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Cognitive Improvement With Aripiprazole (Abilify) in Patients With Schizophrenia (BMS)

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
aripiprazole
Sponsored by
Louisiana State University Health Sciences Center Shreveport
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring Cognition, Schizophrenia, Schizoaffective disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Patients (n=10): All patients included in the study will have a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder. Outpatients with schizophrenia (DSM-IV 295.00, 295.10, 295.30, 295.60, 295.90) or schizoaffective disorder (DSM-IV 295.70) will be the primary source of subjects for this project, although inpatients that are being discharged will also be acceptable. All patients will be followed longitudinally. Patients who are from 18-65 years of age will be accepted. Patients will be screened for medical and psychiatric diagnoses. At the time of examination and testing, patients must be stable and taking either olanzapine 10 mg per day for at least two weeks, or at least 2 mg of risperidone per day for at least two weeks, or on risperidone Consta injections (at least 25 mg every two weeks) and not taking an anticholinergic medication for at least one week. While recruiting stable patients for this study, this does not necessarily mean free of side effects or free of symptoms of schizophrenia or schizoaffective disorder. Patients that express a desire to switch to aripiprazole may be having side effects, or may be worried that increasing the dose of their current medication may cause side effects. Controls (n=10): The normal control group will provide images of normal response on the behavioral and functional measures, as well as control for the scan-rescan (learning, novelty) effects. They will be matched for age, sex, handedness, and level of education with the patients. They will be screened for medical and psychiatric diagnoses. Exclusion Criteria: Patients: Any comorbid major psychiatric diagnoses (major depressive disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, any disorder with psychosis other than those used as inclusion criteria, bipolar disorder). Any significant or unstable medical disorder (including unstable or uncontrolled diabetes; long term, severe, or uncontrolled hypertension; or any neurological disorder). Clinical judgment will be used on a case-by-case basis. Special care will be taken in examining patients for metabolic disturbances such as hyperglycemia or hyperlipidemia, due to the increased risk of these problems related to the use of antipsychotics. Subjects with clinically unstable and markedly abnormal metabolic profiles will be excluded. Active alcohol or substance dependence. Significant alcohol or substance abuse in the past six weeks or alcohol or substance dependence in the past year (as defined by DSM-IV). Unable to speak, read and understand English, or if the study doctor thinks that the patient cannot follow the study procedures. Inability to understand the purpose of the study and give consent. Subject is hearing impaired. Subject is left-handed. Significant abnormalities on physical/neurological examination not consistent with an inclusive diagnosis. Current treatment with a classical antipsychotic medication. Current treatment with an anticholinergic medication. History of adverse response or previous lack of response to aripiprazole. Pregnant or lactating women. Women of childbearing potential not using medically accepted means of contraception (e.g., intrauterine device [IUD], birth control pills, barrier devices, implanted hormones). Handedness will be tracked, and left-handed patients will be excluded due to the small sample size and the variance this will add to cognitive testing. Controls: Current treatment with any psychotropic or anticholinergic medication. Any major psychiatric diagnoses (major depressive disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, any disorder with psychosis, bipolar disorder, attention-deficit/hyperactivity, learning or developmental disorder). Any significant medical disorder (including unstable or uncontrolled diabetes; long term, severe, or uncontrolled hypertension; or any neurological disorder). Clinical judgment will be used on a case-by-case basis. Any active alcohol or substance dependence in the past six weeks. Significant alcohol or substance abuse in the past six weeks, or alcohol or substance dependence in the past year (as defined by DSM-IV). Inability to understand the purpose of the study and give consent. Significant abnormalities on physical/neurological examination. Subject is hearing impaired. Subject is left-handed. Pregnant or lactating women. Women of childbearing potential not using medically accepted means of contraception (e.g., IUD, birth control pills, barrier devices, implanted hormones). Dropout criteria: subjects that begin the study and are not able to finish the study will be tracked. Ongoing criteria for termination from the study will include: Adverse events that are intolerable to the patient that prevent continued involvement in the study. New onset medical disorder of such significance as to prohibit further involvement. New onset major psychiatric disorder. Initiation or recurrence of alcohol or substance abuse/dependence. Subject withdraws consent for any reason.

Sites / Locations

  • Psychopharmacology Research Clinic

Outcomes

Primary Outcome Measures

fMRI
SAM-BFT + cognitive tests

Secondary Outcome Measures

Full Information

First Posted
September 13, 2005
Last Updated
September 2, 2011
Sponsor
Louisiana State University Health Sciences Center Shreveport
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00211302
Brief Title
Cognitive Improvement With Aripiprazole (Abilify) in Patients With Schizophrenia (BMS)
Official Title
Cognitive Improvement With Aripiprazole (Abilify) in Patients With Schizophrenia. (BMS)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2011
Overall Recruitment Status
Terminated
Why Stopped
Enrollment too difficult
Study Start Date
August 2003 (undefined)
Primary Completion Date
February 2006 (Actual)
Study Completion Date
February 2006 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Louisiana State University Health Sciences Center Shreveport
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Evaluation of cognitive ability in patients with schizophrenia or schizoaffective disorder both before and after a switch from risperidone to aripiprazole may reveal some of the cognitive changes that correlate with the improved response, better side effect profile, and effects on other components of the negative symptom array. Further, examination of brain functional activity using functional magnetic resonance imaging (fMRI) during a verbal learning task, as well as behavioral performance and associated electroencephalographic (EEG) data of episodic memory, working memory and intermediate term verbal memory collected with the Sustained Attention and Memory Brain Function Test (SAM-BFT), may also provide data showing the neural correlates of these changes in cognition.
Detailed Description
Long-range goal is to understand how the schizophrenic brain is abnormal, as well as how the function of the brain changes in response to antipsychotic medication, to better understand and effectively treat disorders with these drugs. This information can be used in other disorder as well, as there are many psychiatric disorders that are targeted by the newer atypical antipsychotics. The objective of this application, which is the next step in pursuit of the long-range goal, is to compare response on a series of cognitive tests (verbal learning, working memory, and attention) and changes in brain activity in a group of patients with schizophrenia or schizoaffective disorder who are taking risperidone, olanzapine, or risperidone Consta injections and who switch to aripiprazole, and in a group of normal control subjects evaluated twice to control for learning effects. The central hypothesis of this application is that patients with schizophrenia or schizoaffective disorder that are taking aripiprazole will have improvements in cognition consistent with the medication's efficacy. We expect that changes in brain activity (from fMRI and EEG) will be correlated with this improvement, as determined by performance on cognitive tests. Further, changes in regional connectivity of affected brain regions will reflect these specific cognitive changes related to aripiprazole. The rationale for this proposed study is that, once we have a better understanding of which drugs improve cognition and what brain regions respond differently to aripiprazole and risperidone, olanzapine, or risperidone Consta, we will have a better understanding of the functional differences tied to the differential actions of the drugs. This is important, because we really don't understand how these medications affect cognition.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
Cognition, Schizophrenia, Schizoaffective disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
aripiprazole
Other Intervention Name(s)
Abilify
Intervention Description
10-15 mg/day; if needed, dosage may be increased to 30 mg/day after week 2; maintenance 15 mg/day; periodically reassessed
Primary Outcome Measure Information:
Title
fMRI
Time Frame
at Week 2 and Week 16
Title
SAM-BFT + cognitive tests
Time Frame
at Week 3 and Week 16

