Levetiracetam and Memory Function in Amnestic Mild Cognitive Impairment (MCI)

July 19, 2017 updated by: Johns Hopkins University

Bridging Cognitive Aging in Rodents to Man Using fMRI in Amnestic MCI

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

96

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years to 83 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: aMCI_62.5mg drug first, then placebo

Amnestic MCI:

62.5mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)
Drug: Levetiracetam 62.5mg
62.5mg twice daily (2 weeks)
Other Names:
  • Keppra
Drug: Placebo
placebo capsule twice daily (2 weeks)
Experimental: aMCI_Placebo first, then 62.5mg drug

Amnestic MCI:

Placebo capsule twice daily (two weeks), washout (4 weeks), and 62.5mg levetiracetam twice daily (two weeks)
Drug: Levetiracetam 62.5mg
62.5mg twice daily (2 weeks)
Other Names:
  • Keppra
Drug: Placebo
placebo capsule twice daily (2 weeks)
Experimental: aMCI_125mg drug first, then placebo

Amnestic MCI:

125mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)
Drug: Placebo
placebo capsule twice daily (2 weeks)
Drug: Levetiracetam 125mg
125mg twice daily (2 weeks)
Other Names:
  • Keppra
Experimental: aMCI_Placebo first, then 125mg drug

Amnestic MCI:

Placebo capsule twice daily (two weeks), washout (4 weeks), and 125mg levetiracetam twice daily (two weeks)
Drug: Placebo
placebo capsule twice daily (2 weeks)
Drug: Levetiracetam 125mg
125mg twice daily (2 weeks)
Other Names:
  • Keppra
Experimental: aMCI_250mg drug first, then placebo
Amnestic MCI: 250mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)
Drug: Placebo
placebo capsule twice daily (2 weeks)
Drug: Levetiracetam 250mg
250mg twice daily (2 weeks)
Other Names:
  • Keppra
Experimental: aMCI_Placebo first, then 250mg drug

Amnestic MCI:

Placebo capsule twice daily (two weeks), washout (4 weeks), and 250mg levetiracetam twice daily (two weeks)
Drug: Placebo
placebo capsule twice daily (2 weeks)
Drug: Levetiracetam 250mg
250mg twice daily (2 weeks)
Other Names:
  • Keppra
Placebo Comparator: Control_Placebo first, then placebo

Healthy control:

placebo capsule twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)
Drug: Placebo
placebo capsule twice daily (2 weeks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain Activity in the Dentate Gyrus / CA3 Subregion of the Hippocampus Measured With Blood Oxygenation Level Dependent (BOLD) Functional MRI
Time Frame: 2 weeks
Measurement of average brain activity in the dentate gyrus / CA3 subregion of the hippocampus measured with BOLD functional MRI in patients with mild cognitive impairment on placebo and on drug compared to average brain activity in this brain area in control subjects.
2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Behavioral Performance as Assessed in the Functional Magnetic Resonance Imaging (fMRI) Memory Task
Time Frame: 2 weeks
Mnemonic similarity task which assesses long term memory function. Scale ranges from 0-100 with higher scores indicating better memory performance.
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Gregory L Krauss, MD, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

July 1, 2012

Study Completion (Actual)

July 1, 2012

Study Registration Dates

First Submitted

January 7, 2010

First Submitted That Met QC Criteria

January 7, 2010

First Posted (Estimate)

January 8, 2010

Study Record Updates

Last Update Posted (Actual)

August 21, 2017

Last Update Submitted That Met QC Criteria

July 19, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NA_00030573
  • RC2AG036419 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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