Clinical trial NCT00916149: Cognitive Effects of Treatment of Interictal Discharges
Official title: Cognitive Effects of Treatment of Interictal Discharges
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Epilepsy
Keywords: Epilepsy
Cognition
Lamictal
Lamotrigine
Keppra
Levetiracetam
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: UCB Young Investigator Research Program
name: National EpiFellows Foundation
name: UCB Pharma
name: GlaxoSmithKline
First posted: 2009-06-09
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if levetiracetam (for patients with focal seizures) or lamotrigine (for patients with generalized seizures) reduces the occurrence of interictal discharges. The study investigates the possible correlation between reduction of interictal discharges and improved cognitive performance.

Detailed description: Subjects with seizures will be studied with electroencephalography (EEG) and offered medication for prevention of recurrent seizures. Those with focal seizures will be treated with levetiracetam, and those with generalized seizures will be treated with lamotrigine. Subjects will undergo repeated EEG with concurrent cognitive testing before and after initiation of treatment. The proposed study tests 3 hypotheses: 1. that treatment with levetiracetam will reduce focal interictal epileptiform activity, 2. that treatment with lamotrigine will reduce generalized interictal epileptiform activity, and 3. that the extent of interictal epileptiform activity is inversely associated with performance on neuropsychological batteries and computerized cognitive testing. Repeated cognitive/neuropsychological testing obtained at steady state of the study drug and again after approximately 2 months on the final dosage will serve to evaluate the timecourse of potential cognitive benefits.

Eligibility criteria: Inclusion Criteria

* 18-55 years of age
* Normal Intelligence Quotient (IQ ≥ 80) as estimated by the Wechsler Test of Adult Reading (WTAR)
* Able to give consent
* The subject's treating physician is planning to prescribe levetiracetam for focal or lamotrigine for generalized seizure prevention
* Either symptomatic or idiopathic seizures.

Exclusion Criteria:

* Non-native English speaking and/or multilingual
* Frequent seizures, since seizures themselves impair cognitive function and present a confounding variable. Subjects may have no more than one seizure or one cluster of seizures per month, with a cluster of seizures including more than one seizure, but between which the patient returns to baseline. The cluster may occur over no more than two consecutive days in one month.
* Seizure(s) must not have occurred within 3 days of enrollment and testing.
* Those with focal seizures who have evidence of renal disease (creatinine clearance less than 80) will be excluded from participation, as levetiracetam is cleared by the kidney.
* Those with focal seizures who have neutrophil counts \<1000/microliter will be excluded from participation, as levetiracetam may lower white blood cell counts.
* Those with focal seizures and irritability or mood swings will not be eligible for participation, as levetiracetam may exacerbate these symptoms. This will be determined by self-report, information obtained from the referring physician and medical record.
* Those with generalized seizures who have moderate to severe liver dysfunction (Child-Pugh Grades B and C) will be excluded from participation, as lamotrigine is cleared by the liver and the proposed dosing may not be tolerable in this population. This will be determined by self-report, information obtained from the referring physician, a comprehensive metabolic panel (routinely obtained in new-onset seizures) and the medical record.
* Subjects who are pregnant will not be eligible to take part in the study, as levetiracetam and lamotrigine are classified as Pregnancy Category C drugs and may pose risk to the fetus. Women of childbearing potential will have a urine pregnancy test prior to participation in the study. The urine pregnancy test will be repeated at the final study visit. Subjects with epilepsy who are of childbearing potential must use acceptable methods of birth control during the study, to be continued until one month after discontinuation of the study drug. If a subject does become pregnant during this time period, she must notify the investigators.
* Women who are breastfeeding may not participate in this study. Levetiracetam and lamotrigine may pass into the breastmilk of nursing mothers, posing a risk to the baby.
* Hypersensitivity to lamotrigine, levetiracetam or any components of these products

Primary outcomes:
measure: Mean Change in Focal Interictal Discharges (IEDs) Per Hour, Pre to Post Treatment
timeFrame: 1 and 11 weeks
Secondary outcomes:
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Trial 1 Learning Score
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Total Learning
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Short Delay
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Long Delay
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Learning
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Total Learning
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Delayed Recall
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: QOLIE
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: LNS
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Spatial Span
timeFrame: 1 and 11 Weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Span
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Fluency
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Stroop
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Design Fluency
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Trails Test
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Grooved Pegboard
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Symbol
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Accuracy
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Reaction Time (CPT RT)
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Accuracy
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Reaction Time
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Accuracy
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Reaction Time
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Accuracy
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Reaction Time
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Accuracy
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Reaction Time
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Accuracy
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Reaction Time
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: NDDIE
timeFrame: 1 and 11 weeks
measure: Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Adverse Events Profile (AEP)
timeFrame: 1 and 11 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Daniel B Hoch, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
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