Cognitive Effects of Treatment of Interictal Discharges

Not Applicable

Completed

Conditions: Epilepsy

Interventions: Drug: levetiracetam
Drug: Lamotrigine

Registration Number: NCT00916149

Lead Sponsor: Massachusetts General Hospital

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 31

Inclusion Criteria

Not provided

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Levetiracetam	levetiracetam	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.
Lamotrigine	Lamotrigine	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.

Primary Outcome Measures

Name	Time	Method
Mean Change in Focal Interictal Discharges (IEDs) Per Hour, Pre to Post Treatment	1 and 11 weeks	This descriptive analysis examined the change in interictal discharge rates pre to post-treatment with levetiracetam in subjects with epilepsy and with no treatment in healthy controls.

Secondary Outcome Measures

Name	Time	Method
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Trial 1 Learning Score	1 and 11 weeks	Change in California Verbal Learning Test (CVLT) Trial 1 learning score (range 0-16; higher score indicates better memory)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Delayed Recall	1 and 11 weeks	Change in Brief Visuospatial Memory Test-Revised (BVMT-R) Delayed Recall score (the score ranges from 0-6, reflecting the number of shapes recalled after a 25 minute delay)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Total Learning	1 and 11 weeks	Change in California Verbal Learning Test (CVLT) Total Learning Score (the total learning score is summed across 5 learning trials, range 0-80). Higher scores indicate better memory. Scores on the CVLT reflect the number of words recalled.
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Short Delay	1 and 11 weeks	Change in California Verbal Learning Test (CVLT) Short Delay Recall Score (the score ranges from 0-16, reflecting the number of words recalled)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Long Delay	1 and 11 weeks	Change in California Verbal Learning Test (CVLT) Long Delay Recall score (the score ranges from 0-16, reflecting the number of words recalled)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Learning	1 and 11 weeks	Change in Brief Visuospatial Memory Test-Revised (BVMT-R) Learning score (the score ranges from 0-6, reflecting the number of shapes recalled on the initial learning trial)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Total Learning	1 and 11 weeks	Change in Brief Visuospatial Memory Test-Revised (BVMT-R) Total Learning score (the score is summed across 3 learning trials, score range 0-18, reflecting the total number of shapes recalled)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: QOLIE	1 and 11 weeks	Change in Quality of Life Inventory in Epilepsy-89 score (QOLIE; score ranges from 0-100; higher scores reflect better quality of life)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Spatial Span	1 and 11 Weeks	Change in Spatial Span score (score ranges from 0-32; higher scores indicate better performance). Scores indicate the number of spatial sequences correctly recalled, forwards and backwards.
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Trails Test	1 and 11 weeks	Change in Trails Test score (The score is the time for completion in seconds. A lower score reflects better performance.)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Grooved Pegboard	1 and 11 weeks	Change in Grooved Pegboard Score (The score is the time for completion. A lower score reflects better performance.)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Symbol	1 and 11 weeks	Change in Digit Symbol Score (The score is the number of items completed. A higher score reflects better performance.)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Accuracy	1 and 11 weeks	Change in Continuous Performance Test Score - Accuracy (CPT; score ranges from 0-100% correct)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Reaction Time (CPT RT)	1 and 11 weeks	Change in Continuous Performance Test Score - Reaction Time, measured in seconds (CPT RT; less time reflects better performance)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Accuracy	1 and 11 weeks	Change in Choice Accuracy Score (indicate if red or blue stimulus; accuracy 0-100%)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Reaction Time	1 and 11 weeks	Change in Choice Reaction Time Score, with reaction time measured in seconds (indicate if red or blue stimulus; lower reaction time suggests better performance)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Accuracy	1 and 11 weeks	Change in Verbal Working Memory Accuracy Score (range 0-100%)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Reaction Time	1 and 11 weeks	Change in Verbal Working Memory Reaction Time Score, with reaction time measured in seconds (indicates processing speed)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Accuracy	1 and 11 weeks	Change in Non-verbal Working Memory Accuracy Score (accuracy ranges from 0-100%)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Reaction Time	1 and 11 weeks	Change in Non-verbal Working Memory Reaction Time Score (indicates processing speed, with reaction time measured in seconds)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Accuracy	1 and 11 weeks	Change in Verbal Recognition Accuracy Score (accuracy ranges from 0-100%)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: LNS	1 and 11 weeks	Change in Letter-Number Sequencing score (LNS; score ranges from 0-21; higher scores indicate better performance). The score reflects the number of items that the subject can correctly recall and place in proper alphabetical and numerical sequence.
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Span	1 and 11 weeks	Change in Digit Span score (score ranges from 0-30; higher scores indicate better performance). Scores indicate the number of digit sequences correctly recalled, forwards and backwards.
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Fluency	1 and 11 weeks	Change in Verbal Fluency score (Score range: lowest score = 0, with no upper limit, reflecting total number of words generated. Higher scores indicate better performance.)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Stroop	1 and 11 weeks	Change in Stroop score (The score is the time for completion in seconds; less time reflects better performance.)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Design Fluency	1 and 11 weeks	Change in Design Fluency score (Score range: lowest score = 0; there is no upper limit. A higher score reflects more designs generated, hence better performance.)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Adverse Events Profile (AEP)	1 and 11 weeks	Change in Adverse Events Profile score (scores range from 19-76; higher scores indicate greater side effects)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Reaction Time	1 and 11 weeks	Change in Verbal Recognition Reaction Time Score (indicates processing speed, with reaction time measured in seconds)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Accuracy	1 and 11 weeks	Change in Facial Recognition Accuracy Score (accuracy ranges from 0-100%)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Reaction Time	1 and 11 weeks	Change in Facial Recognition Reaction Time Score (indicates processing speed, with reaction time measured in seconds)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: NDDIE	1 and 11 weeks	Change in Neurological Disorders Depression Inventory for Epilepsy (NDDIE) score (scores range from 0-24; higher scores indicate greater depressive symptoms)