CARE Study: Improving Treatment for the Most Severely Ill With Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00272584
Recruitment Status : Completed
First Posted : January 6, 2006
Last Update Posted : May 8, 2006
Information provided by:
University of British Columbia

Brief Summary:
This is a 9 week, multicentre, randomized, double-blind, placebo-controlled trial with two parallel groups. There is also an open-label extension phase of 18 weeks. Both medications to be used in the study, clozapine and risperidone, are fully approved for the treatment of schizophrenia.

Condition or disease Intervention/treatment Phase
Psychosis, Schizophrenia Drug: Risperidone Phase 4

Detailed Description:

Subjects may be inpatients or outpatients. All subjects will be treated throughout the study with clozapine, at a dose of 400 mg or more, unless limited by side effects. After screening, subjects will be augmented with placebo for 7 days. Any subject with a reduction in PANSS total score of 20% or greater will be discontinued from the study. Beginning on day 8, subjects will be randomized to continued augmentation of clozapine with placebo, or to augmentation with risperidone. The initial daily dose of risperidone will be 1.0 mg, increased in 1.0 mg increments to a total of 3.0 mg/day over a two week period. Subjects unable to tolerate at least one tablet of study medication will be dropped from the study. At the end of 8 weeks following randomization, at the choice of the investigator, open-label risperidone augmentation can be started.

The primary outcome measure is the PANSS total score at week 9. Subjects will be classified as responders if the improvement in PANSS total score is 20% or greater, and the proportion of responders in each group will be determined. Complementary outcome measures will be the CGI severity score, CGI improvement score, and SOFAS score. Safety and tolerance will be assessed by reports of adverse events and clinically significant changes in vital signs, weight, waist circumference, extrapyramidal side effects, metabolic and hematological measures.

Study Type : Interventional  (Clinical Trial)
Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: International Study of Improving Treatment for the Most Severely Ill With Schizophrenia
Study Start Date : June 2001
Study Completion Date : January 2004

Resource links provided by the National Library of Medicine

Drug Information available for: Risperidone
U.S. FDA Resources

Primary Outcome Measures :
  1. For 100 subjects with incomplete response to adequate treatment with clozapine, the primary objective is to determine if risperidone augmentation of clozapine is superior to augmentation with placebo, using the outcome measure of total PANSS score

Secondary Outcome Measures :
  1. Additional outcome measures will be: proportion of subjects with a 20% or greater reduction in PANSS total score, CGI severity score, CGI improvement score and SOFAS score.
  2. To assess the safety of risperidone augmentation, severity of extrapyramidal side effects, metabolic measures, and general side effects will be studied. Hematological monitoring will be carried out.
  3. To determine if risperidone augmentation has effects on cognition, a neuropsychological test battery will be carried out.
  4. The predictive value of neurocognitive testing, and DNA analysis for results of risperidone augmentation will be studied.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subjects treated with clozapine for the indication of poor response to other antipsychotic medications.
  • Treatment with clozapine is at a stable dose for at least 12 weeks. Dose must be 400 mg/day or more, unless side effects limited increase of dose.

Exclusion Criteria:

  • Subjects with significant alcohol or substance abuse in the past 3 months.
  • Subjects with a previous trial of risperidone augmentation of clozapine
  • Subjects who are pregnant, breast-feeding, or women of child-bearing potential not using adequate contraception
  • Subjects requiring treatment with anticonvulsants.
  • Subjects with known hypersensitivity or allergy to risperidone.
  • Subjects with hematological or other contraindications to continued clozapine treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00272584

Canada, British Columbia
UBC Hospital
Vancouver, British Columbia, Canada
Sponsors and Collaborators
University of British Columbia
Principal Investigator: William Honer, MD University of British Columbia

Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00272584     History of Changes
Other Study ID Numbers: C0-0280
First Posted: January 6, 2006    Key Record Dates
Last Update Posted: May 8, 2006
Last Verified: January 2006

Keywords provided by University of British Columbia:
Psychosis, schizophrenia, schizoaffective, clozapine, risperidone

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents