NCT07477431 is a Phase 2 clinical trial evaluating levetiracetam as a preventive treatment for individuals at risk for Alzheimer's disease. This trial represents a shift from treating established Alzheimer's disease to intervening in the preclinical phase, before significant cognitive decline occurs.
The trial is based on the hypothesis that neural hyperexcitability (subclinical epileptiform activity) begins years before clinical symptoms of Alzheimer's disease and may be a driving factor in disease progression. By treating at-risk individuals with levetiracetam before significant pathology accumulates, the trial aims to prevent or delay the onset of cognitive impairment.
| Field | Value |
|---|---|
| NCT Number | NCT07477431 |
| Official Title | Levetiracetam for Persons at Risk for Alzheimer's Disease |
| Phase | Phase 2 |
| Status | RECRUITING |
| Study Type | Interventional |
| Design | Randomized, double-blind, placebo-controlled |
| Enrollment | Estimated participants (to be determined) |
| Sponsor | To be confirmed |
| Start Date | 2024 (actual) |
| Primary Completion | To be confirmed |
| Study Completion | To be confirmed |
Research has established that subclinical epileptiform activity is common in Alzheimer's disease, with studies showing 22-50% of AD patients exhibiting epileptiform discharges on EEG without clinical seizures[1]. However, emerging evidence suggests this neural hyperexcitability begins even earlier—potentially during the preclinical stage when amyloid and tau pathology are accumulating but cognitive symptoms have not yet manifested.
Key findings supporting this approach include:
Preclinical neural dysfunction: Studies using EEG and magnetoencephalography (MEG) have detected abnormal neural oscillations in cognitively normal individuals with positive amyloid PET scans
Hyperactive networks: The default mode network and other cognitive networks show increased activity in preclinical AD, potentially reflecting compensatory mechanisms that may become pathological over time
Seizures as risk factor: Individuals with a history of seizures have an increased risk of developing AD, suggesting a shared mechanism between hyperexcitability and neurodegeneration
Levetiracetam is an antiepileptic drug with several mechanisms relevant to AD prevention[2]:
The advantages of levetiracetam for prevention include:
The trial enrolls individuals who are at elevated risk for developing Alzheimer's disease but do not yet have clinical symptoms. This population may include:
Amyloid-positive individuals: Those with elevated amyloid PET or CSF biomarkers indicating preclinical AD pathology
Genetically at-risk: Individuals with:
Age-based risk: Older adults (typically 60-85 years) with subjective cognitive complaints but normal cognitive testing
Biomarker-defined risk: Combinations of elevated tau, amyloid, and neurodegeneration biomarkers (AT(N) profile)
Preventing AD before clinical symptoms manifest offers several advantages:
Participants will be randomized to:
Cognitive assessments:
Neural assessments:
Biomarker assessments:
Safety monitoring:
This trial is closely related to several key topics in NeuroWiki:
Participants may experience:
Levetiracetam may cause:
Prevention trials require special considerations:
The NCT07477431 trial sits within a broader portfolio of levetiracetam trials for AD:
NCT03875638 - LeAD Trial: Phase 2, treating neural hyperexcitability in early AD (already enrolled/completed)
NCT07234695 - DS-AD Trial: Phase 3, preventing seizures in Alzheimer's disease in Down syndrome
Other prevention trials: Various anti-amyloid, anti-tau, and neuroprotective agents in preclinical and prodromal AD
This trial is currently RECRUITING. For the most current information on enrollment status, locations, and eligibility, please visit:
Vossel KA, et al. Seizures and epileptiform activity in the early stages of Alzheimer disease. JAMA Neurology. 2013. ↩︎
Cleveland NR, Kharazia V, Dedeken L. Levetiracetam: mechanisms of action. Handb Exp Pharmacol. 2019. ↩︎