SchizophreniaNCT06278246
Investigating the Muscarinic System in Schizophrenia Using Positron Emission Tomography
An observational study of Schizophrenia and Schizophreniform Disorders, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Within the schizophrenia population, there are individuals that respond to first-line antipsychotic treatments while others do not. The availability of muscarinic M4 subtype receptors (M4R) may play a role as to whether a person with schizophrenia is responsive to first-line antipsychotics or not. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Schizophreniform Disorders
- What is being tested?
- PET Scan
- Type of treatment
- Surgery or procedure
- How many people
- 58 participants
- Where
- 1 siteCanada
- Study dates
- 11 Mar 2024to Mar 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: Antipsychotic-free patients with schizophrenia or schizophreniform disorder and healthy controls
Who may be able to join
- Criteria for both Patients with Schizophrenia and Healthy Controls:
- Age of 18 years and older
- Willing to consent to study procedures
- Criteria for Patients with Schizophrenia:
- Inpatients or outpatients ≥18 years of age.
- DSM-V diagnosis of schizophrenia or schizophreniform disorder confirmed using SCID-5.
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- Capable of consenting to participate in the research study (MacCAT).
- No exposure to long-acting antipsychotics in the past 6 months and oral antipsychotic-free for at least 2-weeks
- Deemed suitable to receive first-line antipsychotic treatment as standard of care by the treating physician.
- Criteria for Healthy Controls:
- Absence of history of psychiatric illness using the SCID-5
- Do not have any first-degree family members with a primary psychotic disorder.
- Are willing to attend appointments reliably.
- Are capable of providing consent
Who cannot join
- Participants will be excluded if they meet ANY of the criteria listed below:
- DSM-V diagnosis of schizoaffective disorder or psychosis not otherwise specified.
- Unstable medical illness or any concomitant major medical or neurological illness, including a history of seizures and traumatic head injury resulting in a loss of consciousness > 30 minutes that required medical attention.
- Acute suicidal and/or homicidal ideation.
- DSM-V substance use disorder (except caffeine and nicotine) within one month prior to study entry.
- Positive urine drug screen for drugs of abuse at the screening visit (excluding cannabis and/or benzodiazepines).
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- Reporting the chronic use of medication with muscarinic mechanism of action.
- Pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or any other conditions that would preclude the MRI scan
- Pregnancy (Note: Females up to age 65 must have negative urine pregnancy test at screening), or breastfeeding.
- If participation in the study would expose participants to more than the annual radiation dose limit (20 mSv) for human subjects participating in research studies, or if the potential participant already underwent a number of PET scans that, including the PET scans under this protocol, will bring the total to more than 8 PET scans /lifetime. For example, participants known to have already been exposed to radiation through X-rays, CT-scans, or other nuclear medicine procedures during the last year may have already surpassed, or will surpass via study participation, the annual radiation dose limit and thus be excluded.
- Clinically significant claustrophobia
- Size of head, neck, and body being unable to fit MRI or PET scanners (e.g. body weight of 350 pounds).
- Blood or coagulation disorders, or taking anticoagulant medication (not antiplatelet).
- Patients with Schizophrenia will also be excluded if they meet ANY of the criteria listed below:
- Refusal to give consent to investigator to communicate with treating physician for entire duration of the study.
- Previous clozapine treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Muscarinic Hypothesis of Schizophrenia: an [11C]MK-6884 PET Study Study Protocol
Within the schizophrenia population, there are individuals that respond to first-line antipsychotic treatments while others do not. The availability of muscarinic M4 subtype receptors (M4R) may play a role as to whether a person with schizophrenia is responsive to first-line antipsychotics or not. The goal of this observational study is to compare the availability of M4R in antipsychotic-free patients with schizophrenia and matched healthy controls. In addition, M4R availability in schizophrenia patients will be examined in relation to response to first line antipsychotics and clinical and cognitive measures. This study may help better understand antipsychotic resistance in schizophrenia and lead to the development of new treatment options, particularly for cognitive deficits and negative symptoms.
