Levetiracetam for Alzheimer's Disease-Associated Epileptiform Activity
Active, not recruiting
This study will test the use of levetiracetam (Keppra), an approved treatment for epilepsy, to control seizures in people with Alzheimer's disease. Many people with Alzheimer's have seizures and other overactive electrical activity in the brain that is not noticeable but may contribute to the loss of cognitive function.
|Minimum Age||Maximum Age||Gender||Healthy Volunteers|
|45 Years||80 Years||Both||No|
- Probable Alzheimer's disease dementia according to National Institute on Aging-Alzheimer's Association Workgroups criteria, with symptom onset under age 70
- Mini-Mental State Examination (MMSE) score of 18 at initial screening and/or Clinical Dementia Rating (CDR) <2 within 180 days of enrollment
- Presence of epileptiform activity on initial screening with M/EEG
- Caregiver who has daily contact with participant and is willing to attend study visits
- Any concurrent FDA-approved treatment for Alzheimer's, such as donepezil, galantamine, rivastigmine, or memantine, are allowed if on stable dose for at least 2 months prior to enrollment
- Any condition that could account for cognitive deficits in addition to Alzheimer's, including but not limited to vitamin B12 or folate deficiency, abnormal thyroid function, post-traumatic conditions, syphilis, multiple sclerosis or another neuroinflammatory disorder, Parkinson's disease, vascular dementia, Huntington's disease, normal pressure hydrocephalus, central nervous system tumor, progressive supranuclear palsy, or subdural hematoma
- Seizure disorder, except for cases where the first seizure was within 10 years of the Alzheimer's diagnosis and the individual is not prescribed anticonvulsants
- Significant systemic medical illnesses
- Use of medications likely to affect central nervous system functions (such as benzodiazepines and narcotics)
- Severe renal dysfunction with creatine clearance <30 ml/min.
- Participation in another Alzheimer's clinical trial within 3 months of screening; treatment with another investigational drug within 30 days of screening
- Pregnant or lactating
Studies in animals suggest that levetiracetam may reduce neuronal overexcitation and improve cognition in individuals with Alzheimer's disease. This Phase II study will determine if the drug can be used to treat patients with Alzheimer's-associated epileptic brain activity and loss of mental functions.
Participants will be randomly assigned to one of two groups. One group will take levetiracetam twice a day for 4 weeks, then no drug for 4 weeks, then a placebo for 4 weeks. The other group will take a placebo twice a day for 4 weeks, then no treatment for 4 weeks, then levetiracetam for 4 weeks. Participants' cognitive abilities will be tested at the start of the study and then every 4 weeks. The cognitive tests include a virtual-reality navigation test of memory and computerized tests of mental flexibility and problem solving.
Participants will also be monitored with a magnetoencephalogram (MEG) with simultaneous EEG (M/EEG) at their initial visit and after each treatment phase. M/EEG is a highly effective, noninvasive method for identifying brain regions of epileptic activity.
The 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 people.
University of Minnesota
University of California, San Francisco
|Keith A. Vossel, MD||Principal Investigator||University of California, San Francisco|
|Alice L. Lafirstname.lastname@example.org|
Phase 2a Levetiracetam Trial for AD-Associated Network Hyperexcitability
- Verret L, Mann EO, Hang GB, Barth AM, Cobos I, Ho K, Devidze N, Masliah E, Kreitzer AC, Mody I, Mucke L, Palop JJ. Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell. 2012 Apr 27;149(3):708-21. doi: 10.1016/j.cell.2012.02.046.
- 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.
- Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, Gerstein H, Yu GQ, Mucke L. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science. 2007 May 4;316(5825