Levetiracetam for Persons at Risk for Alzheimer's Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age55-85
SponsorSunnybrook Health Sciences Centre
About this trial
The goal of this clinical trial is to investigate whether very small doses of a drug called levetiracetam (LEV) may reduce elevated brain signaling in individuals who are at an increased risk for developing Alzheimer's Disease (AD). The study is looking for people who are currently performing within normal limits on memory testing but who have one or more of the following risk factors for developing AD:
1. People who feel like their memory is getting worse and who have a parent or sibling with Alzheimer's disease (dementia) 2. People with two copies of the APOE E4 gene 3. People who have tested positive for a biomarker of AD (e.g., blood p-tau test, brain amyloid PET scan)
During the screening period, a functional MRI (fMRI) scan of the brain will identify those participants who have the increased 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Willing to undergo all study procedures and has signed the informed consent form
Within normal limits on the Montreal Cognitive Assessment (MoCA) at Screening
Age 55-85
Female participants must be post-menopausal (amenorrheic for at least 12 consecutive months without other known or suspected cause) or surgically sterile (bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy)
Disqualifiers
History of hypersensitivity to levetiracetam or any other ingredients in the study drug or placebo.
Any type of cognitive impairment
History of transient ischemic attacks within 12 months of Screening
History of seizures within 12 months of Screening
Trial design
Design model
Crossover
Treatments tested in this trial
Levetiracetam (LEV)
DrugLevetiracetam 125mg capsules BID for 28-35 days
Placebo
Other interventionPlacebo capsules BID for 28-35 days
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: Arm 1: Drug then PlaceboOther 2 interventions
Group B: Arm 2: Placebo then DrugOther 2 interventions
Trial outcomes
Primary outcomes
1
Level of fMRI activity in the hippocampus and entorhinal cortex during a pattern separation task (PST), as a function of LEV vs placebo
Time frame
Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)Secondary outcomes
1
Behavioural performance on the PST as a function of LEV vs placebo
Evaluation of participant's ability to correctly discriminate between presented stimuli as old, new, or similar. The lure discrimination index (LDI) is based on the proportion of the presented lures correctly called similar and the proportion of lures incorrectly called old.
Time frame
Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)2
Frequency of epileptiform discharges on EEG as a function of LEV vs placebo
Resting-state EEG
Time frame
Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)3
Power spectrum analysis for hippocampus in resting-state MEG as a function of LEV vs placebo
Power in specific frequency bands (theta, alpha, beta) will be analyzed.
Time frame
Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)4
Changes in hippocampal signal in MEG during repetition suppression task as a function of LEV vs placebo
Beta band power (desynchronization) will be measured with novel versus repeated presentation of images in the repetition suppression task.
Time frame
Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)Other outcomes
1
Assessment of the relative safety and tolerability of LEV compared to placebo
The number of adverse events and number of serious adverse events reported will be used to assess the safety of LEV compared to placebo.
Time frame
Adverse events will be captured from randomization (Day 0) to study completion (Day 98-119).Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Sunnybrook Health Sciences Centre
Lead sponsor
University Health Network, Toronto
Collaborator
Weston Brain Institute
Collaborator
Source ClinicalTrials.gov