Treating Hyperexcitability in AD With Levetiracetam

Launched by BETH ISRAEL DEACONESS MEDICAL CENTER · Mar 13, 2019

Keywords

ClinConnect Summary

This clinical trial is studying the effects of a medication called levetiracetam (LEV) on individuals with early Alzheimer's Disease (AD). Researchers want to understand if this medication can help improve brain function and cognitive abilities in patients who experience increased brain activity, known as cortical hyperexcitability. The trial is currently looking for participants aged 50 to 90 who have early-stage Alzheimer's and are on stable memory medications. Healthy individuals in the same age range can also participate as control subjects, helping researchers compare results.

If you or a loved one is eligible and chooses to participate, you can expect to undergo some assessments to check memory and brain function. Participants will be monitored throughout the study to see if taking levetiracetam helps improve cognitive symptoms associated with Alzheimer’s. This trial aims to provide valuable insights into how this medication might change brain activity in patients with Alzheimer's, potentially leading to better treatment options in the future.

Gender

ALL

Eligibility criteria

• 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.