Down SyndromePhase 3LESS-ADNCT07234695
LEvetiracetam to Prevent Seizures in Symptomatic Alzheimer's Disease in Adults With Down Syndrome
A Phase 3 study testing Levetiracetam 500mg in people with Down Syndrome and Down Syndrome (DS), run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 5 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Down Syndrome, Down Syndrome (DS), Down Syndrome (Trisomy 21)
- What is being tested?
- Levetiracetam 500mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 5 sitesSpain
- Study dates
- 22 Dec 2025to Jul 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Diego Real de Asúa Cruzat, Doctor contact
5 sites in 1 country
Spain5 sites, 5 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, Catalonia, 08041
Maria Carmona Iragui, Doctor, +34 935565986, mcarmonai@santpau.cat
- Not yet recruiting
Fundación CITA Alzheimer
Donostia / San Sebastian, Basque Country, 20009
Miren Altuna Azkargorta, Doctor, +34 943 02 17 92, maltuna@cita-alzheimer.org
- Not yet recruiting
Hospital Virgen de las Nieves
Granada, Andalusia, 18014
Joaquín Escobar Sevilla, Doctor, +34 958 02 00 00, escobarsevillaj@gmail.com
- Not yet recruiting
Hospital La Princesa
Madrid, 28006
Diego Real de Asúa Cruzat, Doctor, +34 915 20 22 00, diego.realdeasua@salud.madrid.org
- Not yet recruiting
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, 39008
Eloy Rodríguez Rodríguez, Doctor, +34 942 20 25 20, eloymrod@gmail.com
About this study
Official title: 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).
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.
Read the 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:
- To quantify the time to the first bilateral tonic-clonic seizure between groups (levetiracetam vs. placebo).
- To evaluate the incidence of mortality between groups (levetiracetam vs. placebo).
- To study changes in biomarkers related to Alzheimer's disease:
- Functional changes (CAMDEX-DS)
- Cognitive changes (CAMCOG, mCRT)
- Plasma biomarkers (217-pTau, NfL)
- Brain structure (cortical thickness, hippocampal volume, gray matter volume)
- Epileptiform activity (EEG)
- 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
- Being tested
- Levetiracetam 500mg, Placebo
- 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
- Medical subject headings
- Down Syndrome, Alzheimer Disease, Epilepsy, Seizures, Dementia, Epilepsy, Tonic-Clonic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levetiracetam 500mgDrug
Use of Levetiracetam to prevent Seizures in Symptomatic Alzheimer's Disease in adults with Down syndrome (the LESS-AD trial)
PlaceboDrug
Comparator
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Levetiracetam 500mg |
| Placebo | Placebo comparator | Tablets for twice daily administration for 96 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From enrollment to the end of treatment at 96 weeks
Secondary outcomes (24)
Time to first bilateral tonic-clonic epileptic seizure
Baseline (randomization) to first adjudicated epileptic seizure or censoring, up to 96 weeks.
Measured: days
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.
Measured: percentage
Time to death
Baseline (randomization) to death or censoring, up to 96 weeks.
Measured: days
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.
Measured: CAMCOG-DS: change from baseline and week 96.
Plasma biomarkers -217p-tau
Plasma pTau-217-change (pg/mL) from baseline and week 96. Change from baseline in plasma pTau-217 concentration, quantified using the same laboratory and assay throughout the study.
Measured: Change from baseline and week 96
Plasma biomarkers- NfL
Plasma Neurofilament light (NfL) (pg/mL) - Change from Baseline. Change from Baseline in plasma NfL concentration.
Measured: At week 96
Neuroimaging GMV
Subcortical gray matter volume - change from Baseline (by region). Change from Baseline in volume (mm³) for 12 subcortical gray matter regions (left/right: amygdala, caudate, nucleus accumbens, pallidum, putamen, thalamus). Each region will be reported separately.
Measured: At week 96
Neuroimaging- HV
Hippocampal volume (mm3)- Change from Baseline (left and right). Change from Baseline in hippocampal volume for the left and right hemispheres. Each hemisphere will be reported separately.
