Imaging Inflammation in Alzheimer's Disease

NCT02831283 | Completed Phase 2 Results

• 2 other identifiers: AAAO11511K23AG052633-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to learn about inflammation and amyloid in Alzheimer's disease. A type of brain scan called a PET scan is used measure 1) inflammation and 2) abnormal accumulation of a the amount of a certain protein fragment called beta-amyloid (plaques) in the brain. These are thought to be involved in Alzheimer's disease. The investigators will also perform brain MRI and do tests to measure the participants' memory and thinking.

Conditions

Alzheimer's Disease

Keywords

inflammation; aging; mild cognitive impairment

Outcome Measures

Primary Outcomes (1)

• 11C-PBR28 Binding

  In vivo quantification radioligand binding to TSPO expression on microglia in the brain, reported as standardized uptake value ratio (SUVR).

  Up to 1 year from screening

Secondary Outcomes (2)

• 18F-Florbetaben Binding

  Up to 1 year from screening

• Cerebral Spinal Fluid (CSF) Biomarkers

  Up to 1 year from screening

Study Arms (4)

Amyloid-positive with cognitive impairment (AD)

EXPERIMENTAL

Amyloid-positive patients who already have cognitive impairment at the time of enrollment.

Drug: 11C-PBR28; Drug: 18F-Florbetaben; Procedure: Lumbar puncture (optional)

Amyloid-positive without impairment (preclinical AD)

ACTIVE COMPARATOR

Cognitively normal subjects who are amyloid-positive

Drug: 11C-PBR28; Drug: 18F-Florbetaben; Procedure: Lumbar puncture (optional)

Amyloid-negative with cognitive impairment

ACTIVE COMPARATOR

Participants with cognitive impairment due to suspected non-AD pathophysiology

Drug: 11C-PBR28; Drug: 18F-Florbetaben; Procedure: Lumbar puncture (optional)

Amyloid-negative without impairment (normal aging)

ACTIVE COMPARATOR

Cognitively normal subjects who are amyloid-negative on PET, and lack signs of neurodegeneration from other biomarkers

Drug: 11C-PBR28; Drug: 18F-Florbetaben; Procedure: Lumbar puncture (optional)

Interventions

11C-PBR28 DRUG

11C-PBR28 is a PET radioligand that binds to the 18 kDa translocator protein (TSPO), a marker of inflammation. 11C-PBR28 has previously been administered in humans. 11C-PBR28 will be administered at activity of up to 20 mCi per injection.

Also known as: 11C-[O-methyl-11C]N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine

Amyloid-negative with cognitive impairment; Amyloid-negative without impairment (normal aging); Amyloid-positive with cognitive impairment (AD); Amyloid-positive without impairment (preclinical AD)

18F-Florbetaben DRUG

18F-Florbetaben (Neuraceq) has FDA approval for human use in evaluation of Alzheimer's disease. 18F-Florbetaben will be administered at activity up to 8.1 mCi per injection.

Also known as: Neuraceq

Amyloid-negative with cognitive impairment; Amyloid-negative without impairment (normal aging); Amyloid-positive with cognitive impairment (AD); Amyloid-positive without impairment (preclinical AD)

Lumbar puncture (optional) PROCEDURE

Subjects have the option to have lumbar puncture performed for the measurement of inflammatory markers in cerebrospinal fluid.

Also known as: LP

Amyloid-negative with cognitive impairment; Amyloid-negative without impairment (normal aging); Amyloid-positive with cognitive impairment (AD); Amyloid-positive without impairment (preclinical AD)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 60 and older.
• Meet criteria for either a) amnestic mild cognitive impairment (single or mixed domain) or mild Alzheimer's disease, or b) have no cognitive impairment based on history, exam, neuropsychological testing, and consensus diagnosis. MCI and mild AD patients must have Clinical Dementia Rating scale score of 0.5 or 1. Unimpaired subjects must have Clinical Dementia Rating scale score of 0.
• 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 investigator, 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 certain brain disorders other than MCI or AD.
• Certain significant medical conditions, which make study procedures of the current study unsafe.
• 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.
• Low affinity binding on TSPO genetic screen.
• Participation in the last year in a clinical trial for a disease modifying drug for AD.
• Inability to have a catheter in subject's vein for the injection of radioligand.
• Inability to have blood drawn from subject's veins.

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

Location

Related Publications (1)

• Klein J, Yan X, Johnson A, Tomljanovic Z, Zou J, Polly K, Honig LS, Brickman AM, Stern Y, Devanand DP, Lee S, Kreisl WC. Olfactory Impairment Is Related to Tau Pathology and Neuroinflammation in Alzheimer's Disease. J Alzheimers Dis. 2021;80(3):1051-1065. doi: 10.3233/JAD-201149.

  PMID: 33646153 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Inflammation; Cognitive Dysfunction

Interventions

(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; 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

Results Point of Contact

• Title: Patrick Lao
• Organization: Columbia University

PJL2133@CUMC.COLUMBIA.EDU

2123421351

Study Officials

• Patrick J Lao

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Assistant Professor of Neurology

Study Record Dates

• First Submitted: July 10, 2016
• First Posted: July 13, 2016
• Study Start: June 1, 2016
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: March 5, 2025
• Results First Posted: March 5, 2025

Record last verified: 2025-02

Locations

US (1)