Cognitive Effects of Treatment of Interictal Discharges

NCT00916149 | Completed Results DMC

• 1 other identifier: LMC111754
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Epilepsy

Keywords

Epilepsy; Cognition; Lamictal; Lamotrigine; Keppra; Levetiracetam

Outcome Measures

Primary Outcomes (1)

• Mean Change in Focal Interictