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.
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/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.
Parallel
Levetiracetam 500mg
DrugUse of Levetiracetam to prevent Seizures in Symptomatic Alzheimer's Disease in adults with Down syndrome (the LESS-AD trial)
Placebo
DrugComparator
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).
Time to first bilateral tonic-clonic epileptic seizure
Baseline (randomization) to first adjudicated epileptic seizure or censoring, up to 96 weeks.
All-cause mortality
* All-cause mortality (number and percentage) - Time Frame: Baseline (randomization) to study completion, up to 96 weeks. * Alzheimer-related mortality (number and percentage) - Time Frame: Baseline (randomization) to study completion, up to 96 weeks.
Time to death
Baseline (randomization) to death or censoring, up to 96 weeks.
Cognition
CAMCOG-DS (total score): change from baseline and week 96. Change from baseline visit in the CAMCOG-DS total score. Missing visits will be handled per the statistical analysis plan.
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Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Lead sponsor
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
