Characterizing Response to Antipsychotics in Schizophrenia

NCT ID: NCT06159322

Last Updated: 2023-12-06

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2024-01-30

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.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Antipsychotic treatment response

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

First-line treatment group

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.

Olanzapine

Intervention Type: DRUG

Antipsychotic medication

Treatment-resistant group

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.

Clozapine

Intervention Type: DRUG

Antipsychotic medication

Interventions

Olanzapine

Antipsychotic medication

Intervention Type: DRUG

Clozapine

Antipsychotic medication

Intervention Type: DRUG

Other Intervention Names

Zyprexa; Clozaril

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Royal's Institute of Mental Health Research

OTHER

Sponsor Role: collaborator

The Royal Ottawa Mental Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lauri Tuominen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The Royal's Institute of Mental Health Research

Clifford Cassidy, PhD

Role: PRINCIPAL_INVESTIGATOR

The Royal's Institute of Mental Health Research

Locations

The Royal's Institute of Mental Health Research

Ottawa, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Lauri Tuominen, MD, PhD

Role: CONTACT

Phone: (613) 722-6521

Email: Lauri.Tuominen@theroyal.ca

Coleka Masama, BSc

Role: CONTACT

Phone: (613) 722-6521

Email: coleka.masama@theroyal.ca

Facility Contacts

Alexis Dorland

Role: primary

Other Identifiers

2021033

Identifier Type: -

Identifier Source: org_study_id