NCT07477431

Levetiracetam for Persons at Risk for Alzheimer's Disease

A Proof-of-Concept, Multicentre, Phase IIb, Randomized Double-Blind Crossover Trial of Levetiracetam vs Placebo for Hippocampal Hyperactivity in Cognitively Normal Individuals at Risk for Alzheimer's Disease

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Sunnybrook Health Sciences Centre · Academic / Other
• Sex: All
• Age: 55 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to investigate whether very small doses of a drug called levetiracetam (LEV) may reduce abnormal brain signaling in individuals who are at an increased risk for developing Alzheimer's Disease (AD). The study is looking for individuals who have a parent or sibling with Alzheimer's disease (dementia), and who have memory complaints but are currently performing within normal limits on cognitive testing. During the screening period, a functional MRI (fMRI) scan of the brain will identify those participants who have the abnormal brain signaling that the study is looking to treat. All participants will receive 4 weeks of treatment with LEV and 4 weeks of treatment with placebo (a sugar pill), but it will not be known what order they will receive them in. Participants will undergo cognitive testing, genetic testing, and several brain imaging scans as part of the study. This is a pilot study, meaning that it is being carried out for the first time in a small number of participants. If the results show that treatment with LEV appears to be more beneficial than placebo in normalizing brain signaling, a larger study may follow. This study is only being carried out in Toronto, Canada.

Detailed description

People who have a family history of AD or dementia and subjective cognitive complaints (have memory complaints but are normal on memory testing) have been shown to have a somewhat increased risk of developing AD, compared to people without these risk factors. Changes in the brain associated with AD begin years before people start showing symptoms. One of these early changes involves an abnormal increase in brain signaling activity (hyperactivity) in the hippocampus (the memory area of the brain). This increase is similar to what is seen in epilepsy but on a smaller, unrecognizable scale. Studies have found that small doses of an antiepileptic medication called levetiracetam (LEV) reduce this hippocampal hyperactivity in people with amnestic Mild Cognitive Impairment, the phase of AD when people first begin showing memory symptoms. The study aims to determine if this hyperactivity can be detected and treated even earlier, before individuals start showing any symptoms. Participation begins with 3 screening visits that are a combination of questionnaires, cognitive tests, brain imaging, and collection of information on participant medical history, medications, and demographics. If participant eligibility is confirmed after the screening visits, they are randomly enrolled in one of the study arms. There are two treatment periods, one period where participants receive the study drug and one period where they receive a placebo (a substance that looks like the study drug but does not have any active or medicinal ingredients). Half of the study participants will receive LEV first, then placebo, while the other half will receive placebo first, then LEV. This crossover study design allows all eligible enrolled individuals to receive the study drug at some point. The study is double-blinded, meaning that the participants and study staff will not be aware of when participants are receiving the drug. From the day of consent, those participants who pass screening are expected to be in the study for approximately 6 months. Study procedures include cognitive testing, questionnaires, MRI Scans, EEG-MEG scans, physical and neurological exams, ECGs, blood sample collection for APOE genetic testing \& blood biomarker testing, optional blood sample collection for biobanking, and an amyloid PET scan. This study is only being carried out in Toronto, Canada. Participants will be recruited at several Toronto sites, but most of the study visits (for all participants) will take place at Toronto Western Hospital, part of the University Health Network.

Conditions

• Hippocampal Hyperactivation
• Prodromal Alzheimer Disease

Interventions

Type	Name	Description
DRUG	Levetiracetam (LEV)	Levetiracetam 125mg capsules BID for 28-35 days
OTHER	Placebo	Placebo capsules BID for 28-35 days

Timeline

• Start date: 2025-10-23
• Primary completion: 2027-01-01
• Completion: 2027-02-01
• First posted: 2026-03-17
• Last updated: 2026-03-17

Locations

2 sites across 1 country: Canada