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

NCT01044758 | Completed Phase 2 Results DMC

• 2 other identifiers: NA_00030573RC2AG036419
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

Primary Outcomes (1)

• Brain Activity in the Dentate Gyrus / CA3 Subregion of the Hippocampus Measured With Blood Oxygenation Level Dependent (BOLD) Functional MRI

  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 Outcomes (1)

• Behavioral Performance as Assessed in the Functional Magnetic Resonance Imaging (fMRI) Memory Task

  2 weeks

Study Arms (7)

aMCI_62.5mg drug first, then placebo

EXPERIMENTAL

Amnestic MCI: 62.5mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)

Drug: Levetiracetam 62.5mg; Drug: Placebo

aMCI_Placebo first, then 62.5mg drug

EXPERIMENTAL

Amnestic MCI: Placebo capsule twice daily (two weeks), washout (4 weeks), and 62.5mg levetiracetam twice daily (two weeks)

Drug: Levetiracetam 62.5mg; Drug: Placebo

aMCI_125mg drug first, then placebo

EXPERIMENTAL

Amnestic MCI: 125mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)

Drug: Levetiracetam 125mg; Drug: Placebo

aMCI_Placebo first, then 125mg drug

EXPERIMENTAL

Amnestic MCI: Placebo capsule twice daily (two weeks), washout (4 weeks), and 125mg levetiracetam twice daily (two weeks)

Drug: Levetiracetam 125mg; Drug: Placebo

aMCI_250mg drug first, then placebo

EXPERIMENTAL

Amnestic MCI: 250mg levetiracetam twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)

Drug: Levetiracetam 250mg; Drug: Placebo

aMCI_Placebo first, then 250mg drug

EXPERIMENTAL

Amnestic MCI: Placebo capsule twice daily (two weeks), washout (4 weeks), and 250mg levetiracetam twice daily (two weeks)

Drug: Levetiracetam 250mg; Drug: Placebo

Control_Placebo first, then placebo

PLACEBO COMPARATOR

Healthy control: placebo capsule twice daily (two weeks), washout (4 weeks), and placebo capsule twice daily (two weeks)

Drug: Placebo

Interventions

Levetiracetam 62.5mg DRUG

62.5mg twice daily (2 weeks)

Also known as: Keppra

aMCI_62.5mg drug first, then placebo; aMCI_Placebo first, then 62.5mg drug

Levetiracetam 125mg DRUG

125mg twice daily (2 weeks)

Also known as: Keppra

aMCI_125mg drug first, then placebo; aMCI_Placebo first, then 125mg drug

Levetiracetam 250mg DRUG

250mg twice daily (2 weeks)

Also known as: Keppra

aMCI_250mg drug first, then placebo; aMCI_Placebo first, then 250mg drug

Placebo DRUG

placebo capsule twice daily (2 weeks)

Control_Placebo first, then placebo; aMCI_125mg drug first, then placebo; aMCI_250mg drug first, then placebo; aMCI_62.5mg drug first, then placebo; aMCI_Placebo first, then 125mg drug; aMCI_Placebo first, then 250mg drug; aMCI_Placebo first, then 62.5mg drug

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Related Publications (7)

• 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.

  PMID: 18802001 BACKGROUND

• 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.

  PMID: 18356518 BACKGROUND

• 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. doi: 10.1016/j.neuron.2007.07.025.

  PMID: 17785178 BACKGROUND

• 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. doi: 10.1073/pnas.012467899. Epub 2001 Dec 26.

  PMID: 11756667 BACKGROUND

• 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. doi: 10.1523/JNEUROSCI.1744-05.2005.

  PMID: 16033897 BACKGROUND

• Wilson IA, Gallagher M, Eichenbaum H, Tanila H. Neurocognitive aging: prior memories hinder new hippocampal encoding. Trends Neurosci. 2006 Dec;29(12):662-70. doi: 10.1016/j.tins.2006.10.002. Epub 2006 Oct 13.

  PMID: 17046075 BACKGROUND

• 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.

  PMID: 20032967 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Memory Disorders; Alzheimer Disease

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gregory Krauss, M.D.
• Organization: Johns Hopkins University School of Medicine

gkrauss@jhmi.edu

(410) 955-2822

Study Officials

• Gregory L Krauss, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2010
• First Posted: January 8, 2010
• Study Start: December 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: August 21, 2017
• Results First Posted: August 21, 2017

Record last verified: 2017-07

Locations

US (1)