SchizophreniaPhase 4NCT01663077
Clozapine Plasma Levels and the Relationship to the Genetic Polymorphism in Shizophrenic Patients
A Phase 4 study testing Clozapine in people with Schizophrenia, run by Tirat Carmel Mental Health Center at 1 site in Israel.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Clozapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteIsrael
- Study dates
- Oct 2012to Dec 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.].
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- Clozapine
- Keywords
- Clozapine, Schizophrenia, Remissia, polymorphism
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
Also called Leponex
A fixed dose of Clozapine 300 mg/day (150 mg x 2)for 3 month
| Study group | Role | What they receive |
|---|---|---|
| Clozapine | Experimental | Clozapine tablet 150 mg at the day and 150 mg in the evening by mouth per day for 3 month Receives: Drug: Clozapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clozapine steady state plasma level
Measured: 3 month
Secondary outcomes (1)
Polymorphism of CYP1A2, CYP3A4, CYP3A5 and CYP2D6 in clinically stable schizophrenic adult patients
Measured: Once
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2012 (estimated)
- Study startOct 2012
- Primary completionNov 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tirat Carmel Mental Health Center
- Sponsor type
- Other government
- 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
- Responsible party
- Principal investigator, Anatoly Kreinin, MD, PHD, Tirat Carmel Mental Health Center
- Investigators
- Anatoly Kreinin, MD, Phd, Study director, Tirat Carmel Mental Health CenterYedidia Bentur, MD, Principal investigator, Rambam Health Care Campus, HaifaNorberto Krivoy, MD, Principal investigator, Rambam Health Care Campus, HaifaDavid Rabinowitz, MD, Principal investigator, Rambam Health Care Campus, HaifaKamal Farhat, MD, Principal investigator, The Nazareth Hospital-EMMVladimir Lerner, MD, Phd, Principal investigator, Beersheva Mental Health CenterBoaz Bloch, MD, Principal investigator, Haemek Hospital, AfulaAlexander Grinshpoon, MD, MHA, PhD, Principal investigator, Shaar Menashe MHC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01663077
- Sponsor's protocol ID
- KBK2012
- Other IDs
- 03/11
- Status last verified
- Oct 2017
- First submitted
- 25 Jul 2012
- Last updated
- 12 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01663077
- Acronym / sponsor ID
- KBK2012
- Conditions
- Schizophrenia
- Keywords
- Clozapine, Schizophrenia, Remissia, polymorphism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Tirat Carmel Mental Health CenterOther government
- 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
- Study start
- Oct 2012
- Primary completion
- Nov 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 13 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clozapine | Experimental | Drug: ClozapineClozapine tablet 150 mg at the day and 150 mg in the evening by mouth per day for 3 month |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.].
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClozapineAlso: LeponexA fixed dose of Clozapine 300 mg/day (150 mg x 2)for 3 month | Drug | Clozapine |
Primary outcome
Clozapine steady state plasma level
Time frame: 3 month
1 secondary outcome
Polymorphism of CYP1A2, CYP3A4, CYP3A5 and CYP2D6 in clinically stable schizophrenic adult patients
Time frame: Once
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anatoly Kreinin, MD, Phd study director
Tirat Carmel Mental Health Center
Yedidia Bentur, MD principal investigator
Rambam Health Care Campus, Haifa
Norberto Krivoy, MD principal investigator
Rambam Health Care Campus, Haifa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clozapine in people with Schizophrenia, run by Tirat Carmel Mental Health Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clozapine steady state plasma level (time frame: 3 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2017.