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

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.

Interventions

• Levetiracetam 500mg · DRUG

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

• Placebo · DRUG

  Comparator

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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

Sites (5)

• 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