M1 Schizophrenia PET Study

Healthy Clinical Trial

Official title:

Muscarinic M1 Receptor Availability and Cognition in Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05105542
• Other study ID #: 2000031171
• Secondary ID: 1R21MH123870-01A
• Status: Completed
• Phase: Phase 2
• Start date: April 20, 2021
• Est. completion date: October 31, 2023

Study information

• Verified date: March 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

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.

Locations

Country	Name	City	State
United States	Connecticut Mental Health Center	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (58)

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* Note: There are 58 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hippocampal M1 availability	Measured by [11C]EMO availability (BPND)	10 days
Secondary	evoked ? oscillations	Measured by EEG	10 days
Secondary	verbal memory	Measured by cognitive assessments	10 days