Relationship Between Neurotransmitter Receptor Polymorphisms, Plasma Concentrations and Clinical Response to Clozapine

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

This is a study designed to identify genetic polymorphisms (also called allelic variants or genetic markers) that are associated with response to clozapine. This information will be used to enhance the understanding of clozapine response and side effects. DNA from patients will be examined for significant associations between allelic variants in candidate genes in relation to clozapine effects on positive and negative symptoms, global response, quality of life, relapse rates and side effects.

Condition or disease
Schizophrenia

Detailed Description:

Patients age 18-65 with a DSM IV diagnosis of schizophrenia who have a history of nonresponse to conventional atypical antipsychotics and who are to be treated with clozapine by their psychiatrist, will be asked to participate at or near the time clozapine therapy is initiated. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and the Scale for the Assessment of Positive Symptoms (SAPS) will be performed on all subjects at entry into the study, at 3 weeks, 5 weeks, 8 weeks, and at 4 and 6 months. Adverse effects will be monitored with the Simpson-Angus Scale, Barnes Akathisia scale and the AIMS at each of these time points. The Calgary Depression Scale will also be administered at each visit. A complete neurocognitive assessment battery will be completed at entry and at 6 months for those subjects willing to undergo neurocognitive testing. It is anticipated not all subjects will complete neurocognitive testing. A blood or cheek swab sample will be collected at study entry for DNA analysis. Plasma blood levels will be collected at weeks 3, 5, 8 and study completion for measurement of clozapine plasma concentrations. The subject's weight, BMI, smoking status and concomitant medications will be recorded at each visit.

Study Design

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Observational
Actual Enrollment :	76 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Relationship Between Neurotransmitter Receptor Polymorphisms, Plasma Concentrations and Clinical Response to Clozapine
Study Start Date :	October 2001
Actual Primary Completion Date :	December 2015
Actual Study Completion Date :	December 2015

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
A; One group, all subjects with DSM-IV diagnosis of Schizophrenia, age 18-65 who are initiating clozapine therapy.

Outcome Measures

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Primary Outcome Measures :

1. Brief Psychiatric Rating Scale [ Time Frame: entry, 3 wks, 5 wks, 8 wks, 4 mo, 6 mo ]

Secondary Outcome Measures :

1. Scale for the Assessment of Positive Symptoms [ Time Frame: entry, wk 3, wk 5, wk 8, 4 mo, 6 mo ]
2. Scale for the assessment of Negative symptoms [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ]
3. Calgary Depression Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ]
4. Abnormal Involuntary Movement Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ]
5. Barnes Akathisia Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ]

Biospecimen Retention:   Samples With DNA

whole blood, saliva

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Psychiatric clinic, Inpatient Psychiatry unit

Criteria

Inclusion Criteria:

• Diagnosis of schizophrenia
• Beginning clozapine therapy
• age 18-65
• must be willing to participate in interviews and provide a DNA sample

Exclusion Criteria:

• no longer taking clozapine

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242

Sponsors and Collaborators

Delwyn D. Miller

Investigators

Principal Investigator:	Del D Miller, PharmD, M.D.	The University of Iowa

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Delwyn D. Miller, Professor, University of Iowa
ClinicalTrials.gov Identifier:	NCT00581932 History of Changes
Other Study ID Numbers:	199901018
First Posted:	December 28, 2007
Last Update Posted:	May 12, 2017
Last Verified:	May 2017

Keywords provided by Delwyn D. Miller, University of Iowa:

clozapine, schizophrenia

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Clozapine; Neurotransmitter Agents; Serotonin Antagonists; Serotonin Agents; Molecular Mechanisms of Pharmacological Action	Physiological Effects of Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; GABA Antagonists; GABA Agents