NCT05105542

M1 Schizophrenia PET Study

Muscarinic M1 Receptor Availability and Cognition in Schizophrenia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

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.

Conditions

• Schizophrenia
• Schizoaffective Disorder
• Healthy

Interventions

Type	Name	Description
DRUG	11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor	The radiotracer, \[11C\]EMO, will be administered at the beginning of each PET scan.
DEVICE	PET Scan	PET scanner with high sensitivity and resolution available for human brain imaging

Timeline

• Start date: 2021-04-20
• Primary completion: 2023-10-31
• Completion: 2023-10-31
• First posted: 2021-11-03
• Last updated: 2024-11-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study