Levetiracetam for Persons at Risk for Alzheimer's Disease

NCT07477431 | Recruiting Phase 2 DMC

• 1 other identifier: 4811
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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. 1.People who feel like their memory is getting worse and who have a parent or sibling with Alzheimer's disease (dementia)
2. 2.People with two copies of the APOE E4 gene
3. 3.People who have tested positive for a biomarker of AD (e.g., blood p-tau test, brain amyloid PET scan)

Conditions

Hippocampal Hyperactivation; Prodromal Alzheimer Disease

Keywords

EEG-MEG; fMRI; Pattern Separation Task; PST; Levetiracetam; Crossover Design; AD; Prodromal AD; Hippocampal hyperactivation; Subjective cognitive complaints; Alzheimer Disease

Outcome Measures

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

  Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)

Secondary Outcomes (4)

• Behavioural performance on the PST as a function of LEV vs placebo

  Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)

• Frequency of epileptiform discharges on EEG as a function of LEV vs placebo

  Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)

• Power spectrum analysis for hippocampus in resting-state MEG as a function of LEV vs placebo

  Before and after each treatment phase (Screening/Baseline, Week 4, Week 8, Week 12)

• Changes in hippocampal signal in MEG during repetition suppression task as a function of LEV vs placebo

  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

  Adverse events will be captured from randomization (Day 0) to study completion (Day 98-119).

Study Arms (2)

Arm 1: Drug then Placebo

OTHER

Participants randomized to Arm 1 will receive LEV in Treatment Phase I and placebo in Treatment Phase II.

Drug: Levetiracetam (LEV); Other: Placebo

Arm 2: Placebo then Drug

OTHER

Participants randomized to Arm 2 will receive placebo in Treatment Phase I and LEV in Treatment Phase II.

Drug: Levetiracetam (LEV); Other: Placebo

Interventions

Levetiracetam (LEV) DRUG

Levetiracetam 125mg capsules BID for 28-35 days

Arm 1: Drug then Placebo; Arm 2: Placebo then Drug

Placebo OTHER

Placebo capsules BID for 28-35 days

Arm 1: Drug then Placebo; Arm 2: Placebo then Drug

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Sufficiently fluent in English to undergo cognitive testing, per investigator judgment
• Increased risk of Alzheimer's disease, as indicated by one or more of the following:
• Participant has subjective cognitive complaints AND a family history of Alzheimer's disease (or of dementia suggestive of possible or probable Alzheimer's disease) in a first-degree relative; and/or
• Participant is known to be amyloid or tau positive; and/or
• Participant is known to be an APOE e4/e4 homozygote
• Hippocampal hyperactivation, defined as activation \>1.5 MAD above the median, during the pattern separation task (PST) on BOLD fMRI.

You may not qualify if:

• History of hypersensitivity to levetiracetam or any other ingredients in the study drug or placebo.
• Significant neurological disease, including but not limited to:
• Any type of cognitive impairment
• History of transient ischemic attacks within 12 months of Screening
• History of seizures within 12 months of Screening
• Epilepsy
• Parkinson's disease
• Stroke (aside from subcortical lacunar infarcts)
• Multiple sclerosis
• Huntington's disease
• Normal pressure hydrocephalus
• Brain tumour (aside from benign tumours without mass effect, which are to be judged on a case-by-case basis)
• Subdural hematoma
• History of traumatic brain injury with persistent neurological deficits
• Known structural brain abnormalities

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• University Health Network, Toronto: collaborator
• Weston Brain Institute: collaborator

Study Sites (2)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sandra E. Black, MD, FRCP(C)

  Sunnybrook Health Sciences Centre, University of Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

ALEVIATE-2 Project Manager

CONTACT

416-480-6100 ext. 63004; aleviate-2@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: March 17, 2026
• Study Start: October 23, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: July 29, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Start date: two years after publication of the study results (main publication). No planned end date.
• Access Criteria: The data will be stored in controlled-access databases, for which access is limited to researchers who submit a study plan to the study publications and data sharing committee, and who sign an agreement to use the coded study data only for that research. The study will be listed in the GAAIN (Global Alzheimer's Association Interactive Network) registry once data becomes available.

Locations

CA (2)