Comparison of Aripiprazole and Risperidone for the Treatment of People With First-Episode Psychosis - Full Text View

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:	NCT00320671

Purpose

This 52 week long study evaluates the effectiveness of aripiprazole versus risperidone in treating people with first-episode schizophrenia. Patients who do not improve with these medications receive clozapine as their third medication trial.

Condition	Intervention	Phase
Schizophrenia	Drug: Aripiprazole Drug: Risperidone Drug: Clozapine	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Preventing Morbidity in First Episode Schizophrenia, Part II

Resource links provided by NLM:

MedlinePlus related topics: Psychotic Disorders Schizophrenia

Drug Information available for: Risperidone Aripiprazole Clozapine

U.S. FDA Resources

Further study details as provided by National Institute of Mental Health (NIMH):

Primary Outcome Measures:

Treatment response [ Time Frame: Measured at Weeks 12, 16, 32, 52 ] [ Designated as safety issue: No ]
Patterns of change in weight and body mass index (BMI) [ Time Frame: Measured at Weeks 12, 16, 32, 52 ] [ Designated as safety issue: No ]
Incidence rates of metabolic syndrome and new-onset diabetes [ Time Frame: Measured at Weeks 12, 16, 32, 52 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Negative symptoms [ Time Frame: Measured at Weeks 12, 16, 32, 52 ] [ Designated as safety issue: No ]
Cognition [ Time Frame: Measured at Weeks 12, 52 ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: Measured at Week 12 ] [ Designated as safety issue: No ]
Adverse events other than metabolic [ Time Frame: Measured at Weeks 12, 16, 32, 52 ] [ Designated as safety issue: No ]
Substance use [ Time Frame: Measured at Weeks 12, 16, 32, 52 ] [ Designated as safety issue: No ]

Estimated Enrollment:	242
Study Start Date:	December 2005
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will take aripiprazole	Drug: Aripiprazole The dosage for aripiprazole will be 5 mg to 30 mg per day in capsule form. The dose of aripiprazole will be based on the participant's clinical improvement and side effects, which will be evaluated weekly for the first 4 weeks and then every 2 weeks until the 12th week and then monthly until study end.
2: Experimental Participants will take risperidone	Drug: Risperidone The dosage for risperidone will be 1 mg to 6 mg per day in capsule form. The dose of risperidone will be based on the participant's clinical improvement and side effects, which will be evaluated weekly for the first 4 weeks, then every 2 weeks until the 12th week, and then monthly until the study end.
3: Experimental Participants will take Clozapine	Drug: Clozapine The dosage for clozapine will be 12.5 mg per day on day 1; 25 mg per day on days 2 and 3; 50 mg per day on days 4 and 5; 75 mg per day on days 6 and 7; 100 mg per day on days 8 and 9, and increments of 50 mg per day every 2 days until treatment response, dose-related side effects, or a maximum dose of 600 mg/day. Safety monitoring for clozapine-treated subjects will follow the established procedures for multi-episode patients (e.g. weekly CBC monitoring). Subjects who participate in the clozapine trial will be seen for research assessments weekly for 4 weeks, then every two weeks until study end

Detailed Description:

Schizophrenia is a severely disabling brain disorder. People with schizophrenia often experience hallucinations, delusions, thought disorders, and movement disorders. Medications are available to alleviate the symptoms of schizophrenia, but many cause undesirable side effects. For example, two early second generation antipsychotics, olanzapine and risperidone, have been shown to be effective in treating schizophrenia symptoms, but cause rapid, substantial weight gain. There is a lower risk of such side effects with newer second generation antipsychotics, such as aripiprazole. Little is known, however, about the effectiveness of these newer medications in treating people with first-episode schizophrenia. This study will evaluate the effectiveness of aripiprazole versus risperidone for the treatment of first-episode schizophrenia.

Participants in this double-blind study will be randomly assigned to receive either aripiprazole or risperidone for 12 weeks. Subjects who do not meet response criteria will be continued on their initial blinded antipsychotic for an additional 4 weeks for a total length of 16 weeks of treatment. Subjects who meet response criteria by week 16 will continue on their successful blinded medication for their remaining time in study. Patients who do not respond will be treated with the other medication (aripiprazole or risperidone) that they did not receive during the first 16 weeks of the study. The second antipsychotic trial will last 16 weeks. Patients who respond during the switch phase will be continued on their successful medication during their remaining time in the study. Patients who do not respond to the second medication trial will then be treated with open-label clozapine for 20 weeks. Safety monitoring for clozapine-treated subjects will follow the established procedures for multi-episode patients (e.g . weekly CBC monitoring). The total length of patient participation is 52 weeks.

During the longitudinal follow-up phase, subjects may be prescribed open-label sodium valproate for manic symptoms and open-label sertraline for symptoms of depression or anxiety empirically responsive to SSRI treatment. Additionally, all participants will take part in a Healthy Lifestyles program aimed at preventing weight gain. The Healthy Lifestyles program will provide psycho-education, supportive psychotherapy, and medication adherence counseling. At each visit, treatment and metabolic outcomes will be assessed. Participants will meet with both a psychiatrist, who will evaluate progress and medication dosage, and a social worker, who will administer the Healthy Lifestyles Program. Upon completion of the study, participants will receive follow-up care from clinical staff members who were not part of the research team.

For information on a related study, please follow this link:

http://clinicaltrials.gov/show/NCT00000374

Eligibility

Ages Eligible for Study:	15 Years to 40 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Current DSM-IV diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or similar psychotic disorder not otherwise specified, as assessed using the Structured Clinical Interview for Axis I DSM-IV Disorders (SCID-I/P)
History of previous antipsychotic medication treatment for a duration of 2 weeks or less
Current positive symptoms rated 4 (moderate) or more on one or more of the following Brief Psychiatric Rating Scale (BPRS-A) items: conceptual disorganization; grandiosity; hallucinatory behavior; or unusual thought content
Agrees to use an effective form of contraception

Exclusion Criteria:

Any serious neurological or endocrine disorder, or any medical condition or treatment known to affect the brain
Any current medical condition that requires treatment with a medication with psychotropic effects
At significant risk for suicidal or homicidal behavior
Cognitive or language limitations, or any other factor that would interfere with a participant's ability to provide informed consent or safely participate in study procedures
Diagnosis of diabetes, defined as a fasting plasma glucose level of at least 126 mg/dL, or metabolic syndrome, defined as three or more of the following: high blood pressure (greater than 135/85 mmHg); truncal obesity (having a waist circumference greater than 40 inches for men and greater than 35 inches for women); elevated fasting glucose (greater than 110 mg/dL); low HDL-cholesterol (less than 40 mg/dL for men and less than 50 mg/dL for women); or elevated triglycerides (defined as greater than 150 mg/dL)
Requires treatment with an antidepressant or mood stabilizing medication
Meets DSM-IV criteria for a current substance-induced psychotic disorder, a psychotic disorder due to a general medical condition, delusional disorder, brief psychotic disorder, shared psychotic disorder, or a mood disorder (major depression or bipolar) with psychotic features
Any medical conditions that would make treatment with risperidone or aripiprazole medically inadvisable

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00320671

Contacts

Contact: Joanne McCormack, LMSW	718-470-8446	JmcCorma@lij.edu
Contact: Delbert Robinson, MD	718-470-8195	robinson@lij.edu

Locations

United States, New Jersey
East Orange General Hospital	Recruiting
East Orange, New Jersey, United States, 07018
Contact: Chitra Malur, MD 973-266-2930 Malurc@evh.org
United States, New York
The Zucker Hillside Hospital	Recruiting
Glen Oaks, New York, United States, 11004
Contact: Joanne McCormack, MSW 718-470-8446 JmcCorma@lij.edu
Contact: Delbert Robinson, MD 718-470-8195 robinson@lij.edu
Principal Investigator: Delbert Robinson, MD
Sub-Investigator: Serge Sevy, MD
Jamaica Hospital	Recruiting
Jamaica, New York, United States, 11418
Contact: Tom Pawelzik, L Psic 718-206-7318 tpawelzi@jhmc.org
Principal Investigator: Seeth Vivek, MD
Bronx-Lebanon Hospital Center	Recruiting
Bronx, New York, United States, 10456
Contact: Raman Patel, MD 718-901-8883 rpatel@bronxleb.org
Principal Investigator: Raman Patel, MD
Brookdale University Hospital and Medical Center	Recruiting
Brooklyn, New York, United States, 11212
Contact: Daphne Boyd 718-240-5811 dboyd@brookdale.edu
Principal Investigator: Manoj Shah, MD
North Shore University Hospital	Recruiting
Manhasset, New York, United States, 11030
Contact: Delbert Robinson, MD 718-470-8195 robinson@lij.edu
Principal Investigator: Delbert Robinson, MD
United States, Texas
University of Texas Health Science Center at San Antonio	Recruiting
San Antonio, Texas, United States, 78229
Contact: Rochelle Javors 210-562-5402 javorsr@uthscsa.edu
Principal Investigator: Alexander Miller, MD

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

Investigators

Principal Investigator:

Delbert Robinson, MD

The North Shore-Long Island Jewish Health System

More Information

No publications provided

Responsible Party:	The Zucker Hillside Hospital ( Delbert Robinson, MD / Principal Investigator )
Study ID Numbers:	R01 MH060004-02, DSIR 83-ATAP
Study First Received:	May 1, 2006
Last Updated:	September 25, 2009
ClinicalTrials.gov Identifier:	NCT00320671 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Mental Health (NIMH):

First-episode
Schizoaffective Disorder
Schizophreniform Disorder
Psychotic Disorder NOS

Aripiprazole
Clozapine
Risperidone

Additional relevant MeSH terms:

Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Risperidone
Central Nervous System Depressants
Dopamine Antagonists
Antipsychotic Agents
Pharmacologic Actions
Schizophrenia

GABA Antagonists
Serotonin Antagonists
Serotonin Agents
Mental Disorders
Therapeutic Uses
Clozapine
GABA Agents
Dopamine Agents
Aripiprazole
Central Nervous System Agents
Schizophrenia and Disorders with Psychotic Features

ClinicalTrials.gov processed this record on November 30, 2009