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

• Sponsor: Kettering Health Network (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00712270
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 3
• Duration (Months): 67
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Aripiprazole; Drug: Risperidone	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Double-blind Trial of Aripiprazole and Risperidone in Schizophrenia: An Evaluation of Neuroimaging, Neuropsychological, and Pharmacogenomic Markers of Differential Treatment Response
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Pre and Post Treatment PET and MRI Imaging [At baseline and 16 weeks]

2. QTc Measurement []

   Information regarding the Outcome Measure being a Primary or Secondary, is unavailable.

Secondary Outcome Measures

1. Assessment of Pretreatment and Posttreatment Psychiatric Rating Scales to Include PANSS and CGI [7 visits over 16 weeks]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wallace Kettering Neuroscience Institute	Kettering	Ohio	United States	45429

Sponsors and Collaborators

• Kettering Health Network

Investigators

• Principal Investigator: Douglas S Lehrer, MD, Wallace Kettering Neuroscience Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kettering Health Network
• ClinicalTrials.gov Identifier: NCT00712270
• Other Study ID Numbers: 05-009
• First Posted: Jul 9, 2008
• Last Update Posted: Jul 28, 2020
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Kettering Health Network: Schizophrenia; Antipsychotic drug treatment response; Risperidone; Aripiprazole; Fallypride; Positron emission tomography; Magnetic Resonance Imaging; Dopamine D2 Receptors
• Additional relevant MeSH terms: Schizophrenia; Risperidone; Aripiprazole

Study Results

Participant Flow

Arm/Group Title	Entire Study Population
Arm/Group Description	The study was pre-maturely terminated and limited data is available for reporting, since none of the study team members currently work in the organization, and are not able to be contacted. The randomization coding is not available, therefore, results cannot be reported per-Arm.
Period Title: Overall Study
STARTED	21
COMPLETED	7
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Standard of Care	Drug: Aripiprazole	Risperidone	Total
Arm/Group Description	Screening and Baseline Procedures followed by Referral to Community Care. Baseline Procedures may be repeated at a later time if appropriate.	Screening and Baseline Procedures followed by 16 weeks of treatment with aripiprazole, followed by repeat of baseline procedures and referral to community care. 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).	Screening and Baseline Procedures followed by 16 weeks of treatment with Risperidone,followed by repeat of baseline procedures and referral to community care. 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).	Total of all reporting groups
Overall Participants	0	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Sex: Female, Male () []
Female
Male

Outcome Measures

1. Primary Outcome

Title	Pre and Post Treatment PET and MRI Imaging
Time Frame	At baseline and 16 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Standard of Care	Drug: Aripiprazole	Risperidone
Arm/Group Description	Screening and Baseline Procedures followed by Referral to Community Care. Baseline Procedures may be repeated at a later time if appropriate.	Screening and Baseline Procedures followed by 16 weeks of treatment with aripiprazole, followed by repeat of baseline procedures and referral to community care. 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).	Screening and Baseline Procedures followed by 16 weeks of treatment with Risperidone,followed by repeat of baseline procedures and referral to community care. 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).
Measure Participants	0	0	0

2. Primary Outcome

Title	QTc Measurement
Description	Information regarding the Outcome Measure being a Primary or Secondary, is unavailable.

Outcome Measure Data

Analysis Population Description

Limited data only available for 8 of 21 patients

Arm/Group Title	QTc Pre-treatment for Entire Study Population	QTc Post-treat for Entire Study Population
Arm/Group Description	QTc measurement via ECG prior to treatment initiation.	QTc measurement via ECG after treatment initiation
Measure Participants	8	8
Mean (Full Range) [milliseconds]	381	389

3. Secondary Outcome

Title	Assessment of Pretreatment and Posttreatment Psychiatric Rating Scales to Include PANSS and CGI
Description	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.
Time Frame	7 visits over 16 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Entire Study Population
Arm/Group Description	The study was pre-maturely terminated and limited data is available for reporting, since none of the study team members currently work in the organization, and are not able to be contacted. The randomization coding is not available, therefore, results cannot be reported per-Arm.
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	Study was terminated back in 2009 with limited data available. Randomization is not known. Only 7 subjects completed study. Data for AEs is not available.
Arm/Group Title	Entire Study Population
Arm/Group Description	Study was terminated back in 2009 with limited data available. Randomization is not known. Only 7 subjects completed study.
All Cause Mortality
	Entire Study Population
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Serious Adverse Events
	Entire Study Population
	Affected / at Risk (%)	# Events
Total	0/21 (0%)
Other (Not Including Serious) Adverse Events
	Entire Study Population
	Affected / at Risk (%)	# Events
Total	14/21 (66.7%)
Blood and lymphatic system disorders
Decreased Hemoglobin and Hematocrit	1/21 (4.8%)
Cardiac disorders
Lightheadedness	7/21 (33.3%)	7
Gastrointestinal disorders
Cecal polyps	1/21 (4.8%)
Constipation	4/21 (19%)	4
Decreased appetite	1/21 (4.8%)
Emesis	1/21 (4.8%)
Increased appetite	1/21 (4.8%)
Nausea	1/21 (4.8%)	2
GI distress (indigestion and cramping)	1/21 (4.8%)
GERD (increased symptoms)	1/21 (4.8%)
General disorders
Dry mouth	8/21 (38.1%)
Sialorrhea	3/21 (14.3%)
Fever	1/21 (4.8%)
Claustrophobia	1/21 (4.8%)	4
Musculoskeletal and connective tissue disorders
Leg cramps	1/21 (4.8%)
Shoulder pain	1/21 (4.8%)
Leg pain	1/21 (4.8%)
Tooth extraction	1/21 (4.8%)
Weight gain	1/21 (4.8%)
Weakness	1/21 (4.8%)
Nervous system disorders
Daytime sleepiness	7/21 (33.3%)	7
Akinesia	4/21 (19%)
Insomnia	6/21 (28.6%)
Headache	2/21 (9.5%)
Akathisia	1/21 (4.8%)	3
Renal and urinary disorders
Increased urination	1/21 (4.8%)
Urinalysis abnormalities	1/21 (4.8%)
Urinary Tract Infection	1/21 (4.8%)
Reproductive system and breast disorders
Decreased sexual arousal	1/21 (4.8%)
Elevated serum HCG	1/21 (4.8%)
Post-procedure vaginal bleed	1/21 (4.8%)
Delayed orgasm	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Tonsilitis	1/21 (4.8%)
Upper respiratory infection	2/21 (9.5%)
Sinus congestion	2/21 (9.5%)
Common cold	1/21 (4.8%)
Skin and subcutaneous tissue disorders
Rash	1/21 (4.8%)
Increased sweating	1/21 (4.8%)

Limitations/Caveats

Study was terminated back in 2009 with limited data available. Randomization is not known. Only 7 subjects completed study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.