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

NCT ID: NCT01663077

Last Updated: 2017-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-12-31

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.

Conditions

Schizophrenia

Keywords

Clozapine; Schizophrenia; Remissia; polymorphism

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Clozapine

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

Group Type: EXPERIMENTAL

Clozapine

Intervention Type: DRUG

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

Interventions

Clozapine

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

Intervention Type: DRUG

Other Intervention Names

Leponex

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.].

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technion, Israel Institute of Technology

OTHER

Sponsor Role: collaborator

Ben-Gurion University of the Negev

OTHER

Sponsor Role: collaborator

Beersheva Mental Health Center

OTHER_GOV

Sponsor Role: collaborator

Sha'ar Menashe Mental Health Center

OTHER

Sponsor Role: collaborator

HaEmek Medical Center, Israel

OTHER

Sponsor Role: collaborator

The Nazareth Hospital, Israel

OTHER

Sponsor Role: collaborator

Tirat Carmel Mental Health Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Anatoly Kreinin, MD, PHD

Director of Psychiatric Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anatoly Kreinin, MD, Phd

Role: STUDY_DIRECTOR

Tirat Carmel Mental Health Center

Yedidia Bentur, MD

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus, Haifa

Norberto Krivoy, MD

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus, Haifa

David Rabinowitz, MD

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Campus, Haifa

Kamal Farhat, MD

Role: PRINCIPAL_INVESTIGATOR

The Nazareth Hospital-EMM

Vladimir Lerner, MD, Phd

Role: PRINCIPAL_INVESTIGATOR

Beersheva Mental Health Center

Boaz Bloch, MD

Role: PRINCIPAL_INVESTIGATOR

Haemek Hospital, Afula

Alexander Grinshpoon, MD, MHA, PhD

Role: PRINCIPAL_INVESTIGATOR

Shaar Menashe MHC

Locations

Tirat Carmel Mental Health Center

Tirat Carmel, , Israel

Countries

Israel

Other Identifiers

03/11

Identifier Type: OTHER

Identifier Source: secondary_id

KBK2012

Identifier Type: -

Identifier Source: org_study_id