Clinical trial NCT01044758: Levetiracetam and Memory Function in Amnestic Mild Cognitive Impairment (MCI)
Official title: Bridging Cognitive Aging in Rodents to Man Using fMRI in Amnestic MCI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2010-01-08
Enrollment: 96
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* All: English as a first language; right handed; able to complete written informed consent.
* MCI subjects: In addition to above, must meet criteria for amnestic Mild Cognitive Impairment (MCI). This includes a memory complaint corroborated by an informant; impaired memory function for age and educational level; preserved general cognitive function; intact abilities of daily living; no clinical dementia.
* Age matched Controls: Must have memory and cognitive status that is normal for their age.

Exclusion Criteria:

* Familial Alzheimer's Disease (AD) due to known genetic mutations
* AD with Parkinsonian features; major psychiatric or behavioral disorders (e.g. depression, agitation, psychosis, manic-depressive disorder)
* Primary or metastatic intracranial neoplasm
* History of severe head trauma
* Intra-cerebral hemorrhage
* Seizure disorder
* Hemispheric stroke
* Presence of a progressive central nervous system disease
* Presence of lacunar infarcts
* Medical contraindications to MRI including cardiac pacemaker, presence of intraocular or intracranial metallic objects
* Any known allergy to levetiracetam or behavioral problems that are a contraindication to taking Levetiracetam (e.g. agitation)
* Prescribed use of anti-seizure medications.

Primary outcomes:
measure: Brain Activity in the Dentate Gyrus / CA3 Subregion of the Hippocampus Measured With Blood Oxygenation Level Dependent (BOLD) Functional MRI
timeFrame: 2 weeks
Secondary outcomes:
measure: Behavioral Performance as Assessed in the Functional Magnetic Resonance Imaging (fMRI) Memory Task
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Gregory L Krauss, MD
role: PRINCIPAL_INVESTIGATOR
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