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

Mild Cognitive Impairment (MCI) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01044758
• Other study ID #: RC2AG036419
• Secondary ID: RC2AG036419
• Status: Completed
• Phase: Phase 2
• First received: January 7, 2010
• Last updated: August 30, 2012
• Start date: December 2009
• Est. completion date: July 2012

Study information

• Verified date: August 2012
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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 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. We 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years to 85 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cognition Disorders
• Mild Cognitive Impairment
• Mild Cognitive Impairment (MCI)

Intervention

Drug:
• Levetiracetam
50mg - 500 mg twice a day for two weeks.
• Placebo
placebo capsule twice a day for two weeks
• Placebo
placebo capsule twice daily for four weeks

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (7)

Bakker A, Kirwan CB, Miller M, Stark CE. Pattern separation in the human hippocampal CA3 and dentate gyrus. Science. 2008 Mar 21;319(5870):1640-2. doi: 10.1126/science.1152882. — View Citation

Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold KH, Haass C, Staufenbiel M, Konnerth A, Garaschuk O. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease. Science. 2008 Sep 19;321(5896):1686-9. doi: 10.1126/science.1162844. — View Citation

Koh MT, Haberman RP, Foti S, McCown TJ, Gallagher M. Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment. Neuropsychopharmacology. 2010 Mar;35(4):1016-25. doi: 10.1038/npp.2009.207. Epub 2009 Dec 23. — View Citation

Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron. 2007 Sep 6;55(5):697-711. — View Citation

Sperling R, Greve D, Dale A, Killiany R, Holmes J, Rosas HD, Cocchiarella A, Firth P, Rosen B, Lake S, Lange N, Routledge C, Albert M. Functional MRI detection of pharmacologically induced memory impairment. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):455-60. Epub 2001 Dec 26. — View Citation

Wilson IA, Gallagher M, Eichenbaum H, Tanila H. Neurocognitive aging: prior memories hinder new hippocampal encoding. Trends Neurosci. 2006 Dec;29(12):662-70. Epub 2006 Oct 13. Review. — View Citation

Wilson IA, Ikonen S, Gallagher M, Eichenbaum H, Tanila H. Age-associated alterations of hippocampal place cells are subregion specific. J Neurosci. 2005 Jul 20;25(29):6877-86. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	fMRI activation in medial temporal lobe regions		2 weeks	No
Secondary	Memory performance as assessed in the post-scan procedure and in the neuropsychological test battery		2 weeks	No