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

Phase 2Enrolling By InvitationNCT04786223

Val Lowe125 enrolled

Overview

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 as looking to learn more about the side effects of a new radioactive tracer (radiotracer) C-11 ER176.

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 dementia with Lewy bodies (DLB) individuals with biomarker-identified brain pathology to help address these gaps in knowledge in the field.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

125

Conditions

Alzheimer Disease Lewy Body's Dementia

Interventions

C-11 ER-176DRUG

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.

Blood TestDIAGNOSTIC_TEST

Participants will undergo a one time venipuncture blood collection to evaluate the presence of inflammatory and genetic markers.

Eligibility

Sex: ALLMin age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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+, 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.

Locations (1)

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 4 years

Determine if neuroinflammation, as measured by PET imaging, is associated with plasma biomarkers of inflammation or other neurologic diseases.

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.

Time frame: 4 years

Secondary Outcomes

Incidence of adverse events attributable to ER176.

Data from ClinicalTrials.gov

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