SchizophreniaNCT02714894
Response to Clozapine in Treatment Resistant Schizophrenia: A Longitudinal Magnetic Resonance Spectroscopy Study
An observational study of Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Clozapine
- How many people
- 108 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2016to 30 Jul 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
- 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)
Who cannot join
- 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.
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- 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
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- Clozapine
- Keywords
- magnetic resonance imaging, magnetic resonance spectroscopy
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClozapineDrug
Also called Clozaril
Patient participants will be starting clozapine as part of their clinical care.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Clozapine | |
| Healthy Controls | Healthy controls will be matched as closely as possible on age and gender with participants in the patient groups. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline (pre-clozapine) of 1H-MRS glutamatergic metabolites at 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2016 (estimated)
- Study startApr 2016
- Primary completion30 Jul 2022 (estimated)
- Study completion30 Jul 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 108 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Ariel Graff, Centre for Addiction and Mental Health
- Investigators
- Ariel Graff, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02714894
- Sponsor's protocol ID
- 122-2015
- Status last verified
- Jun 2022
- First submitted
- 14 Mar 2016
- Last updated
- 3 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamatergic System and Response to Clozapine in Patients With Treatment-Resistant Schizophrenia: a Prospective Proton Magnetic Resonance Spectroscopy Study
- ClinicalTrials.gov ID
- NCT02714894
- Acronym / sponsor ID
- 122-2015
- Conditions
- Schizophrenia
- Keywords
- magnetic resonance imaging, magnetic resonance spectroscopy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 108 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Apr 2016 (actual)
- Primary completion
- 30 Jul 2022 (estimated)
- Study completion
- 30 Jul 2022 (estimated)
- First posted
- 22 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Clozapine Responders (Non-URS) | – | Drug: ClozapineDefinition 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) | – | Drug: ClozapineDefinition 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. |
| Healthy Controls | – | –Healthy controls will be matched as closely as possible on age and gender with participants in the patient groups. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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.
- Age of 18 and older at time of scanning
- Being capable to consent to study procedures
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClozapineAlso: ClozarilPatient participants will be starting clozapine as part of their clinical care. | Drug | Clozapine Non-Responders (URS), Clozapine Responders (Non-URS) |
Primary outcome
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
1H-MRS will be employed to quantify glutamatergic metabolites, specifically glutamate, glutamine, glx and glutathione.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2022.
- 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 worldLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ariel Graff, MD, PhD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Schizophrenia, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2022.