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

NCT ID: NCT07234695

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-22
• Study Completion Date: 2028-07-31

Brief Summary

The purpose of this study is to evaluate whether levetiracetam can prevent epileptic seizures in patients with Alzheimer's disease associated with Down syndrome. It will also analyze whether it can delay the neurodegeneration associated with this disease.

Patients will be randomly assigned to one of two groups: one group will receive the active drug (levetiracetam), and the other will receive a placebo.

Both groups will receive the treatment for 96 weeks. Each patient will participate for a total of 2 years and 5 months.

Detailed Description

This study is a clinical trial that will examine the efficacy and safety of a medication called levetiracetam in people with Down syndrome and Alzheimer's disease.

Adults with Down syndrome have a high risk of developing Alzheimer's disease. Epilepsy frequently coexists in these patients, and is associated with a worse clinical outcome. The early dysfunction of inhibitory interneuronal circuits, found in epilepsy, contributes to cognitive decline in Alzheimer's disease patients. Modifying this abnormal activity with levetiracetam could have potential benefits in the treatment of Alzheimer's disease, beyond its benefits on epileptic seizures' control and interictal epileptic activity recorded on EEG. Levetiracetam is a widely used drug with a proven safety profile, with more than 20 years of commercialization. This trial will evaluate the preventive benefit on the development of epileptic seizures in Alzheimer's disease associated with Down syndrome and, secondarily, its effect on cognitive decline and Alzheimer's disease markers. If the described benefits of levetiracetam use are independent of its antiepileptic effect, it could be a drug with a potential disease-modifying effect in Alzheimer's disease.

Primary objective:

To evaluate the efficacy of levetiracetam as a preventive measure for bilateral tonic-clonic seizures at 96 weeks in adults with Alzheimer's disease associated with Down syndrome.

Secondary objectives:

1. To quantify the time to the first bilateral tonic-clonic seizure between groups (levetiracetam vs. placebo).

2. To evaluate the incidence of mortality between groups (levetiracetam vs. placebo).

3. To study changes in biomarkers related to Alzheimer's disease:

1. Functional changes (CAMDEX-DS)

2. Cognitive changes (CAMCOG, mCRT)

3. Plasma biomarkers (217-pTau, NfL)

4. Brain structure (cortical thickness, hippocampal volume, gray matter volume)

5. Epileptiform activity (EEG)

4. Safety: Incidence of adverse events and serious adverse events in the LEV vs. placebo groups.

A total of 120 participants will be included (60 per group).

The dose of levetiracetam to be used in this clinical trial is 1000 mg/day (two doses of 500mg each 12 hours) orally. During the first 4 weeks of the treatment period, LEV, treatment will be administered 500mg/d (250mg/12h) to facilitate the compliance. During the last 4 weeks of the treatment period, LEV will be administered 500mg/d (250mg/12h) to enable a gradual withdrawal.

Participants in placebo arm will receive placebo 1 capsule/12h during the 96 weeks of the treatment period.

The patients will have a total of 12 medical visits during their participation in the study. In those visits the following medical procedures will be carried out:

• Neuropsychological evaluation
• Blood analysis
• Magnetic resonance imaging (MRI)
• Electroencephalogram (EEG)

This study not only aims to improve the health and quality of life of people with Down syndrome but also to advance our general understanding of Alzheimer's disease, which could benefit more patients in the future.

Conditions

Down Syndrome; Down Syndrome (DS); Down Syndrome (Trisomy 21); Alzheimer Dementia; Alzheimer Dementia (AD); Alzheimer Disease; Alzheimer Disease (AD); Alzheimer Blood Biomarkers; Epilepsy; Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Levetiracetam 500 mg/12h

Tablets for twice daily administration for 96 weeks. During the first 4 weeks of the treatment period, LEV, treatment will be administered 500mg/d (250mg/12h) to facilitate the compliance. During the last 4 weeks of the treatment period, LEV will be administered 500mg/d (250mg/12h) to enable a gradual withdrawal.

Group Type: EXPERIMENTAL

Levetiracetam 500mg

Intervention Type: DRUG

Use of Levetiracetam to prevent Seizures in Symptomatic Alzheimer's Disease in adults with Down syndrome (the LESS-AD trial)

Placebo

Tablets for twice daily administration for 96 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Comparator

Interventions

Levetiracetam 500mg

Use of Levetiracetam to prevent Seizures in Symptomatic Alzheimer's Disease in adults with Down syndrome (the LESS-AD trial)

Intervention Type: DRUG

Placebo

Comparator

Intervention Type: DRUG

Eligibility Criteria

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.

Exclusion Criteria

• Subjects and/or their caregivers must be able to provide their consent before participating in any study-related procedures.

• 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

OTHER

Sponsor Role: collaborator

Hospital Universitario Marqués de Valdecilla

OTHER

Sponsor Role: collaborator

Fundación CITA Alzheimer

UNKNOWN

Sponsor Role: collaborator

University Hospital Virgen de las Nieves

OTHER

Sponsor Role: collaborator

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital Virgen de las Nieves

Granada, Andalusia, Spain

Site Status: NOT_YET_RECRUITING

Fundación CITA Alzheimer

Donostia / San Sebastian, Basque Country, Spain

Site Status: NOT_YET_RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Site Status: NOT_YET_RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, Spain

Site Status: RECRUITING

Hospital La Princesa

Madrid, , Spain

Site Status: NOT_YET_RECRUITING

Countries

Spain

Central Contacts

María Carmona Iragui, Doctor

Role: CONTACT

mcarmonai@santpau.cat

+34 93 556 59 56

Diego Real de Asúa Cruzat, Doctor

Role: CONTACT

diego.realdeasua@salud.madrid.org

Facility Contacts

Joaquín Escobar Sevilla, Doctor

Role: primary

escobarsevillaj@gmail.com

+34 958 02 00 00

Miren Altuna Azkargorta, Doctor

Role: primary

maltuna@cita-alzheimer.org

+34 943 02 17 92

Eloy Rodríguez Rodríguez, Doctor

Role: primary

eloymrod@gmail.com

+34 942 20 25 20

Maria Carmona Iragui, Doctor

Role: primary

mcarmonai@santpau.cat

+34 935565986

Diego Real de Asúa Cruzat, Doctor

Role: primary

diego.realdeasua@salud.madrid.org

+34 915 20 22 00

Other Identifiers

2024-516148-24-00

Identifier Type: CTIS

Identifier Source: secondary_id

IIBSP-LEV-2024-86

Identifier Type: -

Identifier Source: org_study_id