Ignite Creation Date:
2024-05-05 @ 12:02 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00216281
Status:
TERMINATED
Last Update Posted:
2013-03-26
First Post:
2005-09-19
Brief Title:
Efficacy and Safety Study of Clozapine Augmented by Atomoxetine Versus Clozapine Augmented by Placebo in Patients With Chronic Resistant Schizophrenia
Sponsor:
Indiana University School of Medicine
Organization:
Indiana University
Study Overview
Official Title:
Correlation of Phenotype Genotype and Clinical EfficacyToxicity of Clozapine Augmented by Atomoxetine for Treatment Refractory Schizophrenia CAPG Study
Status:
TERMINATED
Status Verified Date:
2013-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a randomized placebo-controlled study to assess the efficacy and safety of ATX augmentation of CLZ as a treatment for the cognitive symptoms of schizophrenia A total sample size of 126 subjects diagnosed with schizophrenia and being treated with the antipsychotic clozapine will undergo genotyping These subjects will have an initial assessment at four weeks and regular follow-up assessments for a total period of 52 weeks These subjects will be randomized to continued treatment with CLZ and augmentation with ATX or Placebo
Detailed Description:
The purpose of this study is to scientifically explore the potential of pharmacogenetic applications as a means of predicting the clinical efficacy and safety of treatment with clozapine and atomoxetine in a treatment resistant schizophrenic population
The principle enzyme involved in the metabolism of clozapine is CYP1A2 with minor contributions from CYP2D6 However all the subjects will be on a stable dose of clozapine and will continue on the same dosage throughout the study On the other hand half the number of subjects will be randomized to augmentation with atomoxetine and since atomoxetine is predominantly metabolized by CYP2D6 with contributions from CYP2C19 we will focus on genetic variations for CYP2D6 and CYP2C19
The goal of this study is to associate atomoxetine and metabolite drug concentrations with clinical efficacy and the development of any clinical adverse drug reactions and to determine whether clinical outcome efficacy and ADRs experienced following drug ingestion are more likely to be seen in patients who manifest CYP2D6 andor CYP2C19 polymorphisms Other indications for pharmacogenetics in patient care relevance of therapeutic drug monitoring augmentation strategies and dosage guidelines may be generated from the experience and results of this study
Primary Objectives
1 To compare the effects of the combination of CLZATX on cognitive function in patients with schizophrenia as measured by change in a Composite Cognitive index derived from a battery composed of standardized cognitive tests the Brief Assessment of Cognition in Schizophrenia
2 A total sample of 126 subjects diagnosed with schizophrenia and being treated with the antipsychotic clozapine will be recruited to participate in the study All 126 subjects will undergo genetic testing after obtaining informed consent for 31 known mutations in CYP2D6 including gene duplication and deletion as well as two mutations in CYP2C19
Secondary Objectives
1 Determine the concentration of atomoxetine and its two prominent metabolites 4-hydroxyatomoxetine and N-desmethylatomoxetine at the end of week one and four weeks after initiating therapy by LCMSMS analysis
2 Obtain weekly complete blood counts and CLZ levels on screening at the end of week one and week four
3 Clinically evaluate patients and document any adverse drug reactions that occur after starting treatment with atomoxetine
4 To examine the effects of the combination of CLZATX on psychopathology as measured by the Positive and Negative Syndrome Scale PANSS scores PANSS Total PANSS Positive PANSS Negative the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impressions-Improvement Scale
5 To examine the effects of the combination of CLZATX on measures of social cognition Penn Emotional Recognition and Facial Memory Tests
6 To compare the effects of the combination of CLZATX on weight change from baseline
7 To examine the effects of the combination of CLZATX on daily functioning as measured by the NOSIE
8 To examine the effects of the combination of CLZATX on extrapyramidal signs and motor symptoms as measured by the Barnes Akathesia Rating Scale BARS the Abnormal Involuntary Movement Scale AIMS and the Simpson-Angus Scale SAS
9 To evaluate the safety of the combination of CLZATX as measured by treatment-emergent adverse events and changes in vital signs clinical laboratory analytes and electrocardiogram
The principle enzyme involved in the metabolism of clozapine is CYP1A2 with minor contributions from CYP2D6 However all the subjects will be on a stable dose of clozapine and will continue on the same dosage throughout the study On the other hand half the number of subjects will be randomized to augmentation with atomoxetine and since atomoxetine is predominantly metabolized by CYP2D6 with contributions from CYP2C19 we will focus on genetic variations for CYP2D6 and CYP2C19
The goal of this study is to associate atomoxetine and metabolite drug concentrations with clinical efficacy and the development of any clinical adverse drug reactions and to determine whether clinical outcome efficacy and ADRs experienced following drug ingestion are more likely to be seen in patients who manifest CYP2D6 andor CYP2C19 polymorphisms Other indications for pharmacogenetics in patient care relevance of therapeutic drug monitoring augmentation strategies and dosage guidelines may be generated from the experience and results of this study
Primary Objectives
1 To compare the effects of the combination of CLZATX on cognitive function in patients with schizophrenia as measured by change in a Composite Cognitive index derived from a battery composed of standardized cognitive tests the Brief Assessment of Cognition in Schizophrenia
2 A total sample of 126 subjects diagnosed with schizophrenia and being treated with the antipsychotic clozapine will be recruited to participate in the study All 126 subjects will undergo genetic testing after obtaining informed consent for 31 known mutations in CYP2D6 including gene duplication and deletion as well as two mutations in CYP2C19
Secondary Objectives
1 Determine the concentration of atomoxetine and its two prominent metabolites 4-hydroxyatomoxetine and N-desmethylatomoxetine at the end of week one and four weeks after initiating therapy by LCMSMS analysis
2 Obtain weekly complete blood counts and CLZ levels on screening at the end of week one and week four
3 Clinically evaluate patients and document any adverse drug reactions that occur after starting treatment with atomoxetine
4 To examine the effects of the combination of CLZATX on psychopathology as measured by the Positive and Negative Syndrome Scale PANSS scores PANSS Total PANSS Positive PANSS Negative the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impressions-Improvement Scale
5 To examine the effects of the combination of CLZATX on measures of social cognition Penn Emotional Recognition and Facial Memory Tests
6 To compare the effects of the combination of CLZATX on weight change from baseline
7 To examine the effects of the combination of CLZATX on daily functioning as measured by the NOSIE
8 To examine the effects of the combination of CLZATX on extrapyramidal signs and motor symptoms as measured by the Barnes Akathesia Rating Scale BARS the Abnormal Involuntary Movement Scale AIMS and the Simpson-Angus Scale SAS
9 To evaluate the safety of the combination of CLZATX as measured by treatment-emergent adverse events and changes in vital signs clinical laboratory analytes and electrocardiogram
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None