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Imaging Inflammation in Alzheimer's Disease

Primary Purpose

Alzheimer's Disease

Status

Enrolling by invitation

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

11C-PBR28

18F-Florbetaben

Lumbar puncture (optional)

About this trial

This is an interventional diagnostic trial for Alzheimer's Disease focused on measuring inflammation, aging, mild cognitive impairment

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

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.
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.

Sites / Locations

Columbia University irving Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cognitive impairment

No cognitive impairment

Arm Description

Alzheimer's disease, Preclinical Alzheimer's disease or Impairment due to suspected non-Alzheimer's disease pathophysiology

Normal aging

Outcomes

Primary Outcome Measures

11C-PBR28 binding (standardized uptake value ratio)

In vivo quantification radioligand binding to TSPO expression on microglia in the brain.

Secondary Outcome Measures

18F-Florbetaben binding (standardized uptake value ratio)

In vivo quantification of radioligand binding to Amyloid-Beta protein in the brain.

Cerebral spinal fluid (CSF) biomarkers

Protein analysis of cerebral spinal fluid.

Full Information

NCT ID

NCT02831283

First Posted

July 10, 2016

Last Updated

September 16, 2022

Sponsor

James M Noble, MD, MS, CPH, FAAN

Collaborators

National Institute on Aging (NIA)

1. Study Identification

Unique Protocol Identification Number

NCT02831283

Brief Title

Imaging Inflammation in Alzheimer's Disease

Official Title

Imaging Inflammation in Elders With Different Clinical and Biomarker Profiles of Alzheimer's Disease

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Enrolling by invitation

Study Start Date

June 2016 (undefined)

Primary Completion Date

June 2023 (Anticipated)

Study Completion Date

June 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

James M Noble, MD, MS, CPH, FAAN

Collaborators

National Institute on Aging (NIA)

4. Oversight

Data Monitoring Committee

5. Study Description

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.

Detailed Description

This study is being done to determine the relationship between inflammation, cognitive impairment, and amyloid burden in elderly subjects with different clinical and biomarker profiles of Alzheimer's disease (AD). Participants will undergo amyloid PET imaging with 18F-Florbetaben with target number of completers being 15 amyloid-positive elders with impairment, 15 amyloid-positive elders with normal cognition, 15 amyloid-negative elders with impairment, and 15 amyloid-negative elders with normal cognition. Subjects will undergo screen that includes neuropsychological testing, brain MRI, and PET imaging with 18F-florbetaben to define the above 4 groups. Subjects will have 11C-PBR28 PET imaging to measure the 18 kDa translocator protein (a marker of inflammation). Subjects will have the option to have lumbar puncture performed to measure CSF concentrations of amyloid,tau, phospho-tau, and inflammatory markers.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer's Disease

Keywords

inflammation, aging, mild cognitive impairment

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cognitive impairment

Arm Type

Experimental

Arm Description

Alzheimer's disease, Preclinical Alzheimer's disease or Impairment due to suspected non-Alzheimer's disease pathophysiology

Arm Title

No cognitive impairment

Arm Type

Active Comparator

Arm Description

Normal aging

Intervention Type

Drug

Intervention Name(s)

11C-PBR28

Other Intervention Name(s)

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

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

18F-Florbetaben

Other Intervention Name(s)

Neuraceq

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Lumbar puncture (optional)

Other Intervention Name(s)

Intervention Description

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

Primary Outcome Measure Information:

Title

11C-PBR28 binding (standardized uptake value ratio)

Description

In vivo quantification radioligand binding to TSPO expression on microglia in the brain.

Time Frame

Up to 1 year from screening

Secondary Outcome Measure Information:

Title

18F-Florbetaben binding (standardized uptake value ratio)

Description

In vivo quantification of radioligand binding to Amyloid-Beta protein in the brain.

Time Frame

Up to 1 year from screening

Title

Cerebral spinal fluid (CSF) biomarkers

Description

Protein analysis of cerebral spinal fluid.

Time Frame

Up to 1 year from screening

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James M. Noble, MD, MS

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University irving Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

33646153

Citation

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.

Results Reference

derived

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Imaging Inflammation in Alzheimer's Disease

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