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| ID | Type | Description | Link |
|---|---|---|---|
| R01MH045074 | U.S. NIH Grant/Contract | View source | |
| DSIR 83-ATAP |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
| Ortho-McNeil Janssen Scientific Affairs, LLC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active | Active Comparator | Participants assigned to risperidone |
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| Placebo | Placebo Comparator | Participants assigned to placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo capsule daily for 16 weeks |
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| Risperdal |
| Measure | Description | Time Frame |
|---|---|---|
| Positive Symptom Item Scores by Week and Treatment Group | 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. | Baseline and every two weeks for 16 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Neuropsychological Testing - Overall Composite Z-score | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert W Buchanan, MD | University of Maryland, College Park | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maryland Psychiatric Research Center | Catonsville | Maryland | 21228 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20664583 | Derived | Weiner E, Conley RR, Ball MP, Feldman S, Gold JM, Kelly DL, Wonodi I, McMahon RP, Buchanan RW. Adjunctive risperidone for partially responsive people with schizophrenia treated with clozapine. Neuropsychopharmacology. 2010 Oct;35(11):2274-83. doi: 10.1038/npp.2010.101. Epub 2010 Jul 21. |
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86 Participants signed informed consent. 15 were ineligible or excluded. 71 Participants entered the evaluation phase. Two were withdrawn prior to randomization. Four people withdrew after randomization but prior to starting study medications.
Though funding was in place beginning in 2001, recruitment took place from 2003 to 2008. Subjects were recruited from the Maryland Psychiatric Research Center Outpatient Reseach clinic, the Treatment Research Program, and community mental health centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Risperidone | Participants assigned to risperidone |
| FG001 | Placebo | Participants assigned to placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Risperidone | Participants assigned to risperidone |
| BG001 | Placebo | Participants assigned to placebo |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Positive Symptom Item Scores by Week and Treatment Group | 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. | The intent to treat analysis included all participants who received at least one dose of study medication and completed the BPRS rating at the specified week. | Posted | Mean | Standard Deviation | units on a scale | Baseline and every two weeks for 16 weeks. |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Risperidone | Participants assigned to risperidone |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| increased auditory hallucinations | Psychiatric disorders | Systematic Assessment | Participant was hospitalized due to an increase in intensity of auditory hallucinations including commands to harm self and need for hospitalization. Considered to be moderate in severity, and remotely study drug and concomitant drug related. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Robert W. Buchanan, MD | Maryland Psychiatric Research Center | 410-402-7876 | rwbuchanan@mprc.umaryland.edu |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D018967 | Risperidone |
| ID | Term |
|---|---|
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Drug |
Risperdal 4 mg per day for 16 weeks |
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| Baseline and Week 16 |
| Negative Symptom Total Score by Week and Treatment Group | 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. | Baseline and every two weeks for 16 weeks. |
| BG002 |
| Total |
Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Description |
|---|
| OG000 | Risperidone | Participants assigned to risperidone |
| OG001 | Placebo | Participants assigned to placebo |
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| Secondary | Neuropsychological Testing - Overall Composite Z-score | 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. | Two participants completed 9 or fewer of the 13 individual tests in the neurocognitive battery, and were omitted from calculation of the overall composite score | Posted | Mean | Standard Deviation | z-score | Baseline and Week 16 |
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| Secondary | Negative Symptom Total Score by Week and Treatment Group | 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. | The intent to treat analysis included all participants who received at least one dose of study medication and completed the SANS rating at the specified treatment week. | Posted | Mean | Standard Deviation | units on a scale | Baseline and every two weeks for 16 weeks. |
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| 1 |
| 30 |
| 0 |
| 30 |
| EG001 | Placebo | Participants assigned to placebo | 2 | 35 | 0 | 35 |
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| gastrointestinal symptoms | Gastrointestinal disorders | Systematic Assessment | Subject c/o of diarrhea, nausea, and vomiting with a history of constipation and admitted to the hospital. Subject was treated for renal failure secondary to nausea and vomiting. Considered to be severe and possibly drug related. |
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| Panic attack | Psychiatric disorders | Systematic Assessment | Subject reported to the ER c/o racing pulse and thoughts and experiencing a "panic attack". After overnight observation, patient reports symptoms subsided and all labwork was normal. Determined to be severe and remotely study drug related. |
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