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

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

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.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Aripiprazole; Drug: Risperidone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Kettering, Ohio, United States, 45429
      • Wallace Kettering Neuroscience Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Subjects will be between 18 and 55 years of age, inclusive.
3. 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.
4. Present score on at least one PANSS psychosis items (P1, P2, P3, P5 or P6) > 4(moderately severe) and CGI Severity score > 4 (moderate).
5. Female patients of childbearing potential must be using a medically accepted means of contraception

Exclusion Criteria:

1. Current active substance use disorder diagnosis or a history of cocaine abuse or dependence;
2. Female patients who are either pregnant or nursing;
3. Known history of mental retardation, seizure disorder, or a clinically significant head injury (prolonged loss of consciousness, neurological sequelae, or demonstrated structural brain injury);
4. Non-English speaking (mastery of English insufficient to participate in study evaluation procedures);
5. Serious, unstable medical illness;
6. Known hypersensitivity to any study medication;
7. Medical contraindication to any element of the study procedure;
8. Current symptoms which present serious risk of danger to self or others;
9. Participation in a clinical trial of an investigational drug within 30 days of study entry;
10. Current severity of psychiatric symptoms contraindicates a delay in initiation of antipsychotic medication treatment until functional imaging studies and neuropsychological testing have been completed;
11. Baseline QTc interval of > 450 msec.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Standard of Care; 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; 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; 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).; Other Names: Abilify
ACTIVE_COMPARATOR: Risperidone; 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; 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).; Other Names: Risperdal

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kettering Health Network
• Investigators: Principal Investigator: Douglas S Lehrer, MD, Wallace Kettering Neuroscience Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): November 1, 2010

Study Registration Dates

• First Submitted: July 7, 2008
• First Submitted That Met QC Criteria: July 7, 2008
• First Posted (ESTIMATE): July 9, 2008

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2020
• Last Update Submitted That Met QC Criteria: July 10, 2020
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Schizophrenia; Magnetic Resonance Imaging; Aripiprazole; Risperidone; Positron emission tomography; Dopamine D2 Receptors; Antipsychotic drug treatment response; Fallypride
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole; Risperidone
• Other Study ID Numbers: 05-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO