Imaging Inflammation in Alzheimer's Disease

Patrick Lao

Status and phase: Completed; Phase 2

Conditions: Alzheimer's Disease

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02831283

1K23AG052633-01 (U.S. NIH Grant/Contract)

AAAO1151

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 60+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Age 60 and older.
2. 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.
3. Subjects unable to provide informed consent must have a surrogate decision maker
4. Written and oral fluency in English or Spanish.
5. Able to participate in all scheduled evaluations and to complete all required tests and procedures.
6. 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

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.
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 subjects above the allowable limits.
6. Low affinity binding on TSPO genetic screen.
7. Participation in the last year in a clinical trial for a disease modifying drug for AD.
8. Inability to have a catheter in subject's vein for the injection of radioligand.
9. Inability to have blood drawn from subject's veins.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 4 patient groups

Amyloid-positive with cognitive impairment (AD)

Experimental group

Description:

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

Treatment:

Procedure: Lumbar puncture (optional)

Drug: 11C-PBR28

Drug: 18F-Florbetaben

Amyloid-positive without impairment (preclinical AD)

Active Comparator group

Description:

Cognitively normal subjects who are amyloid-positive

Treatment:

Procedure: Lumbar puncture (optional)

Drug: 11C-PBR28

Drug: 18F-Florbetaben

Amyloid-negative with cognitive impairment

Active Comparator group

Description:

Participants with cognitive impairment due to suspected non-AD pathophysiology

Treatment:

Procedure: Lumbar puncture (optional)

Drug: 11C-PBR28

Drug: 18F-Florbetaben

Amyloid-negative without impairment (normal aging)

Active Comparator group

Description:

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

Treatment:

Procedure: Lumbar puncture (optional)

Drug: 11C-PBR28

Drug: 18F-Florbetaben