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LESS-AD

RecruitingPhase 3

LEvetiracetam to Prevent Seizures in Symptomatic Alzheimer's Disease in Adults With Down Syndrome

A Phase III, Randomized, Double-blinded Study of the Efficacy and Safety of LEvetiracetam to Prevent Seizures in Symptomatic Alzheimer's Disease in Adults With Down Syndrome (the LESS-AD Trial).

Asset

Levetiracetam

Listed sites

5

Recruiting sites

1

Enrollment

120

estimated

Study population

Alzheimer’s disease

Key I/E criterion

•Age ≥40

Primary endpoint

•Efficacy of Levetiracetam as a preventive treatment for epileptic seizures

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

Ctis2024-516148-24-00
Org study IDIIBSP-LEV-2024-86
NCT IDNCT07234695

Timeline

Milestones

Study first posted2025-11-18actual
Study start2025-12-22estimated
Last update posted2026-01-12actual
Primary completion2027-12estimated (month precision)
Study completion2028-07estimated (month precision)

Assets

Drug assets

Levetiracetam

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age40 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

•Diagnosed with Down Syndrome (DS), either with a karyotype or a compatible typical phenotype.
•Age over 40 years at time of screening.
•Symptomatic Alzheimer's Disease (AD) dementia, based on change in functionality and neuropsychological tests' results. Different cut-off points will be established to diagnose dementia depending on the level of intellectual disability of the individual, according to previous experience (Benejam et al; 2020): in adults with mild intellectual disability, a CAMCOG-DS score of 80 and an mCRT score of 29 will be chosen, whereas values of 56 and 28, respectively, will be used in subjects with moderate intellectual disability. Doubtful cases (e.g., with compromised functionality, but without alteration in the neuropsychological assessment) or those unable to complete the evaluation will be categorized by consensus among expert clinicians, using all available clinical information.
•Willing and able caregiver who has daily contact with the study subject.
•Subjects and caregivers must be able to comply with the prescribed regimen of study treatment throughout the course of the study and meet a minimum required time commitment of biannual in-person visits.
•Any concurrent treatment for AD approved by the European Medicines Agency (EMA) must be stable for at least 30 days prior to screening and at least 60 days prior to study day 1. Other medications (except for those listed under exclusion criteria) are allowed as long as the dose is stable for 30 days prior to screening.
•Subjects and/or their caregivers must be able to provide their consent before participating in any study-related procedures

Exclusion criteria

•Cognitive changes attributable to causes other than AD (for example, but not limited to, uncorrected visual or hearing deficit, severe, untreated sleep apnea or uncontrolled thyroid disorders).
•Previous history of adult-onset epileptic seizures (over 18 years old).
•Treatment with any kind of antiepileptic drugs, benzodiazepines, narcotics.
•Significant comorbidities or analytical abnormalities, such as:
•Any unstable and/or clinically significant medical condition likely to hamper the evaluation of safety and/or efficacy of the study (eg, moderate and/or severe untreated obstructive sleep apnea, clinically significant reduction in serum B12 or folate levels, clinically significant abnormalities of thyroid function, stroke, or other cerebrovascular conditions), as per investigator's judgement.
•Severe renal dysfunction (creatinine clearance < 30 mL/min), which would affect serum levetiracetam levels, or any other medical condition which is determined by the investigators to potentially create an undue risk for an adverse effect.
•Concomitant or past history psychiatric or neurologic disorder other than those considered to be related to AD (eg, head injury with loss of consciousness, symptomatic stroke, Parkinson's disease, severe carotid occlusive disease, transient ischemic attacks [TIAs]).
•Significant risk of suicide, defined using the C-SSRS as the subject answering "yes" to suicidal ideation questions 4 or 5 or answering "yes" to suicidal behavior within the past 12 months.
•Deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, judged to be clinically significant by the investigator.
•Participation in another clinical trial within 3 months of screening.
•Hypersensitivity to the active ingredient, other pyrrolidone derivatives, or any of the excipients
•Pregnant and breastfeeding patients

Endpoints (25)

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

Safety / tolerability / PK
6
Neuroimaging
4
Other clinical outcomes
4
Other (unclassified)
4
Fluid / digital biomarkers
3
Global cognition
1
Behavior / neuropsychiatric
1
Tau biomarkers
1
Neurodegeneration biomarkers
1

Global cognition

1 endpoint
Secondary/protocol endpoint

Cognition

Time frame:CAMCOG-DS: change from baseline and week 96.

change from baseline, improvement

Behavior / neuropsychiatric

1 endpoint
Secondary/protocol endpoint

Suicidality (C-SSRS)

Time frame:Week 96

threshold achievement, improvement

Tau biomarkers

1 endpoint
Secondary/protocol endpoint

Plasma biomarkers -217p-tau

Time frame:Change from baseline and week 96

change from baseline, improvement

Neurodegeneration biomarkers

1 endpoint
Secondary/protocol endpoint

Plasma biomarkers- NfL

Time frame:At week 96

Neurofilament light (NfL)

change from baseline, improvement

Neuroimaging

4 endpoints
Secondary/protocol endpoint

Neuroimaging- HV

Time frame:Change at week 96

change from baseline, improvement

Secondary/protocol endpoint

Neuroimaging CTh

Time frame:Week 96

change from baseline, improvement

Secondary/protocol endpoint

Safety of Levetiracetam

Time frame:From enrollment to the end of treatment at 96 weeks

event count, event

Secondary/protocol endpoint

Brain MRI safety

Time frame:At week 96

threshold achievement, improvement

Fluid / digital biomarkers

3 endpoints
Secondary/protocol endpoint

Electroencephalography (EEG)

Time frame:At week 96.

threshold achievement, improvement

Secondary/protocol endpoint

EEG- band power

Time frame:At week 96

change from baseline, improvement

Secondary/protocol endpoint

EEG sync

Time frame:At week 96

change from baseline, improvement

Safety / tolerability / PK

6 endpoints
Secondary/protocol endpoint

Incidence of adverse events (AEs)

Time frame:At week 96

threshold achievement, event

Secondary/protocol endpoint

AEs- TEAE rate

Time frame:Up to week 36

descriptive

Secondary/protocol endpoint

Maximum AE severity

Time frame:At week 96

threshold achievement, event

Secondary/protocol endpoint

Vital signs- BP

Time frame:At week 96

change from baseline, event

Secondary/protocol endpoint

Vital signs- HR

Time frame:At week 96

change from baseline, event

Secondary/protocol endpoint

Laboratory safety

Time frame:At week 96

threshold achievement, event

Other clinical outcomes

4 endpoints
Primary/protocol endpoint

Efficacy of Levetiracetam as a preventive treatment for epileptic seizures in adults with Alzheimer's disease associated with Down syndrome.

Time frame:From enrollment to the end of treatment at 96 weeks

event count, event

Secondary/protocol endpoint

Time to first bilateral tonic-clonic epileptic seizure

Time frame:days

time to event, event

Secondary/protocol endpoint

All-cause mortality

Time frame:percentage

descriptive

Secondary/protocol endpoint

Time to death

Time frame:days

time to event, event

Other (unclassified)

4 endpoints
Secondary/protocol endpoint/low confidence

Neuroimaging GMV

Time frame:At week 96

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Neuroimaging- LVV

Time frame:Week 96

change from baseline, improvement

Secondary/protocol endpoint/low confidence

AEs- Dose interruptions

Time frame:At week 96.

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

Physical examination

Time frame:Week 96

threshold achievement, improvement

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.