Imaging Inflammation in Alzheimer's Disease With 11C-ER176

Study Overview
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Brief Summary
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This study is being done to learn about inflammation in the brain of those with Alzheimer's disease (AD). The purpose of this study is to determine if 11C-ER176 is able to accurately measure inflammation in patients with Alzheimer's disease. Both patients (with either mild cognitive impairment (MCI) or Alzheimer's disease) and healthy controls (participants without memory complaints or impairment) will be included in this study.

Detailed Description
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Inflammation likely plays a role in the damage to the brain caused by Alzheimer's disease. Accurately measuring inflammation in the brain could provide new information about the mechanisms that cause Alzheimer's disease, and could help identify new treatments that reduce inflammation. Positron emission tomography (PET) imaging is a type of brain scanning method that allows investigators to measure small molecules in the brain. ER176-PET was recently developed as an improved method for measuring brain inflammation. However, ER176-PET has not yet been used in patients with Alzheimer's disease. The investigators propose to use ER176-PET imaging in subjects with mild cognitive impairment (a very early stage of Alzheimer's disease) or mild Alzheimer's disease to compare the amount of inflammation with that seen in older control subjects. The investigators will first use a gold standard method of measuring ER176 in brain that requires sampling arterial blood during the scan. The investigators will compare these results to those obtained using novel methods that don't require blood sampling. The investigators hope to show that ER176 is a useful tool for measuring inflammation in Alzheimer's disease, and that the investigators can develop a way to obtain ER176 PET scans that don't require arterial blood sampling. This study uses a special type of scan called a PET scan to take pictures of the brain. During the PET scan, a special dye is injected into the body. Two types of dye will be used in this study: Florbetaben and 11C-ER176. Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease. Florbetaben has been approved by the Food and Drug Administration to help diagnose Alzheimer's disease. 11C-ER176 sticks to parts of the brain where there is inflammation. Past studies have shown that inflammation is present in the brains of patients with Alzheimer's disease.

Official Title
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Imaging Inflammation in Alzheimer's Disease With 11C-ER176

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: 11C-ER176
* Drug: Florbetaben


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50 and older Meet criteria for either a) amnestic mild cognitive impairment or Alzheimer's disease, or b) have no cognitive impairment If you are unable to provide informed consent, you must have a surrogate decision maker and be able to verbally assent to the study procedures Written and oral fluency in English Able to participate in all scheduled evaluations and to complete all required tests and procedures. In the opinion of the investigator, you must be considered likely to comply with the study protocol and to have a high probability of completing the study. Exclusion Criteria: Past or present history of certain brain disorders other than MCI or AD. Certain significant medical conditions, which make study procedures of the current study unsafe. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries. Contraindication to MRI scanning Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.). Exposure to research related radiation in the past year that, when combined with this study, would place you above the allowable limits. Participation in the last year in a clinical trial for a disease modifying drug for AD. Inability to have a catheter in your vein for the injection of radioligand. Inability to have blood drawn from your veins. Taking anticoagulant medication (e.g., warfarin).

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive impairment<br>Alzheimer's disease (mild cognitive impairment or mild stage Alzheimer's disease dementia) | Drug: 11C-ER176<br>* 11C-ER176 sticks to parts of the brain where there is inflammation. Past studies have shown that inflammation is present in the brains of patients with Alzheimer's disease. The purpose of this study is to determine if 11C-ER176 is able to accurately measure inflammation in patients with Alzheimer's disease.<br>* Other names: [11C] ER176;Drug: Florbetaben<br>* Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease.<br>* Other names: NeuraCeq;|
| Active Comparator: No cognitive impairment<br>Healthy Controls | Drug: 11C-ER176<br>* 11C-ER176 sticks to parts of the brain where there is inflammation. Past studies have shown that inflammation is present in the brains of patients with Alzheimer's disease. The purpose of this study is to determine if 11C-ER176 is able to accurately measure inflammation in patients with Alzheimer's disease.<br>* Other names: [11C] ER176;Drug: Florbetaben<br>* Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease.<br>* Other names: NeuraCeq;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 11C-ER176 Total Distribution Volume | Total distribution volume reflects the amount of TSPO (the inflammatory protein that 11C-ER176 sticks to) in the brain. This measure requires arterial blood sampling. | Up to one year from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 11C-ER176 Standardized Uptake Value Ratio | The standardize uptake value ratio is the concentration of radioactivity measured from the 11C-ER176 positron emission tomography (PET) scan in the cortex compared to the uptake in the cerebellum (pseudo-reference region). This is a simplified quantification technique compared to the Total Distribution Volume, but is linearly related to it. Higher values indicate more neuroinflammation. | Up to one year from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET scans, Inflammation