Identifying genetic factors affecting brain inflammation in Alzheimer's disease

Discovery and Validation of Genetic Variants Affecting Microglial Activation in Alzheimer's Disease With 11C-ER176

This study is trying to find out if certain genes are linked to brain inflammation in Alzheimer's disease to help develop better treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 250 (estimated)
• Ages: 50 Years and up
• Sex: All
• Sponsor: Columbia University (other)
• Drugs / interventions: radiation
• Locations: 1 site (New York, New York)
• Trial ID: NCT04840979 on ClinicalTrials.gov

What this trial studies

This study aims to validate a previously identified gene variant that influences microglial activation in Alzheimer's disease and to discover new genetic loci associated with this activation. Researchers will conduct genome-wide analyses to explore the relationship between genetic variants and microglial activation, using PET imaging and human tissue samples. The goal is to enhance understanding of how these genetic factors contribute to Alzheimer's disease and to pave the way for targeted immune-based therapies to prevent cognitive decline.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 50 and older with mild cognitive impairment or Alzheimer's disease, as well as cognitively healthy controls who self-identify as white, non-Hispanic or Latino.

Not a fit: Patients who do not meet the age or cognitive impairment criteria, or those who do not self-identify as white, non-Hispanic or Latino, may not benefit from this study.

Why it matters

Potential benefit: If successful, this research could lead to more effective treatments for Alzheimer's disease by targeting the underlying genetic factors of microglial activation.

How similar studies have performed: Other studies have shown promise in exploring genetic factors related to Alzheimer's disease, but this specific approach focusing on microglial activation is relatively novel.

Eligibility criteria

Inclusion criteria:

1. Age 50 and older at time of study entry.
2. 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.
3. 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.
4. 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.
5. Self-identify as white, non-Hispanic or Latino
6. Subjects must be ableto provide informed consent
7. Written and oral fluency in English
8. Able to participate in all scheduled evaluations and to complete all required tests and procedures.
9. 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. Such serious medical conditions include uncontrolled epilepsy and multiple serious injuries.
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. Participation in the last year in a clinical trial for a disease modifying drug for AD.
7. Inability to have a catheter in subject's vein for the injection of radioligand.
8. Inability to have blood drawn from subject's veins.
9. 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.
10. 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.

Where this trial is running

New York, New York

• Columbia University Irving Medical Center — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Philip De Jager, MD — Columbia University
• Study coordinator: Galen Ziaggi

Conditions: Alzheimer Disease, PET scan, Inflammation, Genetic testing, Cognitive Impairment