First Episode Schizophrenia and Cannabis-Related Disorder Study

NCT00573287 | Completed Results DMC

• 1 other identifier: MG 62157-02
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

Brief Summary

Many individuals with schizophrenia abuse cannabis at the onset of their illness, portending a poorer course of illness and poorer treatment response. Preliminary evidence suggests that clozapine may uniquely reduce substance use in patients with schizophrenia. The purpose of this study is to establish an effective methodology for studying early treatment with clozapine in patients with co-occurring schizophrenia and cannabis use disorder, while generating pilot data comparing clozapine vs. risperidone on substance use, psychiatric symptoms, side effects, and treatment discontinuation.

Conditions

Cannabis-Related Disorder; Substance-Related Disorders; Schizophrenia; Psychotic Disorders

Keywords

Clozapine, risperidone, first episode,

Outcome Measures

Primary Outcomes (1)

• Number of Participants Demonstrating Improvement in Substance Use

  Based on the small sample size, it was not possible to test the differences between the two groups for statistical significance. Data on cannabis use were gathered weekly using the Timeline Follow-back (TLFB) method. At the end of the study, graphs were plotted showing days of cannabis use per week and rated as "Improved," "Unchanged," or "Worse" by a pair of expert judges. Raters were instructed to rate the graph "Improved" or "Worsened" if it appeared to be \>20% better or worse and to rate it "Unchanged" if there was little or no change (less than \~20%).

  24 weeks

Secondary Outcomes (1)

• Number of Participants Demonstrating Improvement in Psychiatric Symptoms Using the BPRS, CGIS, and SANS at 24 Weeks

  24 weeks

Study Arms (2)

Clozapine

EXPERIMENTAL

clozapine: clozapine--tablets, 12.5-100 mg, daily for 24 weeks

Drug: clozapine

Risperidone

ACTIVE COMPARATOR

risperidone: risperidone--tablets, 0.5-5.0mg daily for 24 weeks

Drug: risperidone

Interventions

clozapine DRUG

clozapine--tabs, 450mg. max, daily, 24 weeks

Also known as: Clozaril

Clozapine

risperidone DRUG

risperidone--tabs, 6mg max, daily, 24 weeks

Also known as: Risperdal

Risperidone

Eligibility Criteria

• Age: 17 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 17 - 45
• Meets Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) criteria for schizophrenia or schizoaffective disorder
• Currently within the first episode of schizophrenia ("First Episode" is defined as having onset with the first evidence of psychotic symptoms by history, and the first episode will have ended if the Clinical Global Impressions Scale (CGI) has been \< 2 and there has been no rating \> 2 on any one of the Brief Psychiatric Rating Scale (BPRS) psychotic items for 6 weeks or longer)
• Meets DSM-IV criteria for cannabis use disorder
• Cannabis use within the five weeks prior to recruitment (screening visit or hospital admission) by self-report (TLFB), collateral report, or drug screen.
• Requires treatment with an antipsychotic medication
• Patients (or guardians) must provide informed consent prior to entry into the study

You may not qualify if:

• Medical contraindications to treatment with clozapine or risperidone, including previous paralytic ileus.
• Cumulative treatment with antipsychotic medication in excess of 16 weeks prior to hospital admission (or case identification if an outpatient), unless waived by the Medication Adjustment Group (MAG)
• History of allergic reaction to clozapine or risperidone
• History of seizure disorder or blood dyscrasia. Note: If patients have a history of seizures, but not a diagnosed seizure disorder, they may be admitted to the study if approved by the MAG.
• Current treatment with clozapine
• Currently pregnant, planning to become pregnant, or unwilling to use an acceptable form of birth control.
• Currently residing in a residential program designed to treat substance use disorders.
• Treatment at baseline with a psychotropic agent proposed to curtail substance use (e.g. disulfiram, naltrexone, valproic acid, topiramate, acamprosate or benzodiazepines) will require a review by the medication adjustment group before entering the client into the study
• Patients who, in the opinion of the investigator, are judged unsuitable to participate in the study (For example, patients who are actively homicidal or have a pending incarceration that would prevent them from participating in the study)
• History of, or current breast cancer
• People who are doing well on current therapy
• Lack of an identifiable primary family/support person, and unable to come to a study site for weekly visits
• Treatment with serotonin re-uptake inhibitors will not be excluded but requires a review by the MAG prior to randomization.
• Patients with current cocaine dependence will require review by the MAG to determine stability for the study.
• Treatment with multiple antipsychotics or long acting injectable antipsychotic at baseline is not excluded, but will be reviewed by the MAG to assess appropriateness for the study.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (5)

New Hampshire Hospital

Concord, New Hampshire, 03301, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

West Central Behavioral Health

Lebanon, New Hampshire, 03766, United States

Location

Mental Health Center of Greater Manchester

Manchester, New Hampshire, 03101, United States

Location

Center for Psychiatric Advancement & Community Council of Nashua

Nashua, New Hampshire, 03060, United States

Location

MeSH Terms

Conditions

Marijuana Abuse; Substance-Related Disorders; Schizophrenia; Psychotic Disorders

Interventions

Clozapine; Risperidone

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Alan I. Green, M.D.
• Organization: Geisel School of Medicine at Dartmouth

alan.i.green@dartmouth.edu

6036507549

Study Officials

• Alan I. Green, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• Doug Noordsy, MD

  Dartmouth-Hitchcock Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 12, 2007
• First Posted: December 14, 2007
• Study Start: June 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2011
• Last Updated: July 23, 2019
• Results First Posted: February 18, 2013

Record last verified: 2019-07

Locations

US (5)