What side effects are associated with this type of intervention?

Common treatments for Alzheimer's Disease include cholinesterase inhibitors (such as donepezil and galantamine) and memantine. Known side effects of cholinesterase inhibitors are generally gastrointestinal issues, weight loss, and dizziness, occurring in less than 20% of patients. Memantine, which is used for moderate to severe AD, has been shown to improve cognition with minimal side effects. Additionally, aducanumab, a newer treatment, has been associated with amyloid-related imaging abnormalities (ARIA), headache, falls, diarrhea, and confusion. Vitamin E, used for its antioxidant properties, is generally well-tolerated with a modest benefit in delaying functional progression.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Alzheimer's Disease, including cholinesterase inhibitors like donepezil and NMDA receptor antagonists like memantine. Recently, aducanumab, an amyloid beta-directed antibody, was approved for mild AD due to its ability to reduce amyloid plaques, although its clinical benefits remain uncertain. This approval was controversial due to mixed trial results and known risks. Research is ongoing into treatments that influence microglial activation and TSPO binding, which are important in the context of neuroinflammation and AD pathology.

What other types of research exist?

Promising novel alternatives to gene variant analysis for Alzheimer's Disease treatment in 2024 include disease-modifying therapies, drug repositioning, and the use of biomarkers to select and monitor treatment efficacy. These approaches aim to slow disease progression, repurpose existing drugs for new therapeutic uses, and improve the precision of clinical trials.

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Genetic Variants and Microglial Activation Imaging for Alzheimer's Disease

Phase 2

Recruiting

Led By William Kreisl, MD

Research Sponsored by William Charles Kreisl

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 50 and older at time of study entry

Meet criteria for amnestic mild cognitive impairment (single or mixed domain) or Alzheimer's disease, or have no cognitive impairment based on history, exam, and neuropsychological testing

Must not have

Past or present history of certain brain disorders other than MCI or AD

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.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial aims to understand how specific gene variants affect brain immune cells in Alzheimer's disease. It focuses on white, non-Hispanic individuals to validate previous findings. Researchers will use genetic analysis and brain imaging to study these effects.

Who is the study for?

This trial is for white, non-Hispanic or Latino individuals aged 50+, fluent in English, with mild Alzheimer's or no cognitive impairment. Participants must have a certain Clinical Dementia Rating and be able to consent. They need prior AD biomarker results or will undergo a PET scan. Exclusions include severe medical conditions, MRI contraindications, recent excessive research radiation exposure, chronic inflammatory/infectious diseases, and other brain disorders.

What is being tested?

The study tests how gene variants affect microglial activation in Alzheimer's using PET imaging agents: 11C-ER176 and 18F-florbetaben. It aims to validate known genetic influences on activated microglia proportion and discover new gene loci related to this process while assessing the functional impact of these variants.

What are the potential side effects?

While not explicitly listed here, potential side effects may include reactions at the injection site from radioligands used for PET scans (like redness or swelling), discomfort from blood draws, and typical risks associated with undergoing PET scans such as exposure to low levels of radiation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 50 years old or older.

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I have been diagnosed with mild cognitive impairment or Alzheimer's, or I have no cognitive issues.

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I have had a test showing amyloid presence consistent with Alzheimer's disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of brain disorders other than mild cognitive impairment or Alzheimer's.

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I have a chronic inflammatory or infectious disease like MS, IBD, RA, psoriasis, lupus, or HIV.

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I do not have uncontrolled epilepsy or multiple serious injuries.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Correlation between the chromosome 1 variant (rs2997325) and TSPO binding

Number of variants discovered in genome-wide association study (GWAS) that influence TSPO binding

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Cognitive ImpairmentExperimental Treatment2 Interventions

Subjects diagnosed with Alzheimer's disease (AD) or mild cognitive impairment (MCI) will have one PET scan with 11C-ER176, with arterial sampling. If the subject lacks known AD-biomarkers, they may undergo a 18F-florbetaben PET scan prior to the 11C-ER176 PET scan. Genome-wide genetic analysis will be performed. Participants will undergo an annual clinical evaluation and blood sample collection for 5 years to establish the trajectory of AD-related serum biomarkers and syndromic diagnoses.

Group II: No Cognitive ImpairmentActive Control2 Interventions

Healthy volunteers who are cognitively normal will have one PET scan with 11C-ER176, with arterial sampling. If the subject lacks known AD-biomarkers, they may undergo an 18F-florbetaben PET scan prior to the 11C-ER176 PET scan. Genome-wide genetic analysis will be performed. Participants will undergo an annual clinical evaluation and blood sample collection for 5 years to establish the trajectory of AD-related serum biomarkers and syndromic diagnoses.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

11C-ER176

2020

Completed Phase 2

~250

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Alzheimer's Disease (AD) include cholinesterase inhibitors like donepezil and galantamine, which enhance cholinergic function by preventing the breakdown of acetylcholine, and NMDA receptor antagonists like memantine, which regulate glutamate activity to prevent excitotoxicity. These treatments are important for AD patients as they aim to improve cognitive function and slow disease progression. Additionally, research into genetic variants that influence microglial activation and TSPO binding could lead to more targeted therapies, addressing the neuroinflammatory components of AD.

Combination Therapy in Alzheimer's Disease: Is It Time?Heterogeneity of Alzheimer's disease: consequence for drug trials?Proteomics in Traditional Chinese Medicine with an Emphasis on Alzheimer's Disease.