Read the detailed description
This study is composed of two participant groups. 1) Antipsychotic-free patients with schizophrenia and 2) healthy matched controls. The healthy controls will be matched as closely as possible for age, sex, cannabis, and nicotine consumption to the patient group. All participants will undergo a positron emission tomography (PET) scan to measure the M4R binding with [11C]MK-6884 and examine its relationship with clinical and cognitive measures.
Participants who meet the inclusion and exclusion criteria at screening visit (visit 1) will be enrolled into the study. All participants will undergo a PET scan with the novel tracer [11C]MK-6884 to examine its binding with M4R. The third visit will consist of a MRI scan and cognitive assessments. Participants with schizophrenia will have visit four, which occurs 6 weeks after the first antipsychotic trial, initiated by their treating physician. If the treating physician starts a second antipsychotic trial, then a visit five occurs 6 weeks after the second trial. Both visits four and five involve clinical and cognitive assessments.
- Conditions
- Schizophrenia, Schizophreniform Disorders
- Being tested
- PET Scan
- Keywords
- Magnetic resonance imaging, Positron emission tomography, Antipsychotic-free
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET ScanRadiation
PET scan using the novel [11C]MK-6884 tracer to measure M4R during the antipsychotic-free state
| Study group | Role | What they receive |
|---|---|---|
| Patients with Schizophrenia | Antipsychotic-free patients with schizophrenia or schizophreniform disorder Receives: Radiation: PET Scan | |
| Healthy Controls | Healthy controls matched for age, sex, cannabis, and nicotine consumption to the 29 patients Receives: Radiation: PET Scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
M4 receptor expression
Regional [11C]MK-6884 uptake will be quantified as volume of distribution (VT) and binding potential relative to non-displaceable compartment (BPND), as defined by consensus nomenclature for in vivo imaging of reversibly binding radioligands. Ichise's multilinear analysis (MA1) method will be employed to quantify VT, using arterial blood sampling. The simplified reference tissue model (SRTM) will be used to estimate BPND, using the cerebellum as a reference region.
Measured: At baseline
Clinical Data Statistical Analysis
Exploratory correlations will be performed between clinical symptoms and whole brain VT within the patient group.
Measured: At baseline and 6 week Follow-up after antipsychotic trial
Secondary outcomes (2)
Statistical Analysis of Cognitive Data
Correlations will be analyzed between memory performance and dorsal striatal VT within the patient group and healthy control group, respectively. Exploratory correlations will be performed between all other cognitive measures and whole brain VT within each group, separately.
Measured: At baseline and 6 week Follow-up after antipsychotic trial (only for patient group)
Statistical Analysis of Psychopathological Personality Traits in Health Control Group
Correlations will be performed between trait impulsivity and ventral striatal VT within the healthy control group. Exploratory correlations will be performed between all other personality trait measures and whole brain VT
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2024
- Study start11 Mar 2024
- Primary completionMar 2026 (estimated)
- Study completionMar 2026 (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
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ariel Graff, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06278246
- Sponsor's protocol ID
- 050/2021
- Status last verified
- Mar 2025
- First submitted
- 15 Feb 2024
- Last updated
- 28 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Muscarinic Hypothesis of Schizophrenia: an [11C]MK-6884 PET Study Study Protocol
- ClinicalTrials.gov ID
- NCT06278246
- Acronym / sponsor ID
- 050/2021
- Conditions
- Schizophrenia, Schizophreniform Disorders
- Keywords
- Magnetic resonance imaging, Positron emission tomography, Antipsychotic-free
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- 11 Mar 2024 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 26 Feb 2024 (actual)
- 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.
