Therapeutic Drug Monitoring for Individualized Clozapine Therapy

A Clinical Trial to Investigate the Factors Affecting Adverse Drug Reactions and Clinical Efficacy of Clozapine in Korean

The purpose of this study is to evaluate the factors affecting the occurrence of adverse drug reactions (glucose and lipid metabolism abnormality, changes in liver function index and sleeping tendency) and clinical effects in schizophrenia patients with clozapine treatment

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Clozapine

Detailed Description

1. The baseline tests (sleeping tendency assessment, clinical symptom and cognitive assessments, clinical laboratory tests, genotyping, exploratory biomarker tests, etc.) are conducted to the schizophrenia patients before initiation of the clozapine dosing.
2. On day 15 and 57, the changes from baseline clinical symptom and cognitive function are assessed after clozapine treatment. Also, the occurrence of adverse drug reactions are evaluated. In addition, blood sample collections are performed for the assessment of clozapine and its metabolite levels.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Euitae Kim, Ph. D.; Phone Number: +82-31-787-7435; Email: euitae.kim@gmail.com

Study Locations

• Korea, Republic of
  • Seongnam, Korea, Republic of, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
    • Contact: Seoyoung Kim, MD; Phone Number: 031-787-8219; Email: zentiana0@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who are diagnosed with schizophrenia spectrum disorder and are expected to use clozapine for more than 57 days to treat or prevent recurrence of schizophrenia

Description

Inclusion Criteria:

1. Patients who are diagnosed with schizophrenia spectrum disorder and are expected to use clozapine for more than 57 days to treat or prevent recurrence of schizophrenia
2. Patients who are 19 years or older
3. Patient who understands the contents of the clinical research and provide their written informed consent forms

Exclusion Criteria:

1. Patients taking a drug that the researcher deems inappropriate before clozapine administration
2. Patients who can not use an appropriate contraceptive method during the study period
3. Patients whom the researcher deemed inappropriate for clinical research participation

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose and lipid metabolism abnormality	Change from baseline glucose and lipid profiles after clozapine administration	Change from baseline glucose and lipid profiles on Day 15, and 57
Liver function abnormality	Change from baseline liver function test	Change from baseline liver function test on Day 15, and 57
Sleeping tendency assessment	Epworth sleepiness scale (ESS).; ESS is comprised of eight questions, each asking about the subject's likelihood of dozing off or falling asleep in a particular situation that is commonly met in daily life.; Each ESS item score measures a particular "situational sleep propensity", and respondents use a four-point scale from 0 (no chance of dozing/falling asleep) to 3 (high chance of dozing/falling asleep) for each of the eight questions.; The sum of eight item scores (the total ESS score) measures the subject's average sleep propensity across those different situations in daily life. A total ESS score of 16-24 points indicates severe excessive daytime sleepiness.	Change from baseline sleeping tendency assessment on Day 15, and 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function assessment	MCCB (MATRICS Consensus Cognitive Battery).	Change from baseline MCCB on Day 57, and 127
Clinical symptom assessment	Brief Psychiatric Rating Scale (BPRS).; BPRS is a 24-item scale that measures psychiatric symptoms such as depression, anxiety, hallucinations and unusual behaviour.; Each symptom is rated on a scale from 1(not present) to 7(extremely severe).; The sum of all 24 items is then calculated to a maximum score of 168. The higher the score, the more psychiatrically impaired the patient is.	Change from baseline BPRS on Day 15, and 57

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood clozapine and its metabolite level	Relationship between occurrence of clozapine adverse drug reactions and clozapine blood concentration	On Day 15, and 57 after clozapine dosing

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Study Chair: Sang-In Park, Ph. D., Kyung Hee University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 13, 2018
• Primary Completion (ANTICIPATED): November 30, 2020
• Study Completion (ANTICIPATED): December 31, 2020

Study Registration Dates

• First Submitted: May 1, 2018
• First Submitted That Met QC Criteria: May 1, 2018
• First Posted (ACTUAL): May 14, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 24, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: quality of life; genetic polymorphism; adverse drug reaction; pharmacodynamic variability; personalized pharmacotherapy
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; GABA Agents; GABA Antagonists; Clozapine
• Other Study ID Numbers: CLZ_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED