Clinical trial NCT01044758
Conditions: Mild Cognitive Impairment (MCI)
Keywords: Mild Cognitive Impairment Amnestic Mild Cognitive Impairment Functional Magnetic Resonance Imaging Levetiracetam Keppra Medial Temporal Lobe Memory Impairment Alzheimer's Disease AD
Sponsor: Johns Hopkins University
Start date: 2009-12-01; Completion date: 2012-07-01
Enrollment: 96 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This research is being done to find out if daily use of the drug levetiracetam can improve memory function in individuals with memory problems like those associated with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD).

Detailed description:
Increasing research is focused on conditions that precede the clinical diagnosis of Alzheimer's disease (AD) in order to detect patients at risk for early intervention. One such condition is mild cognitive impairment (MCI). Functional magnetic resonance imaging (fMRI) studies in this group of patients have reported increased activation in the Medial Temporal Lobe (MTL) during performance of memory tasks. The functional significance of increased activation is unclear. One possibility is that greater activity reflects the increased effort needed in order to maintain performance, and as such would be a compensatory response. An alternative possibility is that increased activation reflects aberrant physiology related to the disease process itself and as such would be a sign of greater underlying disease severity and would interfere with brain function.

Data in animal models suggest the possibility that low dose levetiracetam (well-tolerated anti-convulsant) treatment may reduce the observed hyperactivity and improve memory performance among individuals with MCI. The investigators are therefore conducting a within-subjects trial of 8 weeks duration, involving 144 subjects and low dose treatment with levetiracetam. During the course of the study, each subject may receive both drug and placebo for two weeks, with the order of administering those treatments counterbalanced. Cognitive testing and fMRI imaging will be obtained after 2-weeks on drug/placebo. The overall goal of the study is to determine if treatment of MCI subjects with low dose levetiracetam reduces hyperactivity within the MTL and improves memory performance.

Arms: arm 1: Amnestic MCI:

62.5mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks) arm 2: Amnestic MCI:

Placebo capsule twice daily (two weeks), washout (4 weeks), and 62.5mg levetiracetam twice daily (two weeks) arm 3: Amnestic MCI:

125mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks) arm 4: Amnestic MCI:

Placebo capsule twice daily (two weeks), washout (4 weeks), and 125mg levetiracetam twice daily (two weeks) arm 5: Amnestic MCI: 250mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks) arm 6: Amnestic MCI:

Placebo capsule twice daily (two weeks), washout (4 weeks), and 250mg levetiracetam twice daily (two weeks) arm 7: Healthy control:

placebo capsule twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)
Interventions: intervention 1: Levetiracetam 62.5mg intervention 2: Levetiracetam 125mg intervention 3: Levetiracetam 250mg intervention 4: Placebo
Intervention descriptions: intervention 1: 62.5mg twice daily (2 weeks) intervention 2: 125mg twice daily (2 weeks) intervention 3: 250mg twice daily (2 weeks) intervention 4: placebo capsule twice daily (2 weeks)

Protocol documents: