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

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

Study Overview

• Status: Enrolling by invitation
• Conditions: Lewy Body Dementia (LBD); Alzheimer Dementia (AD)
• Intervention / Treatment: Diagnostic test: Blood Test; Drug: C-11 ER-176

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, mildly impaired, AD dementia, and mild cognitively impaired and dementia with Lewy bodies (DLB) individuals with biomarker-identified brain pathology to help address these gaps in knowledge in the field.

• Study Type: Interventional
• Enrollment (Estimated): 125
• 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: Yes

Description

Inclusion Criteria:

• Males or females 60 years of age or older.
• Meet the requirements for one of the five groups (CU A-, CU A+, MCI A+, AD A+, MCI-LB or DLB).
• Neurologic evaluation procedures with testing in the MCSA, ADRC, Longitudinal Imaging Biomarkers of Prodromal and Overt DLB studies or Mayo Clinic Behavioral Neurology Practice. Must have had or plan to have at least 2 testing sessions.
• All participants must have or plan to have an amyloid PiB PET scan and MRI brain scan within approximately 6 months of the first ER176 PET/CT scan. Participants undergoing an optional additional ER176 scan are preferred, but not required, to have or plan to have an amyloid PiB PET scan and MRI brain scan within approximately 6 months of the second ER176 PET/CT scan.
• 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.

Diagnostic test: Blood Test; Participants will undergo a one time venipuncture blood collection to evaluate the presence of inflammatory and genetic markers.; Drug: C-11 ER-176; Participants will receive a one-time administration of C-11 ER176 and undergo a PET/CT imaging study. Participants may be invited to return for an additional administration of C-11 ER176 and undergo an additional PET/CT imaging study.

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. We note that similar patterns may also be observed in other neurodegenerative diseases such as DLB, particularly in cases with mixed AD pathology.	4 years
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, as well as in DLB 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 years
Determine if neuroinflammation, as measured by PET imaging, is associated with blood and/or CSF biomarkers of inflammation or other neurologic diseases and related blood tests.	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 blood and/or CSF 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 plasma biomarkers of inflammation and other neurologic diseases and related blood tests (cytokines, TSPO, amyloid and tau) will correlate with increased PET neuroinflammation imaging signal.	4 years

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, 2029
• Study Completion (Estimated): March 1, 2030

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): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Neuroinflammation; ER176
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Inflammation; Dementia; Tauopathies; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Pathological Conditions, Signs and Symptoms; Neuroinflammatory Diseases; Alzheimer Disease; Lewy Body Disease; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests
• 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
• product manufactured in and exported from the U.S.: No