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

NCT07234695 | Recruiting Phase 3

• 2 other identifiers: IIBSP-LEV-2024-862024-516148-24-00
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Keywords

Down syndrome; epilepsy; Alzheimer; dementia; levetiracetam; prevention; placebo-controlled; epileptic seizures; Alzheimer's disease markers; phase III; randomized; double-blind; bilateral tonic-clonic seizure; 217-pTau; NfL

Outcome Measures

Primary Outcomes (1)

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

  Number (percentage) of subjects who do not develop a bilateral tonic-clonic epileptic seizure during the study treatment phase (96 weeks).

  From enrollment to the end of treatment at 96 weeks

Secondary Outcomes (24)

• Time to first bilateral tonic-clonic epileptic seizure

  days

• All-cause mortality

  percentage

• Time to death

  days

• Cognition

  CAMCOG-DS: change from baseline and week 96.

• Plasma biomarkers -217p-tau

  Change from baseline and week 96

Study Arms (2)

Levetiracetam 500 mg/12h

EXPERIMENTAL

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.

Drug: Levetiracetam 500mg

Placebo

PLACEBO COMPARATOR

Tablets for twice daily administration for 96 weeks.

Drug: Placebo

Interventions

Levetiracetam 500mg DRUG

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

Levetiracetam 500 mg/12h

Placebo DRUG

Comparator

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa: collaborator
• Hospital Universitario Marqués de Valdecilla: collaborator
• Fundación CITA Alzheimer: collaborator
• University Hospital Virgen de las Nieves: collaborator
• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead

Study Sites (5)

Hospital Virgen de las Nieves

Granada, Andalusia, 18014, Spain

NOT YET RECRUITING

Fundación CITA Alzheimer

Donostia / San Sebastian, Basque Country, 20009, Spain

NOT YET RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

NOT YET RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

RECRUITING

Hospital La Princesa

Madrid, 28006, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Down Syndrome; Alzheimer Disease; Epilepsy; Seizures; Dementia; Epilepsy, Tonic-Clonic

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Epilepsy, Generalized

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

María Carmona Iragui, Doctor

CONTACT

+34 93 556 59 56; mcarmonai@santpau.cat

Diego Real de Asúa Cruzat, Doctor

CONTACT

diego.realdeasua@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Clinical Research Associate, Project Manager, Data Manager
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase III, national, multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical trial to evaluate the safety and efficacy of levetiracetam as a preventive treatment for epileptic seizures in adults with Alzheimer's disease associated with Down syndrome.

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: November 18, 2025
• Study Start: December 22, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: January 12, 2026

Record last verified: 2025-12

Locations

ES (5)