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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
  Purpose

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.


Condition Intervention
Epilepsy
Drug: levetiracetam
Drug: Lamotrigine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cognitive Effects of Treatment of Interictal Discharges

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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 ]

Estimated Enrollment: 39
Study Start Date: January 2007
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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
No Intervention: No treatment
15 healthy subjects, not receiving anticonvulsant medication, will undergo repeated EEG/cognitive testing as a control.

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00916149

Contacts
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

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Daniel B Hoch, M.D., Ph.D.         
Sponsors and Collaborators
Massachusetts General Hospital
UCB Young Investigator Research Program
National EpiFellows Foundation
UCB Pharma
GlaxoSmithKline
Investigators
Principal Investigator: Daniel B Hoch, M.D., Ph.D. Massachusetts General Hospital
  More Information

Additional Information:
Publications:
Lee, S., Sziklas, V., Andermann, F., Farnham, S., Risse, G., Gustafson, M., Gates, J., Penovich, P., Al-Asmi, A., Dubeau, F., and Jones-Gotman, M. The effects of topiramate on cognitive functioning in patients with epilepsy. Epilepsia 2003; 44:339-347.
Schwab RS. Research Publications. Reaction time in petit mal epilepsy. Association for Research in Nervous and Mental Disease 1947; 26:339-341.
Selldén U. Psychotechnical performance related to paroxysmal discharges in EEG. Clinical Electroencephalography 1971; 2:18-27.
Synder, P.J. Epilepsy. In Snyder, P.J. & Nussbaum, P.D, Clinical neuropsychology: a pocket handbook for assessment. 1998, Washington DC: American Psychological Association.
Tizard B, Margerison JH. Psychological functions during wave-spike discharge. British Journal of Social and Clinical Psychology 1963b; 3:6-15.

Responsible Party: Beth Ami Leeman, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00916149     History of Changes
Other Study ID Numbers: LMC111754
Study First Received: June 5, 2009
Last Updated: January 4, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Epilepsy
Cognition
Lamictal
Lamotrigine
Keppra
Levetiracetam

Additional relevant MeSH terms:
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Anticonvulsants
Etiracetam
Lamotrigine
Piracetam
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Nootropic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sodium Channel Blockers
Therapeutic Uses
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on November 19, 2014