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

This study has been completed.
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01044758
First received: January 7, 2010
Last updated: July 19, 2017
Last verified: July 2017
  Purpose
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).

Condition Intervention Phase
Mild Cognitive Impairment (MCI) Drug: Levetiracetam 62.5mg Drug: Levetiracetam 125mg Drug: Levetiracetam 250mg Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Bridging Cognitive Aging in Rodents to Man Using fMRI in Amnestic MCI

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 96
Study Start Date: December 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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: Levetiracetam 125mg
125mg twice daily (2 weeks)
Other Name: Keppra
Drug: Placebo
placebo capsule twice daily (2 weeks)
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: Levetiracetam 125mg
125mg twice daily (2 weeks)
Other Name: Keppra
Drug: Placebo
placebo capsule twice daily (2 weeks)
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: Levetiracetam 250mg
250mg twice daily (2 weeks)
Other Name: Keppra
Drug: Placebo
placebo capsule twice daily (2 weeks)
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: Levetiracetam 250mg
250mg twice daily (2 weeks)
Other Name: Keppra
Drug: Placebo
placebo capsule twice daily (2 weeks)
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)

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

Ages Eligible for Study:   50 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01044758

Locations
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
National Institute on Aging (NIA)
Investigators
Principal Investigator: Gregory L Krauss, MD Johns Hopkins University
  More Information

Publications:

Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01044758     History of Changes
Other Study ID Numbers: NA_00030573
RC2AG036419 ( U.S. NIH Grant/Contract )
Study First Received: January 7, 2010
Results First Received: September 8, 2014
Last Updated: July 19, 2017

Keywords provided by Johns Hopkins University:
Mild Cognitive Impairment
Amnestic Mild Cognitive Impairment
Functional Magnetic Resonance Imaging
Levetiracetam
Keppra
Medial Temporal Lobe
Memory Impairment
Alzheimer's Disease
AD

Additional relevant MeSH terms:
Cognition Disorders
Mild Cognitive Impairment
Neurocognitive Disorders
Mental Disorders
Etiracetam
Piracetam
Anticonvulsants
Nootropic Agents
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 21, 2017