M1 Schizophrenia PET Study

Phase 1

Completed

• Conditions: Healthy; Schizophrenia; Schizoaffective Disorder
• Interventions: Drug: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor; Device: PET Scan

• Registration Number: NCT05105542
• Lead Sponsor: Yale University

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2021-04-20
• Study First Submitted: 2021-10-22
• Study First Submitted QC: 2021-10-22
• Study First Posted: 2021-11-03
• Primary Completion: 2023-10-31
• Study Completion: 2023-10-31
• Disposition First Posted: 2024-03-22
• Disposition First Submitted: 2024-10-18
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Schizophrenia or schizoaffective disorder	11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor	Participants will undergo a single PET scan with \[11C\]EMO ≤ 20 mCi
Schizophrenia or schizoaffective disorder	PET Scan	Participants will undergo a single PET scan with \[11C\]EMO ≤ 20 mCi
Healthy Controls	11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor	Participants will undergo a single PET scan with \[11C\]EMO ≤ 20 mCi
Healthy Controls	PET Scan	Participants will undergo a single PET scan with \[11C\]EMO ≤ 20 mCi

Primary Outcome Measures

Name	Time	Method
Hippocampal M1 availability	10 days	Measured by \[11C\]EMO availability (BPND)

Secondary Outcome Measures

Name	Time	Method
verbal memory	10 days	Measured by cognitive assessments
evoked ɣ oscillations	10 days	Measured by EEG

Trial Locations

Locations (1)

Connecticut Mental Health Center; 🇺🇸 New Haven, Connecticut, United States