Best Event Schizophrenia Trial--A Randomized Double-Blind Trial of Aripiprazole and Risperidone in Schizophrenia

Study Overview
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Brief Summary
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This study is being conducted to find a way to predict how individual schizophrenic patients will respond if they are treated with different types of antipsychotic drugs. This could help doctors prescribe the medication that will work best for each individual.

Detailed Description
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The primary objective of the proposed research project is to identify a practical method of predicting differential antipsychotic drug treatment response in patients with schizophrenia. In particular, we will examine differential response to two antipsychotic drugs, aripiprazole and risperidone, that have contrasting pharmacologic activity at D2-type dopamine receptors, i.e., partial agonism vs. antagonism, respectively. A number of candidate predictors will be examined, including neuroimaging parameters (regional neuroanatomical and metabolic variations, fallypride binding to D2-like receptors), neuropsychological testing, clinical features, laboratory measures, and genetic studies. Secondary objectives include: (1) extension of our previous efforts to characterize abnormalities in cortico-striato-thalamic circuits in unmedicated schizophrenics using PET and MR imaging; and, (2) examination of the role of omega-3 fatty acid activity in schizophrenics as a predictor of dopaminergic activity.

Official Title
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A Randomized Double-blind Trial of Aripiprazole and Risperidone in Schizophrenia: An Evaluation of Neuroimaging, Neuropsychological, and Pharmacogenomic Markers of Differential Treatment Response

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Aripiprazole
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will meet DSM-IV diagnostic criteria for schizophreniform disorder, schizophrenia, schizoaffective disorder or (non-affective) psychotic disorder, NOS. Subjects with schizophreniform disorder or psychotic disorder, NOS, will be diagnostically reevaluated (recontacted if no longer involved in the study) after a minimum of six months of psychotic symptoms in order to determine whether diagnostic criteria for schizophrenia or schizoaffective disorder have been met. Subjects will be between 18 and 55 years of age, inclusive. Subjects will be able to fully participate in the informed consent process, or have a legal guardian able to participate in the informed consent process. Present score on at least one PANSS psychosis items (P1, P2, P3, P5 or P6) > 4(moderately severe) and CGI Severity score > 4 (moderate). Female patients of childbearing potential must be using a medically accepted means of contraception Exclusion Criteria: Current active substance use disorder diagnosis or a history of cocaine abuse or dependence; Female patients who are either pregnant or nursing; Known history of mental retardation, seizure disorder, or a clinically significant head injury (prolonged loss of consciousness, neurological sequelae, or demonstrated structural brain injury); Non-English speaking (mastery of English insufficient to participate in study evaluation procedures); Serious, unstable medical illness; Known hypersensitivity to any study medication; Medical contraindication to any element of the study procedure; Current symptoms which present serious risk of danger to self or others; Participation in a clinical trial of an investigational drug within 30 days of study entry; Current severity of psychiatric symptoms contraindicates a delay in initiation of antipsychotic medication treatment until functional imaging studies and neuropsychological testing have been completed; Baseline QTc interval of > 450 msec.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br>Screening and Baseline Procedures followed by Referral to Community Care. Baseline Procedures may be repeated at a later time if appropriate. | |
| Active Comparator: Drug: Aripiprazole<br>Screening and Baseline Procedures followed by 16 weeks of treatment with aripiprazole, followed by repeat of baseline procedures and referral to community care. | Drug: Aripiprazole<br>* Target dose = 15mg by mouth per day for 16 weeks. The dosage will be titrated in accordance with the treating physician's clinical judgment, generally reaching full dosage within one week of initiation. The dosage may be increased as clinically indicated, by the treating physician. Any deviation from these target dosing schedules must be reviewed and approved by the principal investigator, generally prior to the adjustment unless clinical circumstances require more immediate adjustment (in which case the treating physician should consult with the principal investigator as soon as is practically possible).<br>* Other names: Abilify;|
| Active Comparator: Risperidone<br>Screening and Baseline Procedures followed by 16 weeks of treatment with Risperidone,followed by repeat of baseline procedures and referral to community care. | Drug: Risperidone<br>* Target Dose = 2mg by mouth per day for 16 weeks. The dosage will be titrated in accordance with the treating physician's clinical judgment, generally reaching full dosage within one week of initiation. The dosage may be increased as clinically indicated, by the treating physician. Any deviation from these target dosing schedules must be reviewed and approved by the principal investigator, generally prior to the adjustment unless clinical circumstances require more immediate adjustment (in which case the treating physician should consult with the principal investigator as soon as is practically possible).<br>* Other names: Risperdal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre and Post Treatment PET and MRI Imaging |  | At baseline and 16 weeks | 
| QTc Measurement | Information regarding the Outcome Measure being a Primary or Secondary, is unavailable. |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Pretreatment and Posttreatment Psychiatric Rating Scales to Include PANSS and CGI | Study was terminated back in 2009 with limited data available. Randomization is not known. Only 7 subjects completed study. Data for this objective is not available. | 7 visits over 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Antipsychotic drug treatment response, Risperidone, Aripiprazole, Fallypride, Positron emission tomography, Magnetic Resonance Imaging, Dopamine D2 Receptors