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

This study is currently recruiting participants.
Verified June 2012 by University of Iowa
Sponsor:
Information provided by (Responsible Party):
Delwyn D. Miller, University of Iowa
ClinicalTrials.gov Identifier:
NCT00581932
First received: December 19, 2007
Last updated: June 22, 2012
Last verified: June 2012
  Purpose

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
Schizophrenia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Relationship Between Neurotransmitter Receptor Polymorphisms, Plasma Concentrations and Clinical Response to Clozapine

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Brief Psychiatric Rating Scale [ Time Frame: entry, 3 wks, 5 wks, 8 wks, 4 mo, 6 mo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Scale for the Assessment of Positive Symptoms [ Time Frame: entry, wk 3, wk 5, wk 8, 4 mo, 6 mo ] [ Designated as safety issue: No ]
  • Scale for the assessment of Negative symptoms [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ] [ Designated as safety issue: No ]
  • Calgary Depression Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ] [ Designated as safety issue: No ]
  • Abnormal Involuntary Movement Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ] [ Designated as safety issue: Yes ]
  • Barnes Akathisia Scale [ Time Frame: entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

whole blood, saliva


Estimated Enrollment: 80
Study Start Date: October 2001
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
A
One group, all subjects with DSM-IV diagnosis of Schizophrenia, age 18-65 who are initiating clozapine therapy.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00581932

Contacts
Contact: Timothy L Holman, M.A. 319-335-6769 Timothy-Holman@uiowa.edu
Contact: Jane J Kerr, B.S. 319-353-4955 Jane-Kerr@uiowa.edu

Locations
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Timothy L Holman, M.A.    319-335-6769    Timothy-Holman@uiowa.edu   
Contact: Del D Miller, M.D.    319-353-4506    Del-Miller@uiowa.edu   
Principal Investigator: Del D Miller, PharmD., M.D.         
Sub-Investigator: Timothy L Holman, M.A.         
Sub-Investigator: Jane J Kerr, B.S.         
Sponsors and Collaborators
Delwyn D. Miller
Investigators
Principal Investigator: Del D Miller, PharmD, M.D. The University of Iowa
  More Information

No publications provided

Responsible Party: Delwyn D. Miller, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT00581932     History of Changes
Other Study ID Numbers: 199901018
Study First Received: December 19, 2007
Last Updated: June 22, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Iowa:
clozapine, schizophrenia

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Clozapine
Neurotransmitter Agents
Serotonin Antagonists
Serotonin Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
GABA Antagonists
GABA Agents

ClinicalTrials.gov processed this record on April 14, 2014