Targeting Neuroinflammation as a Contributing Pathology in Alzheimer's Disease Dementia

This study is being done to research the usefulness of PET/CT imaging for measuring brain inflammation and its relation to Alzheimer's Disease. Additionally, researchers as looking to learn more about the side effects of a new radioactive tracer (radiotracer) C-11 ER176.

Study Overview

• Status: Enrolling by invitation
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: C-11 ER-176; Diagnostic test: Blood Test

Detailed Description

Alzheimer's disease (AD) dementia is a devastating illness with no cure. Treatments targeting known pathologic hallmarks of AD, such as amyloid-beta (AB), in symptomatic individuals have proved largely fruitless so other potential disease targets warrant exploration. Neuroinflammation has interesting possible associations with AD dementia and may contribute to AD dementia in different ways among different individuals. Previous PET neuroinflammation data are not entirely consistent and new methods of PET imaging and studies with larger cohorts are needed to further investigate the role of neuroinflammation in AD dementia and the utility of PET as a biomarker. This project seeks to test new PET neuroinflammation imaging methods in unimpaired and AD dementia individuals with biomarker-identified brain pathology to help address these gaps in knowledge in the field.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males or females 60 years of age or older.
• Meet the requirements for one of the four groups (CU A-, CU A+, MCI A+, AD A+).
• Undergoing neurologic evaluation procedures with cognitive testing in the MCSA or - ADRC for a minimum of about 3 years.
• All participants must have had an amyloid PiB PET scan and MRI brain scan within the previous 6 months.
• Capacity to sign consent or have a legally authorized representative to sign the consent.

Exclusion Criteria:

• Participants unable to lie down without moving for 20 minutes.
• Women who are pregnant or cannot stop breast feeding for 24 hours.
• Actively taking daily anti-inflammatory medications (NSAIDs, corticosteroids, etc.) except for a small control group.
• Generalized inflammatory condition and treatment with immunosuppressive, corticoid/glucocorticoid, steroidal or non-steroidal anti-inflammatory medication within 2 weeks of scanning (only acute medication use as an exclusion so as to limit medication interaction but preserve possible chronic systemic inflammation interaction).
• Standard safety exclusionary criteria for MRI such as metallic foreign bodies, pacemaker, etc., since the quantitative PET data analysis is based on anatomic criteria that are established uniquely for each subject by registration to his/her MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: C-11 ER176 PET/CT; C-11 ER176 is an investigational radiopharmaceutical that will be produced under cGMP in the Mayo Clinic Cyclotron Facility. The imaging agent (C-11 ER176) will be administered on an outpatient basis. It will be administered at a single time IV prior to the PET imaging.	Drug: C-11 ER-176; Participants will receive a one-time administration of C-11 ER176 and undergo a PET/CT imaging study. Blood samples for plasma biomarker testing will be obtained as part of the study.; Diagnostic test: Blood Test; Participants will undergo a one time venipuncture blood collection to evaluate the presence of inflammatory and genetic markers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if neuroinflammation, as measured by C-11 ER176 SUVr and inflammatory blood test measurements, is correlated with an increase in AB plaque, as measured by C-11 PiB SUVr.	Rationale: Biomarkers that are surrogates of AD pathology are needed to provide methods to select appropriate treatment strategies. We hypothesize that increased neuroinflammation PET signal is seen in AD A+ and MCI A+ as compared to CU A+ participants and is also increased in CU A+ vs. CU A- participants.	4 year
Determine if neuroinflammation, as measured by C-11 ER176 SUVr, is correlated with a history of increased cognitive decline in the 5 years preceding PET imaging, as measured by z scores from neuropsychiatric test results (memory, etc.).	Rationale: Surrogate biomarkers of AD pathology, beyond amyloid and tau, are needed to better assess disease progression and prognosis in AD dementia patients. We hypothesize that increased ER176 PET signal in amyloid positive participants is associated with the rate of cognitive decline preceding the neuroinflammation PET scan.	4 year
Determine if neuroinflammation, as measured by PET imaging, is associated with plasma biomarkers of inflammation.	Rationale: Plasma biomarkers are advantageous over imaging and CSF biomarkers with regards to cost, invasiveness, and feasibility in community settings. However, they may be less specific. We need to determine how plasma biomarkers correlate with PET neuroinflammation imaging as markers of disease progression, which markers are most highly correlated, and which may be specific to AD pathology. We hypothesize that hsCRP, IL-1B, IL-6, IL-8, IL-10, IL-13, G-CSF, IFN-g, and TNF-a will correlate with increased PET neuroinflammation imaging signal.	4 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events attributable to ER176.	Adverse events related to ER176 will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0)	4 year

Collaborators and Investigators

• Sponsor: Val Lowe
• Investigators: Principal Investigator: Val Lowe, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: March 3, 2021
• First Posted (Actual): March 8, 2021

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Inflammation; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease; Neuroinflammatory Diseases
• Other Study ID Numbers: 20-000866

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No