Clozapine for Cannabis Use in Schizophrenia
Information source: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia; Cannabis Abuse; Cannabis Dependence; Dual Diagnosis
Intervention: Clozapine (Drug); Risperidone (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Dartmouth-Hitchcock Medical Center Official(s) and/or principal investigator(s): Alan I Green, MD, Study Chair, Affiliation: Geisel School of Medicine at Dartmouth
Overall contact: Alan Green, MD, Phone: 603-650-7549, Email: alan.i.green@dartmuth.edu
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.
Clinical Details
Official title: Clozapine for Cannabis Use Disorder in Schizophrenia
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Intensity of cannabis useFrequency of cannabis use
Secondary outcome: Symptoms of SchizophreniaQuality of Life Neuropsychological functioning Reward responsiveness
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
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
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
Locations and Contacts
Alan Green, MD, Phone: 603-650-7549, Email: alan.i.green@dartmuth.edu
University of Miami, Miami, Florida 33136, United States; Recruiting Nicole Brenson, Phone: 305-355-8186, Email: nbrenson@med.miami.edu Philip Harvey, Ph.D., Principal Investigator
Unversity of Massachusetts Medical School, Worcester, Massachusetts 01605, United States; Recruiting Radhika Natarajan, Phone: 508-856-8323, Email: radhika.natarajan@umassmed.edu Xiaoduo Fan, M.D., Principal Investigator Amy Harrington, MD, Sub-Investigator
Michigan State University / Cherry Street Health Services, Grand Rapids, Michigan 49503, United States; Recruiting Jacob Gonzales, Phone: 616-965-8200, Ext: 7312, Email: JacobGonzales@cherryhealth.com Eric Achtyes, MD, Principal Investigator
University of Minnesota / Ambulatory Research Center, Minneapolis, Minnesota 55454, United States; Recruiting Victoria Patrick, Phone: 612-273-9857, Email: vpatrick@umn.edu Charles Schulz, MD, Principal Investigator
Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States; Recruiting Mary Brunette, MD, Phone: 603-271-7642, Email: mary.brunette@dartmouth.edu Christopher OKeefe, MA, Phone: 603-271-5287, Email: christopher.okeefe@dartmouth.edu Alan I Green, MD, Principal Investigator Mary Brunette, MD, Sub-Investigator Douglas Noordsy, MD, Sub-Investigator
University of North Carolina/UNC Center for Excellence in Community Mental Health, Raleigh, North Carolina 27610, United States; Recruiting Tonya Elliot, Phone: 919-966-3915, Email: tlelliot@ad.unc.edu Fred Jarskog, MD, Principal Investigator
University of South Carolina, Columbia, South Carolina 29203, United States; Recruiting Shalon Howard, Phone: 803-434-1642, Email: Shalon.Howard@uscmed.sc.edu Meera Narasimhan, MD, Principal Investigator
Rutland Regional Medical Center, Rutland, Vermont 05701, United States; Recruiting Laurie Waterman, Phone: 603-653-1802, Email: Laurie.A.Waterman@Hitchcock.org Gordon Frankle, MD, Principal Investigator
Additional Information
Starting date: April 2013
Last updated: April 8, 2015
|