Levetiracetam for Alzheimer's Disease Neuropsychiatric Symptoms Related to Epilepsy Trial (LAPSE) (LAPSE)

June 27, 2019 updated by: Walter Reed National Military Medical Center

Levetiracetam for Alzheimer's Disease Neuropsychiatric Symptoms Related to Epilepsy Trial (LAPSE) - A Phase II Exploratory Study

Patients with Alzheimer's disease (AD) are increasingly recognized to have seizures in addition to cognitive decline. Seizures may contribute to memory problems as well as other symptoms common in AD like agitation, depression, or apathy. These symptoms are collectively called neuro-psychiatric symptoms. Studies of magnetic resonance imaging (MRI) in patients with AD have suggested that injury to certain parts of the brain can cause these neuro-psychiatric symptoms. Based on this evidence, the investigators hypothesize that seizures can also cause neuro-psychiatric symptoms in patients with AD and may be related to the injury seen on MRI.

The current study will follow participants for 1 year and will involve participants with AD who also have neuro-psychiatric symptoms. Participants will be examined with three brain wave studies to assess for seizure-like activity. Participants with seizure-like activity will all receive levetiracetam for 1 year. All participants will have their neuro-psychiatric symptoms, cognitive abilities, quality of life, and AD severity assessed throughout the year. The investigators plan to determine if levetiracetam changes the severity of the participants' neuro-psychiatric symptoms compared to their baseline as well as compared to participants without seizure-like activity. 65 participants will need to be recruited to test the study hypotheses. The study will take place at Walter Reed National Military Medical Center.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Alzheimer's Disease (AD) has long been known to carry an increased risk of seizure, with early estimates suggesting patients with AD have a 10-22% risk at least one unprovoked seizure and an 8- to 10-fold higher seizure rate over the general population. Retrospective data has suggested that the onset of both clinical seizure and abnormal discharge on electroencephalogram (EEG) may cluster around or even precede the onset of cognitive decline. With extended EEG and/or 1-hour magnetoencephalogram (MEG), up to 42% of patients with AD have evidence of subclinical seizure or epileptiform discharges, two-thirds of which were identified only during sleep. Recent evidence has also found a much higher incidence of dyscognitive seizure (47%) and other nonconvulsive semiologies (55%) than previously reported, including jamais vu, déjà vu, sensory phenomenon, speech arrest/aphasia, and amnestic spells.

A particularly problematic aspect of dementia in general and AD in particular is neuropsychiatric symptoms. Neuropsychiatric symptoms increase with duration and severity of dementia, observed in as much as 60-90% of these patients. To some extent, neuropsychiatric symptoms may also be associated with focal dysfunction, particularly of the non-dominant fronto-temporal lobes. Seizure or transient epileptiform discharges, then, might explain some of the neuropsychiatric manifestations associated with AD, especially since the most common areas of discharge are the fronto-temporal lobes in AD. Neuropsychiatric symptoms and their causes are of particular concern in the management of patients with AD given the strain on patients and families and their high association with nursing home placement.

This study will complete up to 3 serial EEGs on each participant, and all participants with epileptiform activity identified on EEG will be started on levetiracetam. All participants will be followed with serial neuro-psychiatric symptom, cognitive, severity, and quality-of-life metrics in order to analyze the effect of levetiracetam on these measures over 1 year.

Study Type

Interventional

Enrollment (Anticipated)

65

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 Contact

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20889
        • Walter Reed National Military Medical Center
        • Contact:
        • Principal Investigator:
          • Timothy R Malone, MD
        • Sub-Investigator:
          • Margaret Swanberg, MD
        • Sub-Investigator:
          • Joseph V Brown, MD
        • Sub-Investigator:
          • Adriana Martinez, MSc
        • Sub-Investigator:
          • Tuamokumo Francois, PhD

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Meet the National Institute of Aging-Alzheimer's Association criteria for probable AD
  • Twelve-item Neuropsychiatric Inventory with score 4 or greater
  • MMSE <26
  • Stable doses current medications, including acetylcholinesterase inhibitors if applicable, for at least 4 weeks prior to trial entry
  • Reliable caregiver willing and available to assist with medication administration, outcome measures
  • MRI completed with no evidence of potential seizure focus as outlined in the exclusion criteria

Exclusion Criteria:

  • Imaging suggestive of potential seizure focus or alternative cause of dementia
  • Previous Epilepsy diagnosis
  • Use of anti-epileptic medication for any indication within previous three months
  • History of head trauma with loss of consciousness more than 30 minutes
  • Alcohol/Substance abuse within 5 years of dementia onset or previous 5 years
  • History of Korsakoff's syndrome
  • History of encephalitis/meningitis
  • Female participant who is pregnant, lactating or planning pregnancy during trial
  • Scheduled elective surgery or other procedures requiring general anesthesia during the trial
  • Participant with life expectancy of less than 12 months
  • Any cancer requiring current chemotherapy
  • Known allergy or history of previous adverse reaction to levetiracetam
  • Major depression or other significant behavioral disturbance preceding Alzheimer's Disease diagnosis
  • Enrollment in another clinical treatment trial
  • Laboratory evidence of an alternative cause of dementia or which might preclude treatment, including untreated vitamin B12 deficiency, untreated hypothyroidism, syphilis, positive human immunodeficiency virus testing, end-stage renal disease on dialysis, significant renal impairment (creatinine clearance <75 ml/minute), or liver function tests >2x upper limit of normal within the preceding three months

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: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Levetiracetam
All patients with epileptiform activity on initial screening EEG will receive levetiracetam for 1 year
Drug: Levetiracetam
Levetiracetam 500mg twice a day
Other Names:
  • Keppra

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Neuropsychiatric Inventory Score (NPI)
Time Frame: Assessed at enrollment, week 7, week 15, week 27, and month 12
Neuropsychiatric Symptom Metric
Assessed at enrollment, week 7, week 15, week 27, and month 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Clinical Dementia Rating Sum of Boxes (CDR-SOB)
Time Frame: Assessed at enrollment, week 7, week 15, week 27, and month 12
Patient/Informant AD Severity Metric
Assessed at enrollment, week 7, week 15, week 27, and month 12
Change in Alzheimer's Disease Cooperative study - Clinical Global Impression of Change (ADCS-CGIC)
Time Frame: Assessed at enrollment, week 7, week 15, week 27, and month 12
Clinician AD Severity Metric
Assessed at enrollment, week 7, week 15, week 27, and month 12
Change in EuroQol 5-Dimension (EQ-5D)
Time Frame: Assessed at enrollment, week 7, week 15, week 27, and month 12
Quality of Life Metric
Assessed at enrollment, week 7, week 15, week 27, and month 12
Change in Mini-Mental State Exam (MMSE)
Time Frame: Assessed at enrollment, week 7, week 15, week 27, and month 12
Cognitive Ability Metric
Assessed at enrollment, week 7, week 15, week 27, and month 12

Collaborators and Investigators

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

Sponsor

Walter Reed National Military Medical Center

Investigators

  • Principal Investigator: Timothy R Malone, MD, Walter Reed National Military Medical Center

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 (Anticipated)

January 1, 2020

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

June 1, 2025

Study Registration Dates

First Submitted

June 27, 2019

First Submitted That Met QC Criteria

June 27, 2019

First Posted (Actual)

July 2, 2019

Study Record Updates

Last Update Posted (Actual)

July 2, 2019

Last Update Submitted That Met QC Criteria

June 27, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06272019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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