M1 Schizophrenia PET Study

Sponsor

Yale University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05105542

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arm

23.4

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Schizoaffective Disorder Healthy	Drug: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Diagnostic

Official Title:

Muscarinic M1 Receptor Availability and Cognition in Schizophrenia

Actual Study Start Date :

Apr 20, 2021

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 11C-EMO - A Novel PET Radiotracer for Muscarinic M1 Receptor Participants will undergo a single PET scan with [11C]EMO ≤ 20 mCi	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. Other Names: PET Scan

Arm

Intervention/Treatment

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

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

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.

Other Names:

PET Scan

Outcome Measures

Primary Outcome Measures

Hippocampal M1 availability [10 days]
Measured by [11C]EMO availability (BPND)

Secondary Outcome Measures

evoked ɣ oscillations [10 days]
Measured by EEG
verbal memory [10 days]
Measured by cognitive assessments

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Men and women aged 18- 55 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
Smokers who are unable to abstain from cigarette use for 5 days
People who suffer from claustrophobia, have MRI incompatible implants, or other contraindications for MRI and PET scans