Phase 2a Levetiracetam Trial for AD-Associated Network Hyperexcitability
Sponsor:
Brief Summary:
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 of AD suggest that a drug that
prevents seizures called levetiracetam may reduce neuronal over-excitation and improve
cognition. Based on this evidence, the investigators propose to determine if levetiracetam
can be used to treat patients with AD. The investigators 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 AD. Participants will
be initially examined with an overnight brain wave study to assess for silent epileptic
(seizure-like) activity. Presence of epileptic activity on the screening exam is not required
to enter the trial. Participants will then be 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 each visit. M/EEG is a highly
effective non-invasive method for identifying brain regions of epileptic activity. The
investigators will need to recruit 36 randomized participants to test the study hypotheses.
This study will take place at the University of California, San Francisco (UCSF) and the
University of Minnesota.
Criteria
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); Age ≤ 80 years at time of screening; Willing and able
caregiver who has daily contact with the subject; Mini-Mental State Examination (MMSE)
score ≥ 18 and/or Clinical Dementia Rating (CDR) < 2 at the initial screening assessment;
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 treatment for AD approved by the Food and Drug
Administration (FDA), such as donepezil, galantamine, or rivastigmine, and memantine, must
be stable for at least 30 days prior to screening and at least 60 days prior to study day
1. Other medications (except those listed under exclusion criteria) are allowed as long as
the dose is stable for 30 days prior to screening.
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.; Previous history of a seizure disorder, excepting cases where the first
seizure or detection of epileptiform activity was within 5 years of screening and the
patient is not prescribed an anticonvulsant; 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
- UCSF, San Francisco, California, United States, 94158