Measured: Change at week 96
Neuroimaging- LVV
Lateral ventricle volume (mm3) - Change from Baseline (left and right). Change from Baseline in lateral ventricle volume for the left and right hemispheres. Each hemisphere will be reported separately.
Measured: Week 96
Neuroimaging CTh
Cortical thickness (mm) - Change from Baseline (by region). Change from Baseline in cortical thickness (mm) for 34 left-hemispheric and 34 right-hemispheric cortical regions. Each region will be reported separately.
Measured: Week 96
Electroencephalography (EEG)
Presence of epileptiform/irritative graphoelements. Proportion of participants showing irritative graphoelements (spike-wave, polyspike-wave, sharp waves, focal or generalized slowing) per standardized EEG reading.
Measured: At week 96.
EEG- band power
EEG band power (µV²/Hz) - Change from Baseline. Change from Baseline in mean band power (δ, θ, α, β, γ) computed with a prespecified processing pipeline.
Measured: At week 96
EEG sync
EEG synchronization/coherence (unitless index (0-1)) - Change from Baseline (by band). Change from Baseline in synchronization/coherence indices by frequency band (dimensionless 0-1) across predefined electrode pairs.
Measured: At week 96
Safety of Levetiracetam
The primary endpoints are number, type, frequency, and intensity of AEs evaluated until the end of treatment and assessment of tolerability during the medical visit, physical and neurological examination, vital signs, brain MRI assessment, suicidality (as measured with the C-SSRS), routine hematology and biochemistry evaluation in blood.
Measured: From enrollment to the end of treatment at 96 weeks
Incidence of adverse events (AEs)
Proportion (%) of participants:
- with ≥1 treatment-emergent adverse events (TEAEs)
- with TEAEs considered related to the treatment by the investigator
- with ≥1 serious adverse events (SAEs) after first dose of treatment
- who discontinue the study due to AEs
Measured: At week 96
AEs- TEAE rate
TEAE rate- Rate of TEAEs per participant-year of exposure.
Measured: Up to week 36
Maximum AE severity
Proportion of participants with at least one TEAE of maximum severity mild, moderate, or severe (% reported by category).
Measured: At week 96
AEs- Dose interruptions
Dose interruptions due to AEs. Proportion of participants with ≥1 levetiracetam dose interruption or reduction attributable to AEs.
Measured: At week 96.
Vital signs- BP
Systolic and diastolic blood pressure (mmHg)- Change from Baseline in systolic and diastolic blood pressure.
Measured: At week 96
Vital signs- HR
Heart rate. Change from Baseline in resting heart rate (bpm).
Measured: At week 96
Physical examination
Clinically significant abnormalities on physical/neurological exam. Proportion of participants with new or worsening clinically significant findings on physical or neurological examination.
Measured: Week 96
Brain MRI safety
Clinically significant new MRI findings. Proportion of participants with new clinically significant MRI findings (e.g., edema, hemorrhage) vs Baseline.
Measured: At week 96
Suicidality (C-SSRS)
Suicidal ideation or behavior (C-SSRS). Proportion of participants with any positive suicidal ideation or behavior signal on the C-SSRS.
Measured: Week 96
Laboratory safety
Treatment-emergent hematology and biochemistry abnormalities:
- Proportion of participants with ≥1 treatment-emergent hematology abnormality meeting predefined thresholds (e.g., CTCAE grade ≥2).
- Proportion of participants with ≥1 treatment-emergent biochemistry abnormality meeting predefined thresholds (e.g., CTCAE grade ≥2).
Measured: At week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2025
- Study start22 Dec 2025 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación de Investigación Biomédica - Hospital Universitario de La Princesa, Hospital Universitario Marqués de Valdecilla, Fundación CITA Alzheimer, University Hospital Virgen de las Nieves
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07234695
- Sponsor's protocol ID
- IIBSP-LEV-2024-86
- Other IDs
- 2024-516148-24-00
- Acronym
- LESS-AD
- Status last verified
- Dec 2025
- First submitted
- 2 Oct 2025
- Last updated
- 12 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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).
