Imaging Inflammation in Alzheimer's Disease

Phase 2

Completed

Conditions: Alzheimer's Disease

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

Registration Number: NCT02831283

Lead Sponsor: Patrick Lao

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amyloid-negative without impairment (normal aging)	11C-PBR28	Cognitively normal subjects who are amyloid-negative on PET, and lack signs of neurodegeneration from other biomarkers
Amyloid-positive with cognitive impairment (AD)	11C-PBR28	Amyloid-positive patients who already have cognitive impairment at the time of enrollment.
Amyloid-positive with cognitive impairment (AD)	18F-Florbetaben	Amyloid-positive patients who already have cognitive impairment at the time of enrollment.
Amyloid-positive with cognitive impairment (AD)	Lumbar puncture (optional)	Amyloid-positive patients who already have cognitive impairment at the time of enrollment.
Amyloid-positive without impairment (preclinical AD)	11C-PBR28	Cognitively normal subjects who are amyloid-positive
Amyloid-positive without impairment (preclinical AD)	18F-Florbetaben	Cognitively normal subjects who are amyloid-positive
Amyloid-positive without impairment (preclinical AD)	Lumbar puncture (optional)	Cognitively normal subjects who are amyloid-positive
Amyloid-negative with cognitive impairment	11C-PBR28	Participants with cognitive impairment due to suspected non-AD pathophysiology
Amyloid-negative with cognitive impairment	18F-Florbetaben	Participants with cognitive impairment due to suspected non-AD pathophysiology
Amyloid-negative with cognitive impairment	Lumbar puncture (optional)	Participants with cognitive impairment due to suspected non-AD pathophysiology
Amyloid-negative without impairment (normal aging)	18F-Florbetaben	Cognitively normal subjects who are amyloid-negative on PET, and lack signs of neurodegeneration from other biomarkers
Amyloid-negative without impairment (normal aging)	Lumbar puncture (optional)	Cognitively normal subjects who are amyloid-negative on PET, and lack signs of neurodegeneration from other biomarkers

Primary Outcome Measures

Name	Time	Method
11C-PBR28 Binding	Up to 1 year from screening	In vivo quantification radioligand binding to TSPO expression on microglia in the brain, reported as standardized uptake value ratio (SUVR).

Secondary Outcome Measures

Name	Time	Method
18F-Florbetaben Binding	Up to 1 year from screening	In vivo quantification of radioligand binding to Amyloid-Beta protein in the brain, reported as standardized uptake value ratio (SUVR).
Cerebral Spinal Fluid (CSF) Biomarkers	Up to 1 year from screening	Protein analysis of cerebral spinal fluid.