Trials / Not Yet Recruiting

Not Yet RecruitingNCT06749041

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

Clozapine OpTimal Timing for Optimal moNitoring and Side Effects

Status: Not Yet Recruiting
Phase: —
Study type: Observational
Enrollment: 60 (estimated)

Sponsor: GGZ Noord-Holland-Noord · Academic / Other
Sex: All
Age: 18 Years – 70 Years
Healthy volunteers: Not accepted

Summary

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.

Detailed description

Rationale: Therapeutic drug monitoring (TDM) is essential for clozapine and can enhance therapeutic outcomes and minimize side effects. As of yet, research on (nor)clozapine concentrations and their association to metabolic side effects is limited and inconclusive. Unfortunately, not enough is known about individual risk factors for developing metabolic side effects to personalize clozapine treatment. It would be desirable to have another way to predict which clozapine users are at increased risk of developing severe side effects. Current guidelines are based on limited evidence, potentially resulting in inconsistent or suboptimal monitoring and management. Objective: The primary objective is to evaluate the correlation between (nor)clozapine kinetics and serum level HbA1c. Secondary objectives include validating 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 and assessing the correlation of other metabolic and multiple laboratory parameters and influence of demographic and clinical parameters on the pharmacokinetics and -dynamics of clozapine and norclozapine.

Conditions

Timeline

Start date: 2024-12-23
Primary completion: 2027-12-01
Completion: 2027-12-01
First posted: 2024-12-27
Last updated: 2024-12-30

Source: ClinicalTrials.gov record NCT06749041. Inclusion in this directory is not an endorsement.