Clozapine for Cannabis Use in Schizophrenia

Schizophrenia Clinical Trial

— CLOCS  

Official title:

Clozapine for Cannabis Use Disorder in Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01639872
• Other study ID #: 1R01DA032533-01A1 D13012
• Secondary ID: 1R01DA032533-01A
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2013
• Est. completion date: March 29, 2017

Study information

• Verified date: April 2020
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 Catechol-O-methyltransferase (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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: March 29, 2017
• Est. primary completion date: March 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Cannabis Abuse
• Cannabis Dependence
• Dual Diagnosis
• Marijuana Abuse
• Schizophrenia

Intervention

Drug:
• Clozapine
Clozapine: target dose of 400mg per day with a maximum dose of 550mg per day
• Risperidone
Clozapine: target dose of 4mg per day with a maximum dose of 6mg per day

Locations

Country	Name	City	State
United States	University of South Carolina	Columbia	South Carolina
United States	CNS Network Inc	Garden Grove	California
United States	Michigan State University / Cherry Street Health Services	Grand Rapids	Michigan
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Miami	Miami	Florida
United States	Pacific Research Partners	Oakland	California
United States	University of North Carolina/UNC Center for Excellence in Community Mental Health	Raleigh	North Carolina
United States	Rutland Regional Medical Center	Rutland	Vermont
United States	Unversity of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (5)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center	Michigan State University, University of Massachusetts, Worcester, University of Miami, University of South Carolina

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Average Over Time of Intensity of Cannabis Use (Used to Evaluate Treatment Efficacy)	Intensity of cannabis use is obtained each week retrospectively as the number of joints smoked during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.	12 weeks
Primary	Average Over Time of Frequency of Cannabis Use	Frequency of cannabis use is obtained each week retrospectively as the number of days of cannabis use during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.	12 weeks