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Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine

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ClinicalTrials.gov Identifier: NCT00056498
Recruitment Status : Completed
First Posted : March 17, 2003
Results First Posted : July 16, 2012
Last Update Posted : February 15, 2018
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
Ortho-McNeil Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Robert W. Buchanan, University of Maryland

Brief Summary:
This study will determine whether adding the drug risperidone (Risperdal®) is more effective than placebo in treating schizophrenic patients who are taking the drug clozapine.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Placebo Drug: Risperdal Phase 4

Detailed Description:

Clozapine is the only antipsychotic drug that has been approved for treatment resistant patients with schizophrenia. However, up to 50% of patients treated with clozapine fail to respond and continue to exhibit clinically significant residual positive and negative symptoms and cognitive impairments. An emerging trend in treatment is the addition of a second antipsychotic drug. This study will determine if risperidone when given as adjunctive treatment is more effective than placebo in treating schizophrenic patients failing clozapine therapy.

Participants are randomly assigned to add either adjunctive risperidone or placebo to their current clozapine treatment in a single, daily dose for 16 weeks. Positive and negative symptoms, cognitive impairments, side effects of the treatment, anxiety, depression, hostility symptoms, and quality of life are assessed. Neurological tests, self administered questionnaires, and interviews are used to assess patients.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clozapine Treatment of Schizophrenic Patients
Study Start Date : December 2001
Actual Primary Completion Date : December 2007
Actual Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Active
Participants assigned to risperidone
Drug: Risperdal
Risperdal 4 mg per day for 16 weeks
Other Name: Risperidone
Placebo Comparator: Placebo
Participants assigned to placebo
Drug: Placebo
Placebo capsule daily for 16 weeks



Primary Outcome Measures :
  1. Positive Symptom Item Scores by Week and Treatment Group [ Time Frame: Baseline and every two weeks for 16 weeks. ]
    The Brief Psychiatric Rating Scale (BPRS) positive symptom items are: conceptual disorganization, hallucinatory behavior, unusual thought content, and suspiciousness. The total score is calculated by adding the scores for each item. Each scale ranges from "1=Not Present" to "7=Very Severe". The minimum score is 4 and the maximum score is 28. A higher score indicates a more severe positive symptom rating. A mixed model for unbalanced repeated measures analysis of covariance (ANCOVA), in which follow-up symptom score = baseline symptom score + treatment + week + treatment x week, and week is treated as a categorical, rather than a continuous measure. The treatment term estimates the average across weeks of the week-specific group differences, and is used as the main test for treatment effects on symptom change.


Secondary Outcome Measures :
  1. Neuropsychological Testing - Overall Composite Z-score [ Time Frame: Baseline and Week 16 ]
    The neuropsychological testing measured attention, executive function/problem solving, motor speed, processing speed/response generation, and verbal, visual, and working memory. The individual test raw scores were converted to z-scores and an overall composite z-score was computed from the average of the individual test z-scores. Z-scores range from -3 standard deviations up to +3 standard deviations. Higher scores indicate better test performance.

  2. Negative Symptom Total Score by Week and Treatment Group [ Time Frame: Baseline and every two weeks for 16 weeks. ]
    The Scale for the Assessment of Negative Symptoms (SANS) total score, minus the global items, inappropriate affect, poverty of content of speech, and attention items, used to measure negative symptoms. SANS total score range = 0-85. Higher scores indicate more severe negative symptoms. A mixed model for unbalanced repeated measures analysis of covariance (ANCOVA), in which follow-up symptom score = baseline symptom score + treatment + week + treatment x week, and week is treated as a categorical, rather than a continuous measure. The treatment term estimates the average across weeks of the week-specific group differences, and is used as the main test for treatment effects on symptom change.



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

Inclusion Criteria:

  • DSM-IV criteria for schizophrenia or schizoaffective disorder
  • Current clozapine treatment
  • Moderate illness severity and inadequate positive symptom response to clozapine treatment
  • 6 month period of clozapine treatment with documented clozapine blood level greater than or equal to 350 ng/ml or clozapine and norclozapine blood level greater than or equal to 450 ng/ml

Exclusion Criteria:

  • Organic brain disorder
  • Mental retardation
  • Medical condition whose pathology or treatment could alter the presentation or treatment of schizophrenia or significantly increase the risk associated with the proposed treatment protocol
  • Pregnancy
  • DSM-IV criteria for current alcohol or substance dependence within the last 6 months or DSM-IV criteria for alcohol or substance abuse within the last month
  • Previously received adjunctive risperidone (at doses greater than or equal to 8 mg/day) with their clozapine treatment for greater than or equal to 6 weeks

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 ClinicalTrials.gov identifier (NCT number): NCT00056498


Locations
United States, Maryland
Maryland Psychiatric Research Center
Catonsville, Maryland, United States, 21228
Sponsors and Collaborators
University of Maryland
National Institute of Mental Health (NIMH)
Ortho-McNeil Janssen Scientific Affairs, LLC
Investigators
Principal Investigator: Robert W Buchanan, MD University of Maryland

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert W. Buchanan, Professor of Psychiatry, University of Maryland
ClinicalTrials.gov Identifier: NCT00056498     History of Changes
Other Study ID Numbers: R01 MH045074 H-21270
R01MH045074 ( U.S. NIH Grant/Contract )
DSIR 83-ATAP
First Posted: March 17, 2003    Key Record Dates
Results First Posted: July 16, 2012
Last Update Posted: February 15, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Risperidone
Clozapine
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
GABA Antagonists
GABA Agents