Back to resultsTargeting Neuroinflammation as a Contributing Pathology in Alzheimer's Disease Dementia
Primary Purpose
Alzheimer Disease
Status
Enrolling by invitation
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
C-11 ER-176
Blood Test
Sponsored by
About this trial
This is an interventional diagnostic trial for Alzheimer Disease
Eligibility Criteria
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.
Sites / Locations
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
C-11 ER176 PET/CT
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04786223
Brief Title
Targeting Neuroinflammation as a Contributing Pathology in Alzheimer's Disease Dementia
Official Title
Targeting Neuroinflammation as a Contributing Pathology in Alzheimer's Disease Dementia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
March 30, 2021 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Val Lowe
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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. Additionally, researchers as looking to learn more about the side effects of a new radioactive tracer (radiotracer) C-11 ER176.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Alzheimer's Disease Dementia
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
C-11 ER176 PET/CT
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
C-11 ER-176
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
Blood Test
Intervention Description
Participants will undergo a one time venipuncture blood collection to evaluate the presence of inflammatory and genetic markers.
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
4 year
Title
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.).
Description
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.
Time Frame
4 year
Title
Determine if neuroinflammation, as measured by PET imaging, is associated with plasma biomarkers of inflammation.
Description
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 year
Secondary Outcome Measure Information:
Title
Incidence of adverse events attributable to ER176.
Description
Adverse events related to ER176 will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0)
Time Frame
4 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Val Lowe, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Targeting Neuroinflammation as a Contributing Pathology in Alzheimer's Disease Dementia
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