Characterizing Response to Antipsychotics in Schizophrenia

Recruiting

• Conditions: Schizophrenia; Schizoaffective Disorder
• Interventions: Drug: Olanzapine; Drug: Clozapine

• Registration Number: NCT06159322
• Lead Sponsor: The Royal Ottawa Mental Health Centre

Brief Summary

The goal of this research project is to develop MRI-based biomarkers to identify patients with schizophrenia who are most likely to benefit from first-line antipsychotic or clozapine treatment. The MRI sequences (NM-MRI, MRS and rsfMRI) will be created by translating the best scientific evidence into a potential clinical product that has the highest chance of being clinically relevant predictor of treatment response. This study has the potential to significantly improve patient outcomes and reduce unnecessary interventions and costs at the Royal's Integrated Schizophrenia Recovery Program.

Detailed Description

Currently, we cannot predict who will get better on first-line antipsychotic versus clozapine treatment. Although much evidence shows that dopamine and glutamate function are related to treatment response in schizophrenia, the utility of neuromelanin sensitive MRI (NM-MRI) as a measure of dopamine and magnetic resonance spectroscopy (MRS) as a measure of glutamate \& glycine (a co-agonist of glutamate receptors) in predicting response to treatment have never been measured in the same sample. The evidence suggests that the function of these two neurotransmitter systems partially determines the response to antipsychotic medications. Additionally, an emerging type of resting-state functional MRI (rsfMRI), naturalistic movie-watching, has been shown to outperform traditional rsfMRI for functional connectivity-based prediction of behaviour and will be explored in the current study. Given the background information, our hypotheses are:

1.1) First-line antipsychotic users will have higher dopamine turnover resulting in a higher NM-MRI signal in the substantia nigra relative to clozapine users.

1.2) First-line antipsychotic users will have lower glutamate and/or glycine concentration as indicated by the MRS signal in the dorsal anterior cingulate relative to clozapine users.

Study Timeline

• Study First Submitted: 2022-04-10
• Study Start: 2023-01-01
• Status Verified: 2023-11
• Study First Submitted QC: 2023-11-28
• Last Update Submitted: 2023-11-28
• Study First Posted: 2023-12-06
• Last Update Posted: 2023-12-06
• Primary Completion: 2024-01-30
• Study Completion: 2024-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Are voluntary and competent to consent to the study
• Are between the ages of 18-55
• Are English literate
• Have a diagnosis of schizophrenia or schizoaffective disorder
• Are currently taking primarily olanzapine or clozapine

Exclusion Criteria

• Medication for the treatment of schizophrenia or schizoaffective disorder has changed in the past month
• Have a significant neurologic, neurodevelopmental, cardiovascular, renal, hepatic, hematological, gastrointestinal, pulmonary, or metabolic-endocrine disorder
• Are pregnant or breastfeeding
• Acquire positive urine test result for all drugs of abuse including cannabis
• Have met DSM-5 criteria for substance use disorder other than tobacco in the last 6 months
• Have a history of significant head trauma with loss of consciousness for more than 5 minutes
• Have any contraindication to MRI
• Have any other condition that in the opinion of the investigator(s) could create a hazard to the subject's safety, endanger the study procedures, or interfere with the interpretation of study results

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
First-line treatment group	Olanzapine	This group will consist of 20 patients with schizophrenia or schizoaffective disorder who are primarily prescribed olanzapine. Treatment will be carried out by the physicians within their circle of care, however, we will record their symptoms as they continue treatment.
Treatment-resistant group	Clozapine	This group will consist of 20 patients with schizophrenia or schizoaffective disorder who are primarily prescribed clozapine due to poor treatment response to first-line antipsychotic agents. Treatment will be carried out by the physicians within their circle of care, however, we will record their symptoms as they continue treatment.

Primary Outcome Measures

Name	Time	Method
Neuromelanin-sensitive magnetic resonance imaging (MRI) contrast-to-noise ratio (CNR)	Will be examined cross-sectionally on an as-recruited basis.	Indexes dopamine function
Glutamate/glycine magnetic resonance sptrectroscopy (MRS)	Will be examined cross-sectionally on an as-recruited basis.	Indexes glutamate \& glycine concentration

Trial Locations

Locations (1)

The Royal's Institute of Mental Health Research; 🇨🇦 Ottawa, Ontario, Canada