← Trials/Trial dossier/NCT03875638

LeAD

CompletedPhase 2

Treating Hyperexcitability in AD With Levetiracetam

Treating Hyperexcitability in Alzheimer's Disease With Levetiracetam to Improve Brain Function and Cognition

Lead sponsor

Beth Israel Deaconess Medical Center

Asset

Levetiracetam

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•Alzheimer's disease•Amyloid biomarker required (PET)•MMSE ≥20•AD symptomatic therapy: stable

Primary endpoints

•Neuropsychological Test Battery (NTB)•Transcranial magnetic stimulation (TMS) resting motor threshold•Transcranial magnetic stimulation (TMS)-evoked electroencephalogram (EEG)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID2019P000091

NCT IDNCT03875638

Timeline

Milestones

Study first posted2019-03-15actual

Study start2019-08-22actual

Primary completion2026-02-16actual

Study completion2026-02-16actual

Last update posted2026-04-07actual

Assets

Drug assets

Levetiracetam

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age50 Years

Maximum age90 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

Inclusion Criteria for the Subjects with early Alzheimer's Disease (AD)

•Age 50-90 years old.

•On a stable dose of medications for memory loss including cholinesterase inhibitors (for example: donepezil, rivastigmine or memantine) as defined by 4 consecutive weeks of treatment at an unchanging dose

•Meeting the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD.

•Mini Mental State Examination (MMSE) ≥ 20.

•Positive amyloid status (as defined by cerebral spinal fluid biomarkers or amyloid positron emission tomography (PET) study.

•Clinician Dementia Rating (CDR) of 0.5-1.0.

Inclusion Criteria for Healthy Control Subjects

•Age 50-90 years old.

•Normal neurologic exam

•Mini Mental State Examination (MMSE) > 28

•Clinician Dementia Rating (CDR) of 0

Exclusion criteria

Exclusion Criteria Subjects with early Alzheimer's Disease

•Diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist. Evidence of epileptiform discharges and electroencephalogram (EEG) abnormalities will be included;

•Current or past history of any neurological disorder other than dementia, such as epilepsy, stroke (cortical stroke), progressive neurologic disease (e.g. multiple sclerosis) or intracranial brain lesions; and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment. Non-cortical disease such as scattered white matter changes (including lacunar infarcts < 1 cm) and asymptomatic, subacute, cerebellar infarcts may be included upon review of a medically responsible neurologist. However, subjects with significant vascular disease, as defined by a score greater than 2 on the age-related white matter changes (ARWMC) scale, will be excluded.

•Any current diagnosis of a major psychiatric disorder (e.g., schizophrenia, bipolar disorder) with the exception of depression. As co-morbidity of anxiety / depression in AD is high, anxiety / depression will not be an automatic exclusion. However, the study physician will assess any subject with a Geriatric Depression Score (GDS) score of 9 or above, and will exclude subjects with a past history of multiple psychiatric hospitalizations or suicide attempts, or current active suicidality.

•Evidence of significant kidney impairment as defined as an estimated glomerular filtration rate (eGFR) <30

•Medications will be reviewed by the responsible covering physician and a decision about inclusion will be made based on the participant's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other central nervous system active drugs. Current use of an antiepileptic drug will be an absolute exclusion.

Exclusion Criteria Healthy Control Subjects

•History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist.

•Current or past history of any neurological disorder, such as epilepsy, stroke (cortical stroke), progressive neurologic disease (e.g. multiple sclerosis) or intracranial brain lesions; and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment.

•Any current diagnosis of a major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depressive disorder).

•Abnormal Neurologic or Cognitive exam

•Use of medications that could alter cortical excitability, as determined by the investigators.

Exclusion Criteria for All Subjects regarding magnetic resonance imaging (MRI) and transcranial magnetic stimulation (TMS)

•History of head trauma resulting in prolonged loss of consciousness.

•Current history of poorly controlled headaches including chronic medication for migraine prevention.

•History of fainting spells of unknown or undetermined etiology that might constitute seizures.

•Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.).

•Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering MD (e.g. MRI compatible joint replacement).

•Any devices such as pacemaker, medication pump, nerve stimulator, ventriculo-peritoneal shunt unless cleared by the responsible covering physician.

•Substance use disorders within the past six months.

Endpoints (12)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Fluid / digital biomarkers

Other (unclassified)

Neuroimaging

Global cognition

1 endpoint

Primary/protocol endpoint

Neuropsychological Test Battery (NTB)

Time frame:From enrollment until the end of the treatment periods at 5 months

descriptive

Neuroimaging

2 endpoints

Primary/protocol endpoint

Resting-state electroencephalogram (EEG) beta band connectivity

Time frame:From enrollment until the end of the treatment periods at 5 months

descriptive

Primary/protocol endpoint

Default-mode network resting-state functional magnetic resonance imaging (fMRI) functional connectivity

Time frame:From enrollment until the end of the treatment periods at 5 months

descriptive

Fluid / digital biomarkers

6 endpoints

Primary/protocol endpoint

Transcranial magnetic stimulation (TMS)-evoked electroencephalogram (EEG) hypersynchrony

Time frame:From enrollment until the end of the treatment periods at 5 months

descriptive

Primary/protocol endpoint

Resting-state electroencephalogram (EEG) beta band power

Time frame:From enrollment until the end of the treatment periods at 5 months

descriptive

Primary/protocol endpoint

Change in beta power after theta-burst stimulation

Time frame:From enrollment until the end of the treatment periods at 5 months

change from baseline, improvement

Other/protocol endpoint

Transcranial magnetic stimulation (TMS)-evoked N45 electroencephalogram (EEG) potential

Time frame:From enrollment until the end of the treatment periods at 5 months

change from baseline, improvement

Other/protocol endpoint

Interictal Epileptiform Discharges

Time frame:Baseline

descriptive

Other/protocol endpoint

Baseline TMS-EEG Parietal Cortical Excitability

Time frame:Baseline

descriptive

Other (unclassified)

3 endpoints

Primary/protocol endpoint/low confidence

Transcranial magnetic stimulation (TMS) resting motor threshold

Time frame:From enrollment until the end of the treatment periods at 5 months

change from baseline, improvement

Primary/protocol endpoint/low confidence

Change in motor evoked potential (MEP) amplitude

Time frame:From enrollment until the end of the treatment periods at 5 months

change from baseline, improvement

Other/protocol endpoint/low confidence

Baseline motor cortical hyperexcitability

Time frame:Baseline

descriptive

Publications (2)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.