Clozapine for Cannabis Use in Schizophrenia

NCT ID: NCT01639872

Last Updated: 2020-05-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

49 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-01

Study Completion Date

2017-03-29

Brief Summary

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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

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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.

Conditions

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Schizophrenia Cannabis Abuse Cannabis Dependence Dual Diagnosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Clozapine

The blinded CLOZ will be titrated on a recommended standard schedule, supervised by a study physician (or other prescriber) who can make the necessary adjustments to account for symptom control and tolerability. The titration is recommended to begin at 12.5 mg and then increase while the open-label base antipsychotic is tapered with a recommended goal of decreasing the base antipsychotic by 25% each week. If clinically tolerated, the target dose of CLOZ is 400 mg/day.

Group Type EXPERIMENTAL

Clozapine

Intervention Type DRUG

Clozapine: target dose of 400mg per day with a maximum dose of 550mg per day

Risperidone

The blinded RISP will also be titrated in the first weeks, using a titration schedule, with a target dose of 4 mg/day, while the open label base antipsychotic is tapered in a similar fashion.

Group Type ACTIVE_COMPARATOR

Risperidone

Intervention Type DRUG

Clozapine: target dose of 4mg per day with a maximum dose of 6mg per day

Interventions

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Clozapine

Clozapine: target dose of 400mg per day with a maximum dose of 550mg per day

Intervention Type DRUG

Risperidone

Clozapine: target dose of 4mg per day with a maximum dose of 6mg per day

Intervention Type DRUG

Other Intervention Names

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Clozaril Risperdal

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of South Carolina

OTHER

Sponsor Role collaborator

Michigan State University

OTHER

Sponsor Role collaborator

University of Miami

OTHER

Sponsor Role collaborator

University of Massachusetts, Worcester

OTHER

Sponsor Role collaborator

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alan I Green, MD

Role: STUDY_CHAIR

Dartmouth College

Locations

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CNS Network Inc

Garden Grove, California, United States

Site Status

Pacific Research Partners

Oakland, California, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Unversity of Massachusetts Medical School

Worcester, Massachusetts, United States

Site Status

Michigan State University / Cherry Street Health Services

Grand Rapids, Michigan, United States

Site Status

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

University of North Carolina/UNC Center for Excellence in Community Mental Health

Raleigh, North Carolina, United States

Site Status

University of South Carolina

Columbia, South Carolina, United States

Site Status

Rutland Regional Medical Center

Rutland, Vermont, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1R01DA032533-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01DA032533-01A1 D13012

Identifier Type: -

Identifier Source: org_study_id

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