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Cognitive Effects of Treatment of Interictal Discharges

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Massachusetts General Hospital
Sponsor:
Collaborators:
UCB Young Investigator Research Program
National EpiFellows Foundation
UCB Pharma
GlaxoSmithKline
Information provided by (Responsible Party):
Beth Ami Leeman, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00916149
First received: June 5, 2009
Last updated: January 4, 2013
Last verified: January 2013

June 5, 2009
January 4, 2013
January 2007
December 2013   (final data collection date for primary outcome measure)
  • Reduction of focal interictal discharges. The proposed study tests the hypothesis that treatment with levetiracetam will reduce focal interictal epileptiform activity. [ Time Frame: 1, 4, and 11 weeks ] [ Designated as safety issue: No ]
  • Reduction of generalized interictal discharges. The proposed study tests the hypothesis that treatment with lamotrigine will reduce generalized interictal epileptiform activity. [ Time Frame: 1, 10, and 15 weeks ] [ Designated as safety issue: No ]
  • The study will evaluate the hypothesis that reduction of focal and generalized interictal epileptiform activity is associated with improved performance on neuropsychological batteries and computerized cognitive testing. [ Time Frame: 1, 4, and 11 weeks (Arm 1) or 1, 10, and 15 weeks (Arm 2) ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00916149 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Cognitive Effects of Treatment of Interictal Discharges
Cognitive Effects of Treatment of Interictal Discharges

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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Epilepsy
  • Drug: levetiracetam
    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.
    Other Name: Keppra
  • Drug: Lamotrigine

    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.

    Other Name: Lamictal
  • Active Comparator: 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.
    Intervention: Drug: levetiracetam
  • Active Comparator: 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.
    Intervention: Drug: Lamotrigine
  • No Intervention: No treatment
    15 healthy subjects, not receiving anticonvulsant medication, will undergo repeated EEG/cognitive testing as a control.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
39
December 2013
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria

  • 18-65 years of age
  • Normal 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/uL 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
Both
18 Years to 65 Years
Yes
Contact: Samantha R Donovan, B.S. 617-643-4617 sdonovan@mclean.harvard.edu
Contact: Beth A Leeman, M.D. 404-778-3181 baleeman@partners.org
United States
 
NCT00916149
LMC111754
Yes
Beth Ami Leeman, MD, Massachusetts General Hospital
Massachusetts General Hospital
  • UCB Young Investigator Research Program
  • National EpiFellows Foundation
  • UCB Pharma
  • GlaxoSmithKline
Principal Investigator: Daniel B Hoch, M.D., Ph.D. Massachusetts General Hospital
Massachusetts General Hospital
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP