Health TrialsbyHealthPanel

Nor)Clozapine Kinetics and Side Effects in Therapy Resistant Schizophrenia and the Optimal Sampling Time for Therapeutic Drug Monitoring

ConditionsCardiovascular Side Effects of ClozapineNeutropenia Due to ClozapineGeneral Side Effects of ClozapineConstipation Due to ClozapineSymptoms of SchizophreniaOptimal Blood Sampling Time for Clozapine in Patients Who Receive Clozapine Once and Twice DailyClozapine and Norclozapine Plasma Level Concentrations
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-70
SponsorGGZ Noord-Holland-Noord

About this trial

The goal of this observational study is to better understand how clozapine treatment can be tailored as regards minimizing side effects and optimizing efficacy and monitoring. Firstly, how clozapine is broken down into norclozapine in the liver and how both clozapine and norclozapine affect side effects are examined. In order to investigate this metabolization process in the liver inflammation levels in the blood are assessed, which inhibit the conversion of clozapine into norclozapine. In addition, various factors related to physical health are assessed, such as blood sugar, cholesterol, weight, waist circumference, blood pressure and heart rate. The role of hormones is investigated, such as cortisol, a stress hormone that affects metabolism and stress levels. Amino acids are examined, which are building blocks of proteins, and specific parts of DNA that influence clozapine metabolism. In addition, investigation follows whether 12 hours after ingestion is a well-chosen time at which the amount of clozapine is measured in the blood in case of ingestion once a day and twice a day. Finally, specific side effects of clozapine are assessed - with special attention to stool - and the severity of the psychiatric symptoms in patients with therapy resistant schizophrenia spectrum disorders.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Standard treatment of a stable, oral dose of clozapine for at least one week (at steady state).

Age between 18-70 years.

Registered time of intake as well as sampling time and dosage.

Registered smoking status (yes/no).

Disqualifiers

Pregnancy.

Malignancy or treatment with immunosuppressive medication.

Samples where cessation, start or dose change of interacting co-medication (such as valproic acid, gemfibrozil, fluvoxamine, omeprazole and cyclic oral contraceptives [21 on, 7 days off]) or changes in use of tobacco containing products occurred within seven days prior to blood sampling (21, 28, 34, 35).

Acute inflammation, infection or samples shortly after intoxication. In case this information is unknown, it may be derived by large unexpected change in levels compared to previous or target levels.

Trial population

The population includes adult patients (age between 18 and 70) with treatment resistant schizophrenia of schizoaffective disorder, treated with oral, once or twice-daily clozapine. Data will be collected from mental healthcare organization GGZ-NHN. All the patients have been treated with clozapine as part of standard care, as well as sampled routinely as part of standard care.

Trial design

Design model

Cohort

Time perspective

Other

Treatments tested in this trial

Not listed

Trial groups

60 Participants
are grouped into 1 trial group
Group A: Adult patients with treatment resistant schizophrenia spectrum disorders receiving clozapine.

Trial outcomes

Primary outcomes

1

Correlation between serum level HbA1c and (nor)clozapine concentrations and ratio.

Assessed using a PK-PD turn over model.

Time frame
For each patient two years of follow-up will be collected (until a maximum of 01-12-2027).

Secondary outcomes

1

Validation of an existing population pharmacokinetic model, assessing the validity of the current 12-hour post-intake sampling practice, determining the optimal sampling window for once-daily clozapine TDM.

The predictive performance of the model by Beex et al. (2023) for our population will be assessed through calculations of the prediction error for each observation as well as the root mean square error to measure the overall prediction accuracy. 2\. Percentage difference in clozapine and norclozapine median concentrations predicted 10, 11, 13 and 14-hour post intake (based on clinical samples) compared to median concentrations at current reference sampling time of 12-hour post intake. 3\. Percentage difference in clozapine and norclozapine concentrations based on different sampling times across entire concentration-time profiles to identify optimal sampling time or window within current therapeutic window of 350-700 μg/L.

Time frame
For the secondary endpoint pertaining to the sample times retrospective data will be collected from 01-02-2024 up to 01-02-2025.
2

The validity of the current 12-hour post-intake sampling practice.

Percentage difference in clozapine and norclozapine median concentrations predicted 10, 11, 13 and 14-hour post intake (based on clinical samples) compared to median concentrations at current reference sampling time of 12-hour post intake.

Time frame
For the secondary endpoint pertaining to the sample times retrospective data will be collected from 01-02-2024 up to 01-02-2025.
3

The optimal sampling window for once-daily clozapine therapeutic drug monitoring.

Percentage difference in clozapine and norclozapine concentrations based on different sampling times across entire concentration-time profiles to identify optimal sampling time or window within current therapeutic window of 350-700 μg/L.

Time frame
For the secondary endpoint pertaining to the sample times retrospective data will be collected from 01-02-2024 up to 01-02-2025.
4

The influence of demographic and clinical parameters on the pharmacokinetics and -dynamics of clozapine and norclozapine.

Effect of covariates on the pharmacokinetics of clozapine, the metabolite norclozapine (and clozapine/norclozapine ratio). Covariates to be studied include: age, estradiol, comedication (e.g. fluvoxamine), ethnicity, pharmacogenetics, smoking behaviour, inflammation markers, phenylalanine and tyrosine.

Time frame
For each patient two years of follow-up will be collected (until a maximum of 01-12-2027).

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

GGZ Noord-Holland-Noord

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: