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Levetiracetam for Alzheimer's Disease-Associated Epileptiform Activity

Information source: University of California, San Francisco
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Early-onset Alzheimer's Disease

Intervention: levetiracetam (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of California, San Francisco

Official(s) and/or principal investigator(s):
Keith A Vossel, MD, MSc, Principal Investigator, Affiliation: University of California, San Francisco

Overall contact:
Alexander J Beagle, BA, Phone: 415-476-2906, Email: abeagle@memory.ucsf.edu

Summary

Patients with Alzheimer's disease (AD) have seizures in addition to losing their memory and other mental functions (referred to as cognitive functions). The seizures, and other examples of overactive electrical activity in the brain that is not noticeable, contribute to the loss of cognitive function. Studies in animal models suggest that a drug that prevents seizures called levetiracetam may reduce neuronal over-excitation and improve cognition in individuals with AD. We propose to determine if levetiracetam can also be used to treat patients with AD-associated seizures and loss of mental functions. We developed novel instruments for this population that will also be used in future large-scale clinical trials. The current study will last for 12 weeks and will involve people with early-onset AD and epileptic brain activity. Participants will be initially examined and then assigned to groups in a randomized manner. One group will receive levetiracetam for 4 weeks, then no drug for 4 weeks, and then placebo for 4 weeks. For another group, the order of treatments will be reversed. The cognitive abilities of participants will be retested every 4 weeks and compared to those at the beginning. The cognitive tests include a virtual-reality navigation test of memory and computerized tests of mental flexibility and problem solving. The participants will be monitored with a magnetoencephalogram (MEG) with simultaneous EEG (M/EEG) at their initial visit and after each treatment phase (levetiracetam and placebo). M/EEG is a highly effective non-invasive method for identifying brain regions of epileptic activity. We will need to recruit 36 randomized participants to test our hypotheses. This study will take place at the University of California, San Francisco (UCSF) Memory and Aging Center, which is a large referral site for early-onset dementias, and the Department of Radiology. Our overall goal is to demonstrate that levetiracetam engages the intended brain target by suppressing epileptic activity and provides cognitive benefit in a select group of patients who would be predicted to respond favorably to this treatment.

Clinical Details

Official title: Phase 2a Levetiracetam Trial for AD-Associated Network Hyperexcitability

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

Primary outcome: Changes in Executive Function as Measured by the E.X.A.M.I.N.E.R. Computer Battery

Secondary outcome:

Changes in Epileptiform Activity Frequency

Changes in Cognitive Function

Changes in Behavior and Level of Disability

Eligibility

Minimum age: 45 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

To be included in the trial all of the following inclusion criteria must be met: Ability to obtain written informed consent from the patient or caregiver as a surrogate; Meets National Institute on Aging-Alzheimer's Association Workgroups criteria for probable AD dementia (McKhann et al. 2011), with symptom onset < age 70; Presence of epileptiform activity on initial screening M/EEG; Willing and able caregiver who has daily contact with the subject; Mini-Mental State Examination (MMSE) score of ≥ 18 at the initial screening assessment, and/or Clinical Dementia Rating (CDR) < 2 within 180 days of enrollment; Subjects and caregivers must be able to comply with prescribed regime of study treatment throughout the course of the study, and meet the required time commitment of four days of in-person visits; Any concurrent FDA-approved treatment for AD (such as donepezil, galantamine, or rivastigmine, and memantine) must be stable for at least 2 months prior to enrollment. Other medications (except those listed under exclusion criteria) are allowed as long as the dose is stable for 30 days prior to enrollment. The following criteria are considered grounds for exclusion: Any conditions which could account for cognitive deficits in addition to AD, including but not limited to Vitamin B12 or folate deficiency, abnormal thyroid function, posttraumatic conditions, syphilis, multiple sclerosis or another neuroinflammatory disorder, Parkinson's disease, vascular or multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, central nervous system (CNS) tumor, progressive supranuclear palsy, subdural hematoma, etc.; Seizure disorders, excepting cases where the first seizure was within 10 years of the AD diagnosis and the patient is not prescribed anticonvulsants; Significant systemic medical illnesses; Use of medications likely to affect CNS functions (e. g., benzodiazepines, narcotics); Severe renal dysfunction with creatine clearance < 30 ml/min, which would affect serum LEV levels; Participation in another AD clinical trial within 3 months of Screening, or any AD clinical trial, such as a vaccine, that has potential long-term effects; Treatment with another study drug or investigational drug within 30 days of Screening; Pregnant or lactating; Any other medical condition which is determined by the investigators to potentially create an undue risk for an adverse effect; Biomarker evidence unsupportive of a diagnosis of AD.

Locations and Contacts

Alexander J Beagle, BA, Phone: 415-476-2906, Email: abeagle@memory.ucsf.edu

UCSF, San Francisco, California 94158, United States; Recruiting
Alexander J Beagle, BA, Phone: 415-476-2906, Email: abeagle@memory.ucsf.edu
Keith A Vossel, MD, MSc, Principal Investigator
Additional Information

Memory & Aging Center Website

Related publications:

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Sanchez PE, Zhu L, Verret L, Vossel KA, Orr AG, Cirrito JR, Devidze N, Ho K, Yu GQ, Palop JJ, Mucke L. Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model. Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):E2895-903. doi: 10.1073/pnas.1121081109. Epub 2012 Aug 6.

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Starting date: June 2014
Last updated: May 26, 2015

Page last updated: August 23, 2015

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