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

Launched by GGZ NOORD-HOLLAND-NOORD · Dec 19, 2024

Keywords

ClinConnect Summary

This clinical trial aims to learn more about how the medication clozapine, used for treating severe schizophrenia that doesn't respond to other treatments, is processed in the body and how to best monitor its effects. Researchers want to understand how clozapine is converted into another substance called norclozapine in the liver, and how both these substances can cause side effects, such as cardiovascular issues and constipation. They will also look at various health factors, like blood sugar and cholesterol, and check if measuring clozapine levels in the blood 12 hours after taking the medication is the best way to ensure patients are getting the right amount.

To participate in this study, individuals must be between 18 and 70 years old and have been taking a stable dose of clozapine for at least one week. They should be able to provide informed consent, or if they are unable, their legal representative can do so. Participants will undergo blood tests to measure clozapine and norclozapine levels and will be monitored for side effects and symptoms related to their schizophrenia. This study is not yet recruiting, but it aims to help improve treatment for patients with therapy-resistant schizophrenia by finding ways to reduce side effects and enhance the effectiveness of clozapine.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 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).
• • At least two samples in the elimination phase of clozapine with both clozapine and norclozapine measured.
• • Measurement of the white cell count at least every three months or more often.
• • Routine metabolic screening performed at moment of inclusion.
• • Subjects should be able to understand the study information and procedures and give informed consent or when incapacitated subjects are not reliably able to give informed consent their legal representatives should give informed consent under the condition that these subjects are willing to participate.
• Exclusion Criteria:
• • 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.
• • Not sampled at Starlet (blood collection site) or sampled by dried blood spot
• • Unknown status of smoking (including vaping).
• • Unknown time of intake of clozapine.
• • Unknown time of blood sampling.
• • If informed consent is not obtained by the patient or by a legal representative in a mentally incapacitated patient, i.e. a legally incompetent adult.