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

July 25, 2012
August 8, 2012
October 2012
May 2013   (final data collection date for primary outcome measure)
Clozapine steady state plasma level [ Time Frame: 3 month ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01663077 on ClinicalTrials.gov Archive Site
Polymorphism of CYP1A2, CYP3A4, CYP3A5 and CYP2D6 in clinically stable schizophrenic adult patients [ Time Frame: Once ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients
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

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.

Not Provided
Interventional
Phase 4
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Schizophrenia
Drug: Clozapine
A fixed dose of Clozapine 300 mg/day (150 mg x 2)for 3 month
Other Name: Leponex
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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
20
October 2013
May 2013   (final data collection date for primary outcome measure)

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.].
Both
18 Years to 65 Years
No
Contact: Anatoly Kreinin, MD, PhD +97248559325 ANATOLY.KREININ@PSTIRA.HEALTH.GOV.IL
Israel
 
NCT01663077
KBK2012, 03/11
No
Anatoly Dr. Kreinin, Tirat Carmel Mental Health Center
Tirat Carmel Mental Health Center
  • 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
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
Tirat Carmel Mental Health Center
July 2012

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