Levetiracetam for Persons at Risk for Alzheimer's Disease (ALEVIATE-2)

Full study title: 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 (ALEVIATE-2)

What is the study about?

The goal of this study is to learn whether very small doses of a drug called levetiracetam (LEV) may lower unusual brain signals in individuals who are at an increased risk for developing Alzheimer's Disease. Only participants who complete a functional MRI (fMRI) scan of the brain, and show unusual brain signaling, can participate in the study. Participants will receive 4 weeks of treatment with LEV and 4 weeks of treatment with placebo (a non-medical sugar pill). Participants will also complete cognitive testing, genetic testing, bloodwork, electrocardiograms (ECGs), questionnaires and several brain imaging scans. 

Eligibility- Who can participate?

Participants must:

• Be between 55-85 years of age
• Have a parent or sibling with Alzheimer’s disease or with dementia that may be due to Alzheimer’s disease (AD diagnosis not required)
• Feel their memory is getting worse
• Get normal scores on tests of thinking and memory
• Be able to undergo brain MRI scans
• Have a study partner (friend or family member) willing to answer questionnaires about the participant
• Show increased brain signaling in the memory area of the brain during the screening fMRI scan (note: many people will not meet eligibility criteria based on the fMRI scan results)

Time requirement

The total study duration will be up to 7 months.

Screening

• 3 screening visits over 1-3 months to check if participants are eligible for the study
• Each visit will take 1-4 hours
• First screening visit can occur at any of the participating study sites, but all of the subsequent visits will occur at Toronto Western Hospital
• Screening visits involve cognitive tests, questionnaires, collection of information on medical history, current medications, social history, and family history, an MRI brain scan, bloodwork, physical exam, and ECG

Follow-up visits

• 4 visits (Baseline, Week 4, Week 8 and Week 12) 4 to 5 weeks apart - medication dispensing and return, MRI, EEG-MEG, ECG, bloodwork, blood for APOE genotyping and blood biomarkers of AD, cognitive tests, questionnaires, physical exams, review of medications, and checking for adverse events
  • Visit 1 (baseline) – 4 hours
  • Visits 2-4 – 7-8 hours long
• 1 amyloid PET visit  (2 hours) and 1 follow-up phone call (15 minutes)