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

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 76

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Psychiatric clinic, Inpatient Psychiatry unit

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Brief Psychiatric Rating Scale	entry, 3 wks, 5 wks, 8 wks, 4 mo, 6 mo

Secondary Outcome Measures

Outcome Measure	Time Frame
Scale for the Assessment of Positive Symptoms	entry, wk 3, wk 5, wk 8, 4 mo, 6 mo
Scale for the assessment of Negative symptoms	entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo
Calgary Depression Scale	entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo
Abnormal Involuntary Movement Scale	entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo
Barnes Akathisia Scale	entry, 3 wk, 5 wk, 8 wk, 4 mo, 6 mo

Collaborators and Investigators

• Sponsor: Delwyn D. Miller
• Investigators: Principal Investigator: Del D Miller, PharmD, M.D., University of Iowa

Study record dates

Study Major Dates

• Study Start: October 1, 2001
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: December 19, 2007
• First Posted (ESTIMATE): December 28, 2007

Study Record Updates

• Last Update Posted (ACTUAL): May 12, 2017
• Last Update Submitted That Met QC Criteria: May 11, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: clozapine, schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: 199901018