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

NCT01663077 | Completed Phase 4

• 2 other identifiers: KBK201203/11
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Clozapine steady state plasma level

  3 month

Secondary Outcomes (1)

• Polymorphism of CYP1A2, CYP3A4, CYP3A5 and CYP2D6 in clinically stable schizophrenic adult patients

  Once

Study Arms (1)

Clozapine

EXPERIMENTAL

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

Drug: Clozapine

Interventions

Clozapine DRUG

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

Also known as: Leponex

Clozapine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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. \[Female patients will also have a pregnancy test.\].

Sponsors & Collaborators

• Tirat Carmel Mental Health Center: lead
• Technion, Israel Institute of Technology: collaborator
• Ben-Gurion University of the Negev: collaborator
• Beersheva Mental Health Center: collaborator
• Sha'ar Menashe Mental Health Center: collaborator
• HaEmek Medical Center, Israel: collaborator
• The Nazareth Hospital, Israel: collaborator

Study Sites (1)

Tirat Carmel Mental Health Center

Tirat Carmel, 30200, Israel

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Clozapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Anatoly Kreinin, MD, Phd

  Tirat Carmel Mental Health Center

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Psychiatric Department

Study Record Dates

• First Submitted: July 25, 2012
• First Posted: August 13, 2012
• Study Start: October 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: October 12, 2017

Record last verified: 2017-10

Locations

IL (1)