Levetiracetam to prevent seizures in adults with Down syndrome and Alzheimer's disease
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).
This trial will test whether the anti-seizure medicine levetiracetam can prevent tonic-clonic seizures and slow cognitive decline in adults over 40 who have Down syndrome and symptomatic Alzheimer's disease.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 120 (estimated) |
| Ages | 40 Years and up |
| Sex | All |
| Sponsor | Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau Academic / other |
| Locations | 5 sites (Granada, Andalusia and 4 other locations) |
| Trial ID | NCT07234695 on ClinicalTrials.gov |
What this trial studies
This is a randomized, placebo-controlled Phase 3 trial giving levetiracetam or matching placebo for 96 weeks to adults with Down syndrome who have symptomatic Alzheimer's dementia. Participants are randomly assigned to active drug or placebo and followed for clinical seizure outcomes, cognitive measures, and Alzheimer’s disease biomarkers. The primary outcome is prevention of bilateral tonic-clonic seizures at 96 weeks, with secondary outcomes including time to first seizure, changes in cognition, and safety. The trial uses standard dosing of levetiracetam and regular clinic visits at participating Spanish centers.
Who should consider this trial
Good fit: Adults with Down syndrome aged over 40 who have symptomatic Alzheimer's dementia and a willing daily caregiver, and who can attend study visits at the trial sites, are the intended participants.
Not a fit: People without Down syndrome or without symptomatic Alzheimer's dementia, those under 40, or individuals with medical conditions that preclude study participation are unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, levetiracetam could reduce seizure risk and may slow neurodegeneration, improving safety and cognitive outcomes for adults with Down syndrome and Alzheimer's disease.
How similar studies have performed: Small clinical and preclinical studies indicate levetiracetam can reduce network hyperexcitability and sometimes improve cognition in Alzheimer's models and early human work, but preventive use in Down syndrome–associated Alzheimer's remains largely untested.
Eligibility criteria
Show full inclusion / exclusion 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. * 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
Where this trial is running
Granada, Andalusia and 4 other locations
- Hospital Virgen de las Nieves — Granada, Andalusia, Spain (Not_yet_recruiting)
- Fundación CITA Alzheimer — Donostia / San Sebastian, Basque Country, Spain (Not_yet_recruiting)
- Hospital Universitario Marqués de Valdecilla — Santander, Cantabria, Spain (Not_yet_recruiting)
- Hospital de la Santa Creu i Sant Pau — Barcelona, Catalonia, Spain (Recruiting)
- Hospital La Princesa — Madrid, Spain (Not_yet_recruiting)
Study contacts
- Study coordinator: María Carmona Iragui, Doctor
- Email: mcarmonai@santpau.cat
- Phone: +34 93 556 59 56
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.