ALEVIATE-2

RecruitingPhase 2

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

Lead sponsor

Sunnybrook Health Sciences Centre

Asset

Levetiracetam

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Alzheimer’s disease

Key I/E criteria

•Family history of Alzheimer’s disease required•Study partner/caregiver required•MRI contraindications excluded

Primary endpoint

•Level of fMRI activity in the hippocampus

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID4811

NCT IDNCT07477431

Timeline

Milestones

Study start2025-10-23actual

Study first posted2026-03-17actual

Last update posted2026-03-17actual

Primary completion2027-01estimated (month precision)

Study completion2027-02estimated (month precision)

Assets

Drug assets

Levetiracetam

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Willing to undergo all study procedures and has signed the informed consent form.

•Has a friend or family member who has weekly contact with the participant and is willing to sign the study partner informed consent and complete study questionnaires.

•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.

•Presence of subjective cognitive complaints, indicated by score >7 on MyCog portion of the Subjective Cognitive Decline Questionnaire (SCD-Q) at Screening.

•Family history of Alzheimer's disease or of dementia suggestive of possible or probable Alzheimer's disease in a first-degree relative.

•Head circumference <60cm.

•Within normal limits on all domains of the Toronto Cognitive Assessment (TorCA) at Screening or in the previous 6 months, with the exceptions noted below:

1. A borderline score on the executive domain may be acceptable if in the opinion of the investigator it is solely attributable to the participant having ADHD.

2. A borderline score on the language domain may be acceptable if in the opinion of the investigator it is solely attributable to English not being the participant's primary language.

•Known to be within normal limits on the Montreal Cognitive Assessment (MoCA), Cogniciti Brain Health Assessment (BHA), or Toronto Cognitive Assessment (TorCA) in the previous 6 months, or within normal limits on the MoCA at Screening.

•Hippocampal hyperactivation, defined as activation >1.5 SD above the mean, 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

9. Score ≥9 on the Mild Behavioural Impairment Checklist (MBI-C) at Screening

•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

2. Methotrexate

3. Anticholinergic agents and medications with anticholinergic properties

•Creatinine clearance <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.

Endpoints (6)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Neuroimaging

Fluid / digital biomarkers

Safety / tolerability / PK

Neuroimaging

1 endpoint

Primary/protocol endpoint

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)

ratio, descriptive

Fluid / digital biomarkers

1 endpoint

Secondary/protocol endpoint

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

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

event count, event

Safety / tolerability / PK

1 endpoint

Other/protocol endpoint

Assessment of the relative safety and tolerability of LEV compared to placebo

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

event count, event

Other (unclassified)

3 endpoints

Secondary/protocol endpoint/low confidence

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

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

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

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

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

event count, event

Secondary/protocol endpoint/low confidence

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

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

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.