Measuring Brain Amyloid Plaque Load in Older Adults Using BAY 94-9172

Study Overview
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Brief Summary
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The overall goal of this project is to establish and validate biomarkers associated with the risk and progression of late onset Alzheimer's disease, mild cognitive impairment and cognitive decline. The investigators will use baseline and longitudinal measurements of plasma amyloid beta-40 and amyloid beta-42 to investigate the risk of developing mild cognitive impairment and late onset Alzheimer's disease, as well as the rates of cognitive decline and Alzheimer's disease progression. Participants will be selected on the basis of change in plasma amyloid beta levels over prior assessment intervals. The purpose of the study is to examine whether brain amyloid plaque load, which will be measured with positron emission tomography and x-ray computed tomography brain imaging using Florbetaben from Bayer, varies as a function of change in plasma levels of amyloid beta. The driving hypothesis of the study is that high plasma levels of amyloid beta are an antecedent indicator of increased risk of cognitive decline, mild cognitive impairment, and incident late onset Alzheimer's disease, and that declining plasma levels of amyloid beta are associated with the onset of cognitive decline. Further, high plasma levels of amyloid beta are related to increased levels of amyloid beta in the brain as measured by positron emission tomography positivity, and the specific pattern of positron emission tomography positivity and a decline in plasma amyloid beta over time are associated with the onset of cognitive decline associated with late onset Alzheimer's disease.

Detailed Description
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This project is a sub-study of the Washington Heights-Inwood Community Aging Project, which is a multidisciplinary, epidemiological study of Alzheimer's disease and related neurodegenerative disorders. We will obtain positron emission tomography scans and simultaneous x-ray computed tomography scans using Florbetaben from Bayer on a selection of ongoing participants who will be selected on the basis of change in plasma levels of amyloid beta over time. Approximately 200 participants will receive scans beginning in 2009 and in the 2010-2012 assessment wave and then again in a 2014-2015 assessment wave. Our intention is to examine whether uptake of Florbetaben in the brain varies as a function of previous history of change in plasma levels of amyloid beta in order to validate plasma amyloid beta as a viable biomarker for late onset Alzheimer's disease.

Official Title
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BAY 94-9172 PET/CT in Cognitively Normal Older Adults, Older Adults With Mild Cognitive Impairment, and Older Adults With Alzheimer's Disease

Conditions
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Late Onset Alzheimer Disease

Intervention / Treatment
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* Drug: BAY 94-9172 (Florbetaben)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current Washington Heights-Inwood Community Aging Project (WHICAP) participant Age 65 or older Residing in the community of Washington-Heights/Inwood/Hamilton Heights Is able to provide informed consent, understand the information provided on the purpose and conduct of the trial and exhibits adequate visual, auditory and communication capabilities to enable compliance with study procedures. This includes performing the psychometric testing and being able to lie down flat in the Positron Emission Tomography (PET) scanner Possesses a general health that permits adequate compliance with all study procedures. Informed consent has been signed and dated (with time) by the subject and/or the subject's caregiver (for probable Alzheimer's Disease (AD) patients) Exclusion Criteria: Has any contraindication to PET, such as claustrophobia, or inability to lie flat for half an hour as determined by the onsite radiologist performing the scan Current, past, or anticipated exposure to radiation, which may include being badged for radiation exposure in the workplace or participation in nuclear medicine procedures, including research protocols in the last year Significant active physical illness particularly those that may affect the brain including blood dyscrasias, lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, autonomic neuropathies, peripheral vascular disease, low hemoglobin and malignancy Scheduled for surgery and/or another invasive procedure within the time period of up to 24 hours following scan Allergic to the tracer or any of its constituents and/or has a history of severe allergic reactions to drugs or allergens (e.g. patients with allergic asthma) Critically ill and/or medically unstable and whose clinical course within the observation period is unpredictable, e.g. participants with 14 days of myocardial infarction or stroke, unstable participants with previous surgery (within 7 days), participants with advanced heart insufficiency (New York Heart Association (NYHA) stage IV), or participants with acute renal failure. Has received any contrast material (X-ray, Magnetic Resonance Imaging (MRI)), or radiopharmaceuticals within 48 hours prior to the application of the Investigational Medicinal Product (IMP) or for whom application of such a substance is planned for 24 hours following IMP administration

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY 94-9172<br>BAY 94-9172 PET/CT | Drug: BAY 94-9172 (Florbetaben)<br>* Measure of brain amyloid load using BAY 94-9172 PET/CT<br>* Other names: Bay 91-9172;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in amyloid plaque load in the brain of the course of 3 years | Positron emission tomography (PET) and x-ray computed tomography (CT) brain imaging using Florbetaben is considered an in vivo measure of brain amyloid plaque load. We will obtain PET/CT scans on a selection of participants who will be selected on the basis of change in plasma levels of amyloid beta to validate amyloid beta as a viable biomarker for late onset Alzheimer's disease. Participants will receive scans in a 2010-2012 assessment wave, and then again in a 2014-2015 assessment wave to determine whether increased uptake in the brain correlates with declining levels of plasma amyloid beta | Amyloid plaque load in the brain will be measured at baseline and again 3 years later | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, Positron emission tomography, Biomarker, Plasma Aβ, Brain amyloid plaque load