Longitudinal Imaging of Microglial Activation in Different Clinical Variants of Alzheimer's Disease

NCT04576793 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: AAAS7810R01AG063888
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine how inflammation is related to other changes in the brain that occur during the progression of Alzheimer's disease. The investigators are also studying how inflammation is related to the symptoms that first occur in patients with Alzheimer's disease (AD). For this reason, the investigators are asking people with different versions of Alzheimer's disease and/or other related dementias to participate. This includes patients with:

• Mild Cognitive Impairment
• Posterior cortical atrophy - a version of Alzheimer's disease with vision difficulties
• Logopenic variant primary progressive aphasia - a version of Alzheimer's disease with language difficulties
• Amnestic Alzheimer's disease - a "typical" version of Alzheimer's disease with memory difficulties
• The investigators are also enrolling older adults with normal visual, language, and memory function.

Conditions

Alzheimer Disease

Keywords

Inflammation; PET scans; Cognitive Impairment; Posterior Cortical Atrophy; Logopenic Variant Primary Progressive Aphasia; Amnestic Alzheimer's Disease; MK-6240; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (2)

• 11C-ER176 Standardized Uptake Value Ratio

  The standardize uptake value ratio is the concentration of radioactivity measured from the 11C-ER176 PET scan in the cortex compared to the uptake in the cerebellum (pseudo-reference region).

  Up to 24 months

• 18F-MK6240 Standardized Uptake Value Ratio

  The standardize uptake value ratio is the concentration of radioactivity measured from the 18F-MK6240 PET scan in the cortex compared to the uptake in the cerebellum (pseudo-reference region).

  Up to 24 months

Study Arms (2)

Cognitive impairment

EXPERIMENTAL

* Mild Cognitive Impairment * Posterior cortical atrophy - a version of Alzheimer's disease with vision difficulties * Logopenic variant primary progressive aphasia - a version of Alzheimer's disease with language difficulties * Amnestic Alzheimer's disease - a "typical" version of Alzheimer's disease with memory difficulties

Drug: 11C-ER176; Drug: 18F-MK6240; Drug: 18F-Florbetaben; Procedure: Lumbar Puncture

No cognitive impairment

ACTIVE COMPARATOR

Healthy controls

Drug: 11C-ER176; Drug: 18F-MK6240; Drug: 18F-Florbetaben; Procedure: Lumbar Puncture

Interventions

11C-ER176 DRUG

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. 11C-ER176 will be administered at activity up to 20 millicurie (mCi) per injection.

Also known as: [11C] ER176

Cognitive impairment; No cognitive impairment

18F-MK6240 DRUG

MK-6240 measures a protein called in the brain. MK-6240 is experimental but has been used in several human studies before and has been proven to accurately measure tau in the brain.

Also known as: [18F-MK6240]

Cognitive impairment; No cognitive impairment

18F-Florbetaben DRUG

Florbetaben has been approved by the FDA to help diagnose Alzheimer's disease. florbetaben measures amyloid in the brain.

Also known as: [18F] Florbetaben

Cognitive impairment; No cognitive impairment

Lumbar Puncture PROCEDURE

Inflammation can also be measured by looking at certain proteins in the spinal fluid. In order to measure these proteins in the spinal fluid, the investigators will perform a lumbar puncture (spinal tap).

Also known as: Spinal Tap

Cognitive impairment; No cognitive impairment

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 50 and over at time of screening.
• At screening, must have no cognitive impairment, or meet criteria for amnestic Alzheimer's disease, posterior cortical atrophy, or logopenic variant primary progressive aphasia. Diagnoses will be made based on history, exam, neuropsychological testing, brain MRI, and consensus diagnosis.
• Patients must have Clinical Dementia Rating scale score of 0.5 or 1 at enrollment. Controls must have Clinical Dementia Rating scale score of 0 at enrollment.
• Subjects unable to provide informed consent must have a surrogate decision maker.
• Written and oral fluency in English or Spanish.
• Able to participate in all scheduled evaluations and to complete all required tests and procedures.
• In the opinion of the PI, the subject must be considered likely to comply with the study protocol and to have a high probability of completing the study.

You may not qualify if:

• Past or present history of a brain disorder other than Alzheimer's disease (including presence of cortical infarct on MRI even in absence of clinical stroke).
• Serious 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 subjects above the allowable limits.

Sponsors & Collaborators

• Patrick Lao: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Inflammation; Cognitive Dysfunction

Interventions

4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene; Spinal Puncture

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Patrick J. Lao, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Smith

CONTACT

212-305-9079; as6545@cumc.columbia.edu

Diana S. Guzman

CONTACT

212-305-9079; dsg2158@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 6, 2020
• Study Start: November 17, 2020
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: Up to two weeks after review and approval of request.
• Access Criteria: Investigator qualifications and previous work will be reviewed by PI. Subsequent email correspondence will relay technical criteria needed for access.

Locations

US (1)