Investigating the Muscarinic System in Schizophrenia Using Positron Emission Tomography

NCT06278246 | Active Not Recruiting

• 1 other identifier: 050/2021
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Schizophrenia; Schizophreniform Disorders

Keywords

Magnetic resonance imaging; Positron emission tomography; Antipsychotic-free

Outcome Measures

Primary Outcomes (2)

• 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.

  At baseline

• Clinical Data Statistical Analysis

  Exploratory correlations will be performed between clinical symptoms and whole brain VT within the patient group.

  At baseline and 6 week Follow-up after antipsychotic trial

Secondary Outcomes (2)

• Statistical Analysis of Cognitive Data

  At baseline and 6 week Follow-up after antipsychotic trial (only for patient group)

• Statistical Analysis of Psychopathological Personality Traits in Health Control Group

  At baseline

Study Arms (2)

Patients with Schizophrenia

Antipsychotic-free patients with schizophrenia or schizophreniform disorder

Radiation: PET Scan

Healthy Controls

Healthy controls matched for age, sex, cannabis, and nicotine consumption to the 29 patients

Radiation: PET Scan

Interventions

PET Scan RADIATION

PET scan using the novel \[11C\]MK-6884 tracer to measure M4R during the antipsychotic-free state

Healthy Controls; Patients with Schizophrenia

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

Antipsychotic-free patients with schizophrenia or schizophreniform disorder and healthy controls

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T1R8, Canada

Location

Related Links

• 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.

Biospecimen

Retention: SAMPLES WITH DNA

arterial blood sample

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

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: SPONSOR

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: February 26, 2024
• Study Start: March 11, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)