Levetiracetam for Alzheimer's Disease Neuropsychiatric Symptoms Related to Epilepsy Trial (LAPSE) (LAPSE)
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|ClinicalTrials.gov Identifier: NCT04004702|
Recruitment Status : Not yet recruiting
First Posted : July 2, 2019
Last Update Posted : July 2, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Disease||Drug: Levetiracetam||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||65 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Participants with clinical Alzheimer's disease and neuro-psychiatric symptoms will all be assessed with electroencephalogram, and all participants with epileptiform discharges will receive levetiracetam. Those without epileptiform discharges will be followed with serial inventories of symptom severity and functioning, but will not receive experimental treatment nor placebo.|
|Masking:||None (Open Label)|
|Official Title:||Levetiracetam for Alzheimer's Disease Neuropsychiatric Symptoms Related to Epilepsy Trial (LAPSE) - A Phase II Exploratory Study|
|Estimated Study Start Date :||January 2020|
|Estimated Primary Completion Date :||December 2024|
|Estimated Study Completion Date :||June 2025|
All patients with epileptiform activity on initial screening EEG will receive levetiracetam for 1 year
Levetiracetam 500mg twice a day
Other Name: Keppra
- Change in Neuropsychiatric Inventory Score (NPI) [ Time Frame: Assessed at enrollment, week 7, week 15, week 27, and month 12 ]Neuropsychiatric Symptom Metric
- 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
- 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
- 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
- Change in Mini-Mental State Exam (MMSE) [ Time Frame: Assessed at enrollment, week 7, week 15, week 27, and month 12 ]Cognitive Ability Metric
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): NCT04004702
|Contact: Timothy R Malone, MDfirstname.lastname@example.org|
|United States, Maryland|
|Walter Reed National Military Medical Center||Not yet recruiting|
|Bethesda, Maryland, United States, 20889|
|Contact: Timothy R Malone, MD 301-295-4771 email@example.com|
|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|
|Principal Investigator:||Timothy R Malone, MD||Walter Reed National Military Medical Center|