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

NCT02714894 | Unknown

• 1 other identifier: 122-2015
• Study Type: observational
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Keywords

magnetic resonance imaging; magnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (1)

• Change in 1H-MRS glutamatergic metabolites before and after clozapine.

  1H-MRS will be employed to quantify glutamatergic metabolites, specifically glutamate, glutamine, glx and glutathione.

  Change from baseline (pre-clozapine) of 1H-MRS glutamatergic metabolites at 12 weeks

Study Arms (3)

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.

Drug: Clozapine

Clozapine Non-Responders (URS)

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.

Drug: Clozapine

Healthy Controls

Healthy controls will be matched as closely as possible on age and gender with participants in the patient groups.

Interventions

Clozapine DRUG

Patient participants will be starting clozapine as part of their clinical care.

Also known as: Clozaril

Clozapine Non-Responders (URS); Clozapine Responders (Non-URS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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)
• First degree family member with primary psychotic disorder

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Related Links

• The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample

MeSH Terms

Conditions

Schizophrenia

Interventions

Clozapine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ariel Graff, MD, PhD

  Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ariel Graff MD, PhD

Study Record Dates

• First Submitted: March 14, 2016
• First Posted: March 22, 2016
• Study Start: April 1, 2016
• Primary Completion: July 30, 2022
• Study Completion: July 30, 2022
• Last Updated: June 3, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)