- ClinicalTrials.gov ID
- NCT07234695
- Acronym / sponsor ID
- LESS-AD / IIBSP-LEV-2024-86
- Conditions
- Down Syndrome, Down Syndrome (DS), Down Syndrome (Trisomy 21), Alzheimer Dementia, Alzheimer Dementia (AD), Alzheimer Disease
- Keywords
- Down syndrome, epilepsy, Alzheimer, dementia, levetiracetam, prevention, placebo-controlled, epileptic seizures
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Collaborators
- Fundación de Investigación Biomédica - Hospital Universitario de La Princesa, Hospital Universitario Marqués de Valdecilla, Fundación CITA Alzheimer, University Hospital Virgen de las Nieves
- Study start
- 22 Dec 2025 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 18 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To quantify the time to the first bilateral tonic-clonic seizure between groups (levetiracetam vs. placebo).
- To evaluate the incidence of mortality between groups (levetiracetam vs. placebo).
- To study changes in biomarkers related to Alzheimer's disease:
- Functional changes (CAMDEX-DS)
- Cognitive changes (CAMCOG, mCRT)
- Plasma biomarkers (217-pTau, NfL)
- Brain structure (cortical thickness, hippocampal volume, gray matter volume)
- Epileptiform activity (EEG)
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Levetiracetam 500 mg/12h | Experimental | Drug: Levetiracetam 500mgTablets 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. |
| Placebo | Placebo comparator | Drug: PlaceboTablets for twice daily administration for 96 weeks. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Levetiracetam 500mgUse of Levetiracetam to prevent Seizures in Symptomatic Alzheimer's Disease in adults with Down syndrome (the LESS-AD trial) | Drug | Levetiracetam 500 mg/12h |
| PlaceboComparator | Drug | Placebo |
Primary outcome
Efficacy of Levetiracetam as a preventive treatment for epileptic seizures in adults with Alzheimer's disease associated with Down syndrome.
Time frame: From enrollment to the end of treatment at 96 weeks
Number (percentage) of subjects who do not develop a bilateral tonic-clonic epileptic seizure during the study treatment phase (96 weeks).
24 secondary outcomes
Time to first bilateral tonic-clonic epileptic seizure
Time frame: days
All-cause mortality
Time frame: percentage
Time to death
Time frame: days
Cognition
Time frame: CAMCOG-DS: change from baseline and week 96.
Plasma biomarkers -217p-tau
Time frame: Change from baseline and week 96
Plasma biomarkers- NfL
Time frame: At week 96
Neuroimaging GMV
Time frame: At week 96
Neuroimaging- HV
Time frame: Change at week 96
Neuroimaging- LVV
Time frame: Week 96
Neuroimaging CTh
Time frame: Week 96
Electroencephalography (EEG)
Time frame: At week 96.
EEG- band power
Time frame: At week 96
EEG sync
Time frame: At week 96
Safety of Levetiracetam
Time frame: From enrollment to the end of treatment at 96 weeks
Incidence of adverse events (AEs)
Time frame: At week 96
AEs- TEAE rate
Time frame: Up to week 36
Maximum AE severity
Time frame: At week 96
AEs- Dose interruptions
Time frame: At week 96.
Vital signs- BP
Time frame: At week 96
Vital signs- HR
Time frame: At week 96
Physical examination
Time frame: Week 96
Brain MRI safety
Time frame: At week 96
Suicidality (C-SSRS)
Time frame: Week 96
Laboratory safety
Time frame: At week 96
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Diego Real de Asúa Cruzat, Doctor contact
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Levetiracetam 500mg in people with Down Syndrome and Down Syndrome (DS), run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 5 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact María Carmona Iragui, Doctor (+34 93 556 59 56, mcarmonai@santpau.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy of Levetiracetam as a preventive treatment for epileptic seizures in adults with Alzheimer's disease associated with Down syndrome. (time frame: From enrollment to the end of treatment at 96 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2026.