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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: 11C-ER176; Drug: Florbetaben

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age 50 and older
2. Meet criteria for either a) amnestic mild cognitive impairment or Alzheimer's disease, or b) have no cognitive impairment
3. 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
4. Written and oral fluency in English
5. Able to participate in all scheduled evaluations and to complete all required tests and procedures.
6. 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:

1. Past or present history of certain brain disorders other than MCI or AD.
2. Certain significant medical conditions, which make study procedures of the current study unsafe. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries.
3. Contraindication to MRI scanning
4. Conditions precluding entry into the scanners (e.g. morbid obesity, claustrophobia, etc.).
5. Exposure to research related radiation in the past year that, when combined with this study, would place you above the allowable limits.
6. Participation in the last year in a clinical trial for a disease modifying drug for AD.
7. Inability to have a catheter in your vein for the injection of radioligand.
8. Inability to have blood drawn from your veins.
9. Taking anticoagulant medication (e.g., warfarin).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cognitive impairment; Alzheimer's disease (mild cognitive impairment or mild stage Alzheimer's disease dementia)	Drug: 11C-ER176; 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.; Other Names: [11C] ER176; Drug: Florbetaben; Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease.; Other Names: NeuraCeq
Active Comparator: No cognitive impairment; Healthy Controls	Drug: 11C-ER176; 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.; Other Names: [11C] ER176; Drug: Florbetaben; Florbetaben sticks to amyloid plaques, which are in the brain in Alzheimer's disease.; Other Names: NeuraCeq

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Patrick Lao, PhD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2018
• Primary Completion (Actual): July 20, 2022
• Study Completion (Actual): July 20, 2022

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 16, 2018

Study Record Updates

• Last Update Posted (Actual): April 17, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; PET scans
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Inflammation
• Other Study ID Numbers: AAAR6570

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be available upon reasonable request from a qualified investigator.
• IPD Sharing Time Frame: Up to two weeks after review and approval of request.
• IPD Sharing Access Criteria: Investigator qualifications and previous work will be reviewed by PI. Subsequent email correspondence will relay technical criteria needed for access.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No