The Significance of Deviation in Time From the 12-hour Standard Serum-clozapine Monitoring.

Study Overview
=================
Brief Summary
-----------------
The role of Therapeutic Drug Monitoring (TDM) in clozapine dose adjustment have been debated. Blood samples for s-clozapine monitoring should be drawn 12 hours post dose. The scope of this trial is to describe changes of s-clozapine and s-N-desmethyl-clozapine within the range of 10-14 hours after the last administration of clozapine .

Detailed Description
-----------------
Several factors can influence s-clozapine and thereby the occurence of dose-related adverse reactions and level of treatment response. The role of Therapeutic Drug Monitoring (TDM) in clozapine dose adjustment have been debated. Blood samples for s-clozapine monitoring are recommended to be drawn 12 hours post dose. Uncertainty regarding the timing of blood sampling and the individual pharmakokinetics for clozapine +/- 2 hours from the 12-hour timepoint, leads to uncertainty regarding the comparability of serum concentrations and the information hold within them. The scope of this trial is to describe changes of s-clozapine and s-N-desmethyl-clozapine within the range of 10-14 hours after the last administration of clozapine . In addition we want to investigate if any of the following covariates might affect the change of s-clozapine and s-N-desmethyl-clozapine: Sex, age, BMI, co-medications, signs of infection, caffeine intake and smoking.

Official Title
-----------------
The Significance of Deviation in Time From the 12-hour Standard Serum-clozapine Monitoring

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Procedure: Blood sampling
* Drug: Clozapine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 < 65 Diagnosed with schizophrenia according to the criteria of ICD10 (International Classification of Diseases, World Health Organization) or the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the American Psychiatric Association) Unchanged dose of clozapine for the last 30 days Usual time of clozapine evening-dose administration between 9 and 12 pm. Exclusion Criteria: Significant drug or alcohol abuse that affects participation in this trial Non- or partial compliance of clozapine the day before the trial (assessed by interview) Unresponsive by telephone the evening before the trial Consumption of clozapine in the morning on the day of the trial Significant change in smoking habits within the last 30 days (assessed by interview) Significant change of caffeine intake within the last 7 days (assessed by interview) Modified use of other antipsychotics within the last 30 days Within the last 30 days (7 days for hormone based contraceptives) changes in the use of other medications that can affect s- clozapine during the trial : ( fluvoxamine, ciprofloxacin, hormone based contraceptives, carbamazepine , phenytoin , rifampicin, omeprazole ) Females who are pregnant or breast-feeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clozapine<br>treatment as usual: administration of clozapine between 9 and 12 pm. Blood sampling 10 -14 hours post drug administration | Procedure: Blood sampling<br>* blood samples for s-clozapine and s-desmethyl-clozapine analysis are collected at 10, 11, 12, 13 and 14 hours post evening-clozapine-administration<br>Drug: Clozapine<br>* Registration of the exact time of drug administration. Also postponement of any morning clozapine administration until ended blood sampling.<br>* Other names: Leponex;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in serum-clozapine |  | 10 - 14 hours post drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in serum-clozapine (multiple shorter ranges) |  | < 10 -14 hours post dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizophrenia, Clozapine, TDM, Serum Concentration