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

NCT04786223 | Enrolling By Invitation Phase 2 DMC FDA Drug

• 1 other identifier: 20-000866
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lewy Body's Dementia; Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• 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 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.

  4 years

Secondary Outcomes (1)

• Incidence of adverse events attributable to ER176.

  4 year

Study Arms (1)

C-11 ER176 PET/CT

OTHER

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; Diagnostic Test: Blood Test

Interventions

C-11 ER-176 DRUG

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.

C-11 ER176 PET/CT

Blood Test DIAGNOSTIC_TEST

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

C-11 ER176 PET/CT

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Val Lowe: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Val Lowe, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Alzheimer's Disease Dementia, dementia with Lewy bodies

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: March 8, 2021
• Study Start: March 30, 2021
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 3, 2026

Record last verified: 2026-02

Locations

US (1)