Response to Clozapine in Treatment Resistant Schizophrenia: A Longitudinal Magnetic Resonance Spectroscopy Study

• Conditions: Schizophrenia
• Interventions: Drug: Clozapine

• Registration Number: NCT02714894
• Lead Sponsor: Centre for Addiction and Mental Health

Brief Summary

The purpose of this study is to investigate the relationship between glutamate and related brain chemicals and treatment response to clozapine in patients with treatment-resistant schizophrenia.

Detailed Description

This study will be a prospective proton spectroscopy (1H-MRS) study designed to compare the levels of glutamate, glutamine, glx, and glutathione in age- and gender- matched patients with poor response to clozapine (URS), patients with good response to clozapine (non-URS), and healthy controls. Participants with schizophrenia who fail to respond to optimal treatment with at least two different non-clozapine antipsychotics (i.e. treatment-resistant schizophrenia \[TRS\]) and who are starting clozapine as part of their clinical care will be recruited. A sample of healthy controls will also be recruited. Participants with TRS will have two 1H-MRS scans. The 1H-MRS scan will be performed within 1 week and 12 weeks after clozapine initiation. Clinical assessments will be performed within 1 week of each 1H-MRS scan and after 6 weeks of clozapine treatment. Cognitive assessments will also be performed within 1 week of 1H-MRS scans. Healthy controls will also undergo two 1H-MRS scans with a 12-week interval. Cognitive assessments will also be performed within 1 week of 1H-MRS scans.

Study Timeline

• Study First Submitted: 2016-03-14
• Study First Submitted QC: 2016-03-16
• Study First Posted: 2016-03-22
• Study Start: 2016-04
• Status Verified: 2022-06
• Last Update Submitted: 2022-06-02
• Last Update Posted: 2022-06-03
• Primary Completion: 2022-07-30
• Study Completion: 2022-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Clozapine Responders (Non-URS)	Clozapine	Definition of non-URS (1) ≥30% decrease in the PANSS positive subscale score, CGI-severity ≤3 and CGI-Improvement ≤2 after 12 weeks of treatment.
Clozapine Non-Responders (URS)	Clozapine	Definition of URS 1. Taking clozapine for ≥ 12 weeks, attaining a plasma clozapine level ≥350 ng/ml. 2. CGI-Severity score of ≥4 and score of ≥4 on 2 PANSS positivesymptom items.

Primary Outcome Measures

Name	Time	Method
Change in 1H-MRS glutamatergic metabolites before and after clozapine.	Change from baseline (pre-clozapine) of 1H-MRS glutamatergic metabolites at 12 weeks	1H-MRS will be employed to quantify glutamatergic metabolites, specifically glutamate, glutamine, glx and glutathione.

Trial Locations

Locations (1)

Centre for Addiction and Mental Health; 🇨🇦 Toronto, Ontario, Canada