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Patients (n=10): All patients included in the study will have a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder. Outpatients with schizophrenia (DSM-IV 295.00, 295.10, 295.30, 295.60, 295.90) or schizoaffective disorder (DSM-IV 295.70) will be the primary source of subjects for this project, although inpatients that are being discharged will also be acceptable. All patients will be followed longitudinally. Patients who are from 18-65 years of age will be accepted. Patients will be screened for medical and psychiatric diagnoses. At the time of examination and testing, patients must be stable and taking either olanzapine 10 mg per day for at least two weeks, or at least 2 mg of risperidone per day for at least two weeks, or on risperidone Consta injections (at least 25 mg every two weeks) and not taking an anticholinergic medication for at least one week. While recruiting stable patients for this study, this does not necessarily mean free of side effects or free of symptoms of schizophrenia or schizoaffective disorder. Patients that express a desire to switch to aripiprazole may be having side effects, or may be worried that increasing the dose of their current medication may cause side effects. Controls (n=10): The normal control group will provide images of normal response on the behavioral and functional measures, as well as control for the scan-rescan (learning, novelty) effects. They will be matched for age, sex, handedness, and level of education with the patients. They will be screened for medical and psychiatric diagnoses. Exclusion Criteria: Patients: Any comorbid major psychiatric diagnoses (major depressive disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, any disorder with psychosis other than those used as inclusion criteria, bipolar disorder). Any significant or unstable medical disorder (including unstable or uncontrolled diabetes; long term, severe, or uncontrolled hypertension; or any neurological disorder). Clinical judgment will be used on a case-by-case basis. Special care will be taken in examining patients for metabolic disturbances such as hyperglycemia or hyperlipidemia, due to the increased risk of these problems related to the use of antipsychotics. Subjects with clinically unstable and markedly abnormal metabolic profiles will be excluded. Active alcohol or substance dependence. Significant alcohol or substance abuse in the past six weeks or alcohol or substance dependence in the past year (as defined by DSM-IV). Unable to speak, read and understand English, or if the study doctor thinks that the patient cannot follow the study procedures. Inability to understand the purpose of the study and give consent. Subject is hearing impaired. Subject is left-handed. Significant abnormalities on physical/neurological examination not consistent with an inclusive diagnosis. Current treatment with a classical antipsychotic medication. Current treatment with an anticholinergic medication. History of adverse response or previous lack of response to aripiprazole. Pregnant or lactating women. Women of childbearing potential not using medically accepted means of contraception (e.g., intrauterine device [IUD], birth control pills, barrier devices, implanted hormones). Handedness will be tracked, and left-handed patients will be excluded due to the small sample size and the variance this will add to cognitive testing. Controls: Current treatment with any psychotropic or anticholinergic medication. Any major psychiatric diagnoses (major depressive disorder, obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, any disorder with psychosis, bipolar disorder, attention-deficit/hyperactivity, learning or developmental disorder). Any significant medical disorder (including unstable or uncontrolled diabetes; long term, severe, or uncontrolled hypertension; or any neurological disorder). Clinical judgment will be used on a case-by-case basis. Any active alcohol or substance dependence in the past six weeks. Significant alcohol or substance abuse in the past six weeks, or alcohol or substance dependence in the past year (as defined by DSM-IV). Inability to understand the purpose of the study and give consent. Significant abnormalities on physical/neurological examination. Subject is hearing impaired. Subject is left-handed. Pregnant or lactating women. Women of childbearing potential not using medically accepted means of contraception (e.g., IUD, birth control pills, barrier devices, implanted hormones). Dropout criteria: subjects that begin the study and are not able to finish the study will be tracked. Ongoing criteria for termination from the study will include: Adverse events that are intolerable to the patient that prevent continued involvement in the study. New onset medical disorder of such significance as to prohibit further involvement. New onset major psychiatric disorder. Initiation or recurrence of alcohol or substance abuse/dependence. Subject withdraws consent for any reason.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James C Patterson, MD, PhD
Organizational Affiliation
LSU Health Sciences Center-Shreveport/Department of Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
Psychopharmacology Research Clinic
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States

12. IPD Sharing Statement

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Cognitive Improvement With Aripiprazole (Abilify) in Patients With Schizophrenia (BMS)

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