Discovery and Validation of Genetic Variants Affecting Microglial Activation in Alzheimer's Disease
Discovery and Validation of Genetic Variants Affecting Microglial Activation in Alzheimer's Disease With 11C-ER176
Columbia University
250 participants
May 11, 2021
INTERVENTIONAL
Conditions
Summary
The primary objectives are to validate that a previously identified gene variant influences the proportion of activated microglia (PAM) and the amount of TSPO binding on PET imaging, to identify novel loci that influence PAM and TSPO PET, and to understand the functional consequences of gene variants that drive microglial activation in Alzheimer's disease.
Eligibility
Inclusion Criteria9
- Age 50 and older at time of study entry.
- Meet criteria for either a) amnestic mild cognitive impairment (single or mixed domain) or Alzheimer's disease, or b) have no cognitive impairment, based on history, exam, and neuropsychological testing.
- 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 must have AD biomarker previously obtained for research or clinical purposes or undergo a 18F-florbetaben PET scan during the screening process. Patients must have positive amyloid PET scan or CSF results consistent with AD. Controls must have a negative amyloid PET scan or CSF results not consistent with AD.
- Self-identify as white, non-Hispanic or Latino
- Subjects must be ableto provide informed consent
- Written and oral fluency in English
- 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 Criteria10
- 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. 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.
- 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.
- Taking anticoagulant (e.g., warfarin) or immunosuppressive/immunomodulatory medication. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not exclusionary. Use of steroids in the 30 days preceding the PET scan.
- Having a diagnosis of a chronic inflammatory disease (for example, multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus) or a chronic infectious disease such as H.I.V.
Interventions
11C-ER176 is a novel TSPO radioligand that was developed because of its relative insensitivity to the rs6971 polymorphism. Increased TSPO signal on PET is associated with activation of microglia in the brain. The radioligand will be administered in tracer doses at activity of up to 20 mCi (740 MBq), IV, total of one injection. A single dose of radioligand will be injected over 1 minute.
Florbetaben has been approved by the FDA to help diagnose Alzheimer's disease. Florbetaben measures amyloid in the brain.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04840979