Investigation of Inflammation in Alzheimer's Disease and Related Dementias (ADRD) Using [11C]-CS1P1

Study Overview
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Brief Summary
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This study involves a brain positron emission tomography (PET) scan with a new, investigational radioactive tracer called [11C]-CS1P1 to identify inflammation in the brain. The primary objective of this IND study is to further evaluate the [11C]-CS1P1 for PET imaging of S1P1 expression in healthy older adults and in adults with Alzheimer's disease and Related Dementia (ADRD). Investigators will complete imaging of the brain and neck in older adults with normal cognition and those with clinically diagnosed cognitive impairment from ADRD to characterize [11C]-CS1P1 uptake in the brain. Investigators will compare the normal cognition participants to patients with ADRD to collect preliminary data that will subsequently test the hypothesis that [11C]-CS1P1 uptake is elevated in patients with ADRD.

Official Title
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Investigation of Inflammation in Alzheimer's Disease and Related Dementias (ADRD) Using [11C]-CS1P1

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: [11C]-CS1P1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, any race; Age ≥ 50 years; Capable of providing written informed consent OR having a legally authorized representative (LAR) to provide informed consent for volunteering to undergo research procedure; Additional inclusion for ADRD group: clinical diagnosis of mild cognitive impairment or early dementia due to ADRD, OR biomarker diagnosis of Alzheimer's disease, with or without symptoms. Exclusion Criteria: Hypersensitivity to [11C]-CS1P1 or any of its excipients; Contraindications to PET, CT, or MRI (e.g. certain incompatible electronic medical devices, inability to lie still for extended periods) that make it potentially unsafe for the individual to participate; Severe claustrophobia; Women who are currently pregnant or breast-feeding; Currently undergoing radiation therapy; Any condition that, in the opinion of the Sponsor-Investigator or designee could increase risk to the participant, limit the participant's ability to tolerate the research procedures or interfere with collection of the data (e.g., renal or liver failure, advanced cancer); Participants who in the last 6 months experienced any of the following cardiovascular conditions or findings in the screening electrocardiogram (ECG): clinically significant cardiac arrhythmias including high grade heart block (type 2 or greater), unstable angina, or decompensated heart failure requiring hospitalization or Class III/IV heart failure; Moderate to Severe anemia with Hemoglobin < than 9.9 in both males and females. Current or recent (within 12 months prior to screening) participation in research studies involving radioactive agents such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.1. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?FR=361.1

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy participants<br> | Drug: [11C]-CS1P1<br>* Participants will receive a single intravenous bolus injection of 12.0 - 17.0 milliCurie (mCi) of the investigational radiotracer [11C]-CS1P1. Participants will then undergo a brain [11C]-CS1P1 PET scan<br>|
| Participants with cognitive impairment (Alzheimer's disease)<br> | Drug: [11C]-CS1P1<br>* Participants will receive a single intravenous bolus injection of 12.0 - 17.0 milliCurie (mCi) of the investigational radiotracer [11C]-CS1P1. Participants will then undergo a brain [11C]-CS1P1 PET scan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET imaging studies of [11C]-CS1P1 in healthy control participants and participants with Alzheimer's Disease and measuring the uptake of [11C]-CS1P1 tracer. | To test the hypothesis that specific binding of [11C]-CS1P1 is elevated in participants with ADRD compared to healthy normal control participants. | Through study completion, an average of 1 year |