M1 Schizophrenia PET Study

Yale University

Status and phase: Completed; Phase 1

Conditions: Healthy; Schizophrenia; Schizoaffective Disorder

Treatments: Drug: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor; Device: PET Scan

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05105542

2000031171

1R21MH123870-01A1 (U.S. NIH Grant/Contract)

1R01MH113557-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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18 participants in 2 patient groups

Schizophrenia or schizoaffective disorder

Experimental group

Description:

Participants will undergo a single PET scan with \[11C\]EMO ≤ 20 mCi

Treatment:

Device: PET Scan

Drug: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor

Healthy Controls

Experimental group

Description:

Participants will undergo a single PET scan with \[11C\]EMO ≤ 20 mCi

Treatment:

Device: PET Scan

Drug: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor