Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients

This study is not yet open for participant recruitment.

Verified July 2012 by Tirat Carmel Mental Health Center

Sponsor:

Collaborators:

Technion, Israel Institute of Technology

Ben-Gurion University of the Negev

Beersheva Mental Health Center

Sha’ar Menashe Mental Health Center

HaEmek Medical Center, Israel

The Nazareth Hospital, Israel

Information provided by (Responsible Party):

Anatoly Dr. Kreinin, Tirat Carmel Mental Health Center

ClinicalTrials.gov Identifier:

NCT01663077

First received: July 25, 2012

Last updated: August 8, 2012

Last verified: July 2012

History of Changes

Tracking Information

First Received Date ^ICMJE

July 25, 2012

Last Updated Date

August 8, 2012

Start Date ^ICMJE

October 2012

Estimated Primary Completion Date

May 2013 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Clozapine steady state plasma level [ Time Frame: 3 month ] [ Designated as safety issue: Yes ]

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT01663077 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Polymorphism of CYP1A2, CYP3A4, CYP3A5 and CYP2D6 in clinically stable schizophrenic adult patients [ Time Frame: Once ] [ Designated as safety issue: Yes ]

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients

Official Title ^ICMJE

Clozapine Fixed Dose Steady State Plasma Levels and the Relationship to the Polymorphism of CYP1A2, CYP3A4, CYP3A5 and CYP2D6 in Clinically Stable Schizophrenic Adult Patients

Brief Summary

Approximately 30-60% of all schizophrenia patients who fail to respond to typical antipsychotics may respond to Clozapine. Clozapine has long been considered the "gold standard" within the atypical neuroleptic spectrum, backed by years of clinical experience and research, but uncertainties remain in some aspects of this drug. One such question is the link between dose, blood levels and patient clinical response. The Clozapine therapeutic plasma levels range between 250 - 450 ng/mL creating difficulties in using these results in routine clinical practice. Approximately 30% - 51% of "treatment-resistant schizophrenia" patients do not fully respond to Clozapine, a poorly understood phenomenon. Factors relevant to Clozapine-resistance include co-morbidity, drug misuse, poor adherence, inadequate duration of treatment and inadequate dose/plasma-levels. Pharmacogenetic factors such as different polymorphisms in involved genes may play a role. Pharmacodynamic and genetic data appear important in determining the clinical response to Clozapine. Clozapine-treated patients possessing different 3A4 polymorphisms, may respond differently as compared to other patients having normal 3A4 alleles. Recently, the CYP2D6 has also been involved in this drug metabolic pathway. Population pharmacokinetics of clozapine evaluated with the nonparametric maximum likelihood method. This pharmacogenetic explanation/hypothesis may explain Clozapine- resistance in schizophrenics.

The high variability in plasma levels requires a large study in order to be able to determine correlation between clinical efficacy and plasma levels and genotyping. A preliminary study will enable power analysis and adequate determination of sample size.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 4

Study Design ^ICMJE

Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Schizophrenia

Intervention ^ICMJE

Drug: Clozapine

A fixed dose of Clozapine 300 mg/day (150 mg x 2)for 3 month

Other Name: Leponex

Study Arm (s)

Experimental: Clozapine

Clozapine tablet 150 mg at the day and 150 mg in the evening by mouth per day for 3 month

Intervention: Drug: Clozapine

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

October 2013

Estimated Primary Completion Date

May 2013 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

DSM-IV criteria for schizophrenia (American Psychiatric Association 2000)
All clozapine mono-therapy patients (only 300 mg/day) who respond to treatment and achieved symptomatic remission (45, 46) and were stable for at least 3 month will be included
No change in benzodiazepine medications for the trial period.
Legal ability and willingness to sign an informed consent form for participation in the study.

Exclusion Criteria:

Evidence of serious neurologic or endocrine disorder, for example severe head trauma, seizure disorder, dementia, Cushing's disease, thyroid disorder, mental retardation, alcohol or drug abuse, substance dependence (other than nicotine dependence), or presenting symptoms likely substance- induced, as judged by a study physician.
Unstable medical illness or neurologic illness (seizures, CVA); breast, uterine, or ovarian cancer.
Pregnant women, use of oral contraceptives or other hormonal supplementation such as estrogen. [Female patients will also have a pregnancy test.].

Gender

Both

Ages

18 Years to 65 Years

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Anatoly Kreinin, MD, PhD

+97248559325

ANATOLY.KREININ@PSTIRA.HEALTH.GOV.IL

Location Countries ^ICMJE

Israel

Administrative Information

NCT Number ^ICMJE

NCT01663077

Other Study ID Numbers ^ICMJE

KBK2012, 03/11

Has Data Monitoring Committee

Responsible Party

Anatoly Dr. Kreinin, Tirat Carmel Mental Health Center

Study Sponsor ^ICMJE

Tirat Carmel Mental Health Center

Collaborators ^ICMJE

Technion, Israel Institute of Technology
Ben-Gurion University of the Negev
Beersheva Mental Health Center
Sha’ar Menashe Mental Health Center
HaEmek Medical Center, Israel
The Nazareth Hospital, Israel

Investigators ^ICMJE

Study Director:	Anatoly Kreinin, MD, Phd	Tirat Carmel Mental Health Center
Principal Investigator:	Yedidia Bentur, MD	Rambam Health Care Campus, Haifa
Principal Investigator:	Norberto Krivoy, MD	Rambam Health Care Campus, Haifa
Principal Investigator:	David Rabinowitz, MD	Rambam Health Care Campus, Haifa
Principal Investigator:	Kamal Farhat, MD	The Nazareth Hospital-EMM
Principal Investigator:	Vladimir Lerner, MD, Phd	Beersheva Mental Health Center
Principal Investigator:	Boaz Bloch, MD	Haemek Hospital, Afula
Principal Investigator:	Alexander Grinshpoon, MD, MHA, PhD	Shaar Menashe MHC

Information Provided By

Tirat Carmel Mental Health Center

Verification Date

July 2012

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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