Clinical trial NCT00916149
Conditions: Epilepsy
Keywords: Epilepsy Cognition Lamictal Lamotrigine Keppra Levetiracetam
Sponsor: Massachusetts General Hospital
Start date: 2007-01-01; Completion date: 2012-10-01
Enrollment: 31 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 12 individuals with epilepsy, 6 of whom experience infrequent focal epileptiform discharges and 6 of whom experience frequent focal discharges. These individuals will be treated with levetiracetam (LEV). They will complete repeated EEG/cognitive testing pre- and post-treatment to assess the effects of LEV on discharge frequency, discharge duration, and cognitive task performance. arm 2: 12 individuals with epilepsy, 6 of whom experience infrequent generalized discharges and 6 of whom experience frequent generalized discharges. These individuals will be treated with lamotrigine (LMT). They will complete repeated EEG/cognitive testing pre- and post-treatment to assess the effects of LMT on discharge frequency, discharge duration, and cognitive task performance. arm 3: 15 healthy subjects, not receiving anticonvulsant medication, will undergo repeated EEG/cognitive testing as a control.
Interventions: intervention 1: levetiracetam intervention 2: Lamotrigine
Intervention descriptions: intervention 1: The dosage of levetiracetam will begin at 500mg twice per day (bid) for the first 4 days, and increase by 500mg every 5 days thereafter until a goal of 1500mg bid is reached. The subject will then remain on levetiracetam at 1500mg bid for 8 weeks, until the conclusion of the study. Medication will be supplied in 500mg tablets, to be taken orally. intervention 2: The drug will be supplied in 25, 100 and 150mg tablets, to be taken orally per the titration schedule below:

The regimen will begin at 25mg once per day for the first two weeks, and increase to 50mg once per day during weeks 3 and 4. In week 5, the subject will take 50mg twice per day (bid). The dosage will increase to 50mg in the morning and 100mg at night during week 6. During week 7 the subject will take 100mg bid. During week 8, the subject will take 100mg in the morning and 150mg at night. At week 9, the subject will reach the target dose of 150mg bid. The subject will then remain on lamotrigine at 150mg bid for 7 weeks, until the conclusion of the study.

Protocol documents: