Clinical trial NCT05105542: M1 Schizophrenia PET Study
Official title: Muscarinic M1 Receptor Availability and Cognition in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Schizoaffective Disorder
Healthy
Keywords: Schizophrenia
Muscarinic M1 Receptor
M1 AChR
[11C]EMO
PET Scan
MRI Scan
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2021-11-03
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Hippocampal M1 availability
timeFrame: 10 days
Secondary outcomes:
measure: evoked ɣ oscillations
timeFrame: 10 days
measure: verbal memory
timeFrame: 10 days
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Connecticut Mental Health Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Rajiv Radhakrishnan, MD
role: PRINCIPAL_INVESTIGATOR
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