Recruiting
Phase 2

Levetiracetam

Sponsor:

Sunnybrook Health Sciences Centre

Code:

NCT07477431

Conditions

Hippocampal Hyperactivation

Prodromal Alzheimer Disease

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Not accepted

Interventions

Levetiracetam (LEV)

Placebo

Study Details

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. 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.

Conditions

Hippocampal Hyperactivation

Prodromal Alzheimer Disease

Study ID

NCT07477431

Start date

Oct 23, 2025

Status verified date

Nov, 2025

Completion date

Feb, 2028

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 55 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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:

1. 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
2. Participant is known to be amyloid or tau positive; and/or
3. 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.

Exclusion Criteria:

  • History of hypersensitivity to levetiracetam or any other ingredients in the study drug or placebo.
  • Significant neurological disease, including but not limited to:

1. Any type of cognitive impairment
2. History of transient ischemic attacks within 12 months of Screening
3. History of seizures within 12 months of Screening
4. Epilepsy
5. Parkinson's disease
6. Stroke (aside from subcortical lacunar infarcts)
7. Multiple sclerosis
8. Huntington's disease
9. Normal pressure hydrocephalus
10. Brain tumour (aside from benign tumours without mass effect, which are to be judged on a case-by-case basis)
11. Subdural hematoma
12. History of traumatic brain injury with persistent neurological deficits
13. Known structural brain abnormalities
  • Significant or unstable psychiatric disease, including but not limited to:

1. Schizophrenia
2. Bipolar disorder
3. Major depression which is not controlled in the opinion of the investigator
4. Score ≥10 on the Geriatric Depression Scale (GDS) at Screening
5. Presence of active suicidal ideation within the last 3 months as indicated by "yes" response to Question 4 or 5 on the Suicidal Ideation portion of the C-SSRS at Screening
6. Answered "yes" to any of the suicide-related behaviours within the last 3 months on the Suicidal Behavior portion of the C-SSRS
7. Hospitalized or treated for suicidal behavior within 5 years of Screening
8. Psychotic features, agitation, or behavioral problems within the last 3 months that could lead to difficulty complying with the protocol in the opinion of the investigator
  • Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening).
  • Significant or unstable systemic illness or medical condition that would in the investigator's judgment make the participant unsuitable for inclusion in the study, including but not limited to:

1. History of malignancy within 3 years of screening (except of basal or squamous cell carcinoma of the skin)
2. Moderate-severe chronic kidney disease, chronic obstructive pulmonary disease, or congestive heart failure
  • Any of the following findings on a current (completed during screening) or previous brain MRI/CT scan:

1. Severe white matter disease (Fazekas score66 = 3)
2. Stroke involving a major vascular territory
3. Subcortical lacunar infarcts >1.5cm in diameter
4. Encephalomalacia
5. Vascular malformations that are at high risk of hemorrhage
6. Infective lesions
7. Space-occupying lesions
8. Any other abnormality that would in the opinion of the investigator make the participant unsuitable for participation in the study
  • Any contraindications to MRI or MEG (e.g., pacemaker, ferromagnetic metal implants, claustrophobia).
  • Treatment with the following medications at time of screening or while in the study:

1. Anticonvulsant medications (unless taken for a different indication than seizures)
2. Methotrexate
  • eGFR <50ml/min/1.73m2 on screening bloodwork.
  • QTc interval >470 msec (males) or >480 msec (females) on screening ECG.
  • Clinically significant abnormal results on screening bloodwork that would in the opinion of the investigator make the participant unsuitable for inclusion in the study.

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Arm 1: Drug then Placebo

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

other: Arm 2: Placebo then Drug

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

Interventions

Levetiracetam (LEV)

Levetiracetam 125mg capsules BID for 28-35 days

Placebo

Placebo capsules BID for 28-35 days

Primary outcome measure

  • 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) ]

Central Contacts and Locations

Central contacts

Locations

Sunnybrook Health Sciences Centre

Recruiting

Toronto, Ontario, Canada, M4N 3M5

Contacts

Principal Investigator:

Sandra E Black, MD

Toronto Western Hospital

Recruiting

Toronto, Ontario, Canada, M5T 2S8

Contacts

Principal Investigator:

Mary Pat McAndrews, PhD

More Information

Sponsor

Sunnybrook Health Sciences Centre

Last update posted

Jul 29, 2026

Last verified

Nov, 2025

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Sunnybrook Health Sciences Centre on 2026-07-29.