NCT03875638

Treating Hyperexcitability in AD With Levetiracetam

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 58 (actual)
• Sponsor: Beth Israel Deaconess Medical Center · Academic / Other
• Sex: All
• Age: 50 Years – 90 Years
• Healthy volunteers: Accepted

Summary

The aim of this study is to explore the relationship between cortical hyperexcitability, abnormalities of brain network function, and cognitive dysfunction in human patients with AD and whether administration of the antiepileptic medication levetiracetam (LEV) normalizes these measures and improves cognition.

Detailed description

This is a randomized, placebo-controlled crossover study. Participants with early Alzheimer's Disease (AD) will be tested in a double-blind crossover design with placebo, low-dose levetiracetam (LEV) 125 mg twice daily or high-dose LEV 500mg twice daily. These results will be contrasted with results from a demographically similar control group who will undergo baseline testing only, without any intervention, to establish a comparison norm for the AD group. Each subject will undergo four screening and baseline visits consisting of a baseline neurological, medical, and cognitive evaluation. If amyloid status is unknown in AD patients, the participant will have an amyloid PET scan. Additional baseline measures include: a high density electroencephalogram (EEG); a 24 hour ambulatory EEG; functional magnetic resonance imaging (fMRI); neuropsychological testing; and transcranial magnetic stimulation with electromyogram (EMG) and EEG measures to assess cortical excitability. AD participants will be randomized to one of six possible groups that consists of a varying order of 3 treatment periods (LEV 125 mg, LEV 500 mg and placebo). The group assignments will be counterbalanced across subjects. Each treatment period will last for 4 weeks with a 4 week washout between treatments. All participants will be assessed prior to initiation of a treatment period (with the initial assessment occurring as part of the baseline assessment) and at the end of each treatment period. The following measures will be repeated as done at baseline at these time points: fMRI; neuropsychological testing; and TMS-EMG-EEG. AD participants will be enrolled for approximately 5 months.

Conditions

• Alzheimer Dementia
• Alzheimer Disease
• Dementia of Alzheimer Type
• Mild Cognitive Impairment

Interventions

Type	Name	Description
DRUG	Levetiracetam	Levetiracetam is an antiepileptic medication that has been shown to reduced network cortical hyperexcitability
DRUG	Placebo oral capsule	The placebo is a capsule that is identical in appearance to the levetiracetam

Timeline

• Start date: 2019-08-22
• Primary completion: 2026-02-16
• Completion: 2026-02-16
• First posted: 2019-03-15
• Last updated: 2026-04-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study