March 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP