Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients
Primary Purpose
Schizophrenia
Status
Completed
Phase
Phase 4
Locations
Israel
Study Type
Interventional
Intervention
Clozapine
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Clozapine, Schizophrenia, Remissia, polymorphism
Eligibility Criteria
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.].
Sites / Locations
- Tirat Carmel Mental Health Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Clozapine
Arm Description
Clozapine tablet 150 mg at the day and 150 mg in the evening by mouth per day for 3 month
Outcomes
Primary Outcome Measures
Clozapine steady state plasma level
Secondary Outcome Measures
Polymorphism of CYP1A2, CYP3A4, CYP3A5 and CYP2D6 in clinically stable schizophrenic adult patients
Full Information
NCT ID
NCT01663077
First Posted
July 25, 2012
Last Updated
October 11, 2017
Sponsor
Tirat Carmel Mental Health Center
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
1. Study Identification
Unique Protocol Identification Number
NCT01663077
Brief Title
Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tirat Carmel Mental Health Center
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
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia
Keywords
Clozapine, Schizophrenia, Remissia, polymorphism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Clozapine
Arm Type
Experimental
Arm Description
Clozapine tablet 150 mg at the day and 150 mg in the evening by mouth per day for 3 month
Intervention Type
Drug
Intervention Name(s)
Clozapine
Other Intervention Name(s)
Leponex
Intervention Description
A fixed dose of Clozapine 300 mg/day (150 mg x 2)for 3 month
Primary Outcome Measure Information:
Title
Clozapine steady state plasma level
Time Frame
3 month
Secondary Outcome Measure Information:
Title
Polymorphism of CYP1A2, CYP3A4, CYP3A5 and CYP2D6 in clinically stable schizophrenic adult patients
Time Frame
Once
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.].
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anatoly Kreinin, MD, Phd
Organizational Affiliation
Tirat Carmel Mental Health Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Yedidia Bentur, MD
Organizational Affiliation
Rambam Health Care Campus, Haifa
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Norberto Krivoy, MD
Organizational Affiliation
Rambam Health Care Campus, Haifa
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Rabinowitz, MD
Organizational Affiliation
Rambam Health Care Campus, Haifa
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kamal Farhat, MD
Organizational Affiliation
The Nazareth Hospital-EMM
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vladimir Lerner, MD, Phd
Organizational Affiliation
Beersheva Mental Health Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Boaz Bloch, MD
Organizational Affiliation
Haemek Hospital, Afula
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alexander Grinshpoon, MD, MHA, PhD
Organizational Affiliation
Shaar Menashe MHC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tirat Carmel Mental Health Center
City
Tirat Carmel
ZIP/Postal Code
30200
Country
Israel
12. IPD Sharing Statement
Learn more about this trial
Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients
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