- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02714894
Response to Clozapine in Treatment Resistant Schizophrenia: A Longitudinal Magnetic Resonance Spectroscopy Study
June 2, 2022 updated by: Ariel Graff, Centre for Addiction and Mental Health
Glutamatergic System and Response to Clozapine in Patients With Treatment-Resistant Schizophrenia: a Prospective Proton Magnetic Resonance Spectroscopy Study
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.
Study Overview
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 Type
Observational
Enrollment (Anticipated)
108
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5T 1R8
- Centre for Addiction and Mental Health
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
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 are starting clozapine will be recruited.
A sample of healthy controls will also be recruited.
Description
Inclusion Criteria for Participants with TRS:
- DSM-IV/SCID diagnosis of schizophrenia, schizoaffective disorder, delusional disorder, or psychotic disorder NOS.
- Age 18 years or older at time of scanning
- History of failure to respond to at least two previous sequential antipsychotic treatments different to clozapine, each attaining a chlorpromazine daily dose of≥ 400 mg for a duration ≥ 6 consecutive weeks.Long-acting antipsychotic treatment will not be allowed during the last trial prior to clozapine in order to avoid residual concentrations or effects.Failure of treatment will be defined by a Clinical Global Impression Severity (CGI-Severity) score of ≥4 and score of ≥4 on 2 Positive and Negative Syndrome Scale (PANSS) positive symptom items. The CGI-Severity or Global Assessment of Functioning (GAF) will be completed retrospectively based on information provided by the participant, participant's psychiatrist, medical chart, or other sources of available collateral information.
Exclusion Criteria for Participants with TRS:
- Incapacity to provide consent to participate in the research study.
- Substance abuse or dependence (within past six months), excluding nicotine and caffeine.
- Positive urine drug screen for drugs of abuse.
- Metal implants or a pace-maker that would preclude the MRI scan.
- History of head trauma resulting in loss of consciousness > 30 minutes that required medical attention.
- Unstable physical illness or significant neurological disorder including a seizure disorder.
- Size of head, neck, and body being unable to fit MRI scanners.
- Refusal to provide consent to investigator to communicate with physician of record to obtain collateral information.
- Psychiatric concerns raised by the physician of record regarding participation in the study.
- Currently taking medications that may directly impact the glutamatergic system (i.e. lamotrigine, topiramate, memantine or N-acetylcysteine)
- ECT, MST or TMS in the past 6 months
Inclusion criteria for Healthy Controls:
- Age of 18 and older at time of scanning
- Being capable to consent to study procedures
- Absence of history of psychiatric illness using the Mini-International Neuropsychiatric Interview (MINI)
Exclusion criteria for Healthy Controls:
- First degree family member with primary psychotic disorder
- Substance abuse or dependence (within past six months), excluding nicotine and caffeine.
- Positive urine drug screen for drugs of abuse
- Pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or any other conditions that would preclude the MRI scan
- Clinically significant claustrophobia
- History of head trauma resulting in loss of consciousness > 30 minutes that required medical attention
- Size of head, neck, and body being unable to fit MRI scanners
- Unstable physical illness or significant neurological disorder including a seizure disorder
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Clozapine Responders (Non-URS)
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. |
Patient participants will be starting clozapine as part of their clinical care.
Other Names:
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Clozapine Non-Responders (URS)
Definition of URS
|
Patient participants will be starting clozapine as part of their clinical care.
Other Names:
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Healthy Controls
Healthy controls will be matched as closely as possible on age and gender with participants in the patient groups.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in 1H-MRS glutamatergic metabolites before and after clozapine.
Time Frame: Change from baseline (pre-clozapine) of 1H-MRS glutamatergic metabolites at 12 weeks
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1H-MRS will be employed to quantify glutamatergic metabolites, specifically glutamate, glutamine, glx and glutathione.
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Change from baseline (pre-clozapine) of 1H-MRS glutamatergic metabolites at 12 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Ariel Graff, MD, PhD, Centre for Addiction and Mental Health
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2016
Primary Completion (Anticipated)
July 30, 2022
Study Completion (Anticipated)
July 30, 2022
Study Registration Dates
First Submitted
March 14, 2016
First Submitted That Met QC Criteria
March 16, 2016
First Posted (Estimate)
March 22, 2016
Study Record Updates
Last Update Posted (Actual)
June 3, 2022
Last Update Submitted That Met QC Criteria
June 2, 2022
Last Verified
June 1, 2022
More Information
Terms related to this study
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
- 122-2015
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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