Within the schizophrenia population, there are individuals that respond to first-line antipsychotic treatments while others do not. The availability of muscarinic M4 subtype receptors (M4R) may play a role as to whether a person with schizophrenia is responsive to first-line antipsychotics or not. The goal of this observational study is to compare the availability of M4R in antipsychotic-free patients with schizophrenia and matched healthy controls. In addition, M4R availability in schizophrenia patients will be examined in relation to response to first line antipsychotics and clinical and cognitive measures. This study may help better understand antipsychotic resistance in schizophrenia and lead to the development of new treatment options, particularly for cognitive deficits and negative symptoms.
Detailed description
This study is composed of two participant groups. 1) Antipsychotic-free patients with schizophrenia and 2) healthy matched controls. The healthy controls will be matched as closely as possible for age, sex, cannabis, and nicotine consumption to the patient group. All participants will undergo a positron emission tomography (PET) scan to measure the M4R binding with [11C]MK-6884 and examine its relationship with clinical and cognitive measures.
Participants who meet the inclusion and exclusion criteria at screening visit (visit 1) will be enrolled into the study. All participants will undergo a PET scan with the novel tracer [11C]MK-6884 to examine its binding with M4R. The third visit will consist of a MRI scan and cognitive assessments. Participants with schizophrenia will have visit four, which occurs 6 weeks after the first antipsychotic trial, initiated by their treating physician. If the treating physician starts a second antipsychotic trial, then a visit five occurs 6 weeks after the second trial. Both visits four and five involve clinical and cognitive assessments.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with Schizophrenia | – | Radiation: PET ScanAntipsychotic-free patients with schizophrenia or schizophreniform disorder |
| Healthy Controls | – | Radiation: PET ScanHealthy controls matched for age, sex, cannabis, and nicotine consumption to the 29 patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Antipsychotic-free patients with schizophrenia or schizophreniform disorder and healthy controls
Key inclusion criteria (14 listed)
- Age of 18 years and older
- Willing to consent to study procedures
- Inpatients or outpatients ≥18 years of age.
- DSM-V diagnosis of schizophrenia or schizophreniform disorder confirmed using SCID-5.
- Capable of consenting to participate in the research study (MacCAT).
Key exclusion criteria (16 listed)
- DSM-V diagnosis of schizoaffective disorder or psychosis not otherwise specified.
- Unstable medical illness or any concomitant major medical or neurological illness, including a history of seizures and traumatic head injury resulting in a loss of consciousness > 30 minutes that required medical attention.
- Acute suicidal and/or homicidal ideation.
- DSM-V substance use disorder (except caffeine and nicotine) within one month prior to study entry.
- Positive urine drug screen for drugs of abuse at the screening visit (excluding cannabis and/or benzodiazepines).
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 |
|---|---|---|
| PET ScanPET scan using the novel [11C]MK-6884 tracer to measure M4R during the antipsychotic-free state | Radiation | Healthy Controls, Patients with Schizophrenia |
Primary outcome
M4 receptor expression
Time frame: At baseline
Regional [11C]MK-6884 uptake will be quantified as volume of distribution (VT) and binding potential relative to non-displaceable compartment (BPND), as defined by consensus nomenclature for in vivo imaging of reversibly binding radioligands. Ichise's multilinear analysis (MA1) method will be employed to quantify VT, using arterial blood sampling. The simplified reference tissue model (SRTM) will be used to estimate BPND, using the cerebellum as a reference region.
Clinical Data Statistical Analysis
Time frame: At baseline and 6 week Follow-up after antipsychotic trial
Exploratory correlations will be performed between clinical symptoms and whole brain VT within the patient group.
2 secondary outcomes
Statistical Analysis of Cognitive Data
Time frame: At baseline and 6 week Follow-up after antipsychotic trial (only for patient group)
Statistical Analysis of Psychopathological Personality Traits in Health Control Group
Time frame: At baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2025.
- Description 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.Link 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 and Schizophreniform Disorders, 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 14 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 28 Mar 2025. 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?
This study is still under way. Results are not available in the source record yet.
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?
M4 receptor expression (time frame: At baseline). The study lists 2 primary outcomes in all. 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 28 Mar 2025.