M1 Schizophrenia PET Study

Study Overview
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Brief Summary
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This exploratory study seeks to examine M1 receptor availability in SZ patients and to relate M1 receptor availability to proximal and distal measures of cognitive performance, namely evoked ɣ oscillations in the EEG and verbal memory. Furthermore, the relationship between hippocampal [11C]EMO availability (BPND), evoked ɣ oscillations, verbal memory, and measures of illness severity will be explored.

Detailed Description
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Converging lines of evidence from postmortem studies provide strong evidence that brain muscarinic M1 receptor deficit is present in a subset of schizophrenia (SZ) patients. M1 receptors are an important target for cognitive deficits in SZ. However, until now, it has not been possible to examine the heterogeneity of SZ with respect to M1 receptor availability in vivo. The development of a novel positron emission tomography (PET) ligand, [11C]EMO, at Yale PET Center provides a unique opportunity to, for the first time, examine in vivo brain muscarinic M1 receptor availability in SZ and, concurrently, elucidate the relationship of M1 receptors to cognitive deficits in SZ. The investigators will compare M1 receptor availability in SZ patients and age-, gender-matched healthy controls using [11C]EMO and the High Resolution Research Tomograph (HRRT), a PET scanner with high sensitivity and resolution available for human brain imaging. This study will explore the relationship between: hippocampal [11C]EMO binding (as a measure of hippocampal M1 AChR availability), encoding-related γ power during a verbal memory task, verbal memory, gender, and serum acetylcholine level. This exploratory study will provide the necessary pilot data to conduct a larger study to fully investigate the heterogeneity of SZ with respect to M1 receptor availability.

Official Title
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Muscarinic M1 Receptor Availability and Cognition in Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorder, Healthy

Intervention / Treatment
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* Drug: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18- 65 years that are physically and mentally healthy with the exception of DSM-5 schizophrenia or schizoaffective disorder diagnosis Subjects with no metal in the body that may pose a risk during MRI scanning No significant medical history, including head trauma and bleeding disorders Exclusion Criteria: Men and women with a history or presence of clinically significant medical conditions People who suffer from claustrophobia, have MRI incompatible implants, or other contraindications for MRI and PET scans

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Two groups will be studied: 1.) patients diagnosed with schizophrenia or schizoaffective disorder, and 2.) age and gender-matched healthy controls. Both groups will undergo neuroimaging, cognitive assessments, etc.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor<br>Participants will undergo a single PET scan with [11C]EMO ≤ 20 mCi | Drug: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor<br>* The radiotracer, [11C]EMO, will be administered at the beginning of each PET scan.<br>* Other names: PET Scan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hippocampal M1 availability | Measured by [11C]EMO availability (BPND) | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evoked ɣ oscillations | Measured by EEG | 10 days | 
| verbal memory | Measured by cognitive assessments | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Muscarinic M1 Receptor, M1 AChR, [11C]EMO, PET Scan, MRI Scan