Levetiracetam and Memory Function in Amnestic Mild Cognitive Impairment (MCI)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01044758 |
Recruitment Status :
Completed
First Posted : January 8, 2010
Results First Posted : August 21, 2017
Last Update Posted : August 21, 2017
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Mild Cognitive Impairment (MCI) | Drug: Levetiracetam 62.5mg Drug: Levetiracetam 125mg Drug: Levetiracetam 250mg Drug: Placebo | Phase 2 |
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 (Clinical Trial) |
Actual Enrollment : | 96 participants |
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 |
Study Start Date : | December 2009 |
Actual Primary Completion Date : | July 2012 |
Actual Study Completion Date : | July 2012 |

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 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) |
- 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.
- 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.

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, Learn About Clinical Studies.
Ages Eligible for Study: | 50 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01044758
United States, Maryland | |
Johns Hopkins University School of Medicine | |
Baltimore, Maryland, United States, 21287 |
Principal Investigator: | Gregory L Krauss, MD | Johns Hopkins University |
Responsible Party: | Johns Hopkins University |
ClinicalTrials.gov Identifier: | NCT01044758 |
Other Study ID Numbers: |
NA_00030573 RC2AG036419 ( U.S. NIH Grant/Contract ) |
First Posted: | January 8, 2010 Key Record Dates |
Results First Posted: | August 21, 2017 |
Last Update Posted: | August 21, 2017 |
Last Verified: | July 2017 |
Mild Cognitive Impairment Amnestic Mild Cognitive Impairment Functional Magnetic Resonance Imaging Levetiracetam Keppra |
Medial Temporal Lobe Memory Impairment Alzheimer's Disease AD |
Cognitive Dysfunction Cognition Disorders Neurocognitive Disorders Mental Disorders |
Levetiracetam Anticonvulsants Nootropic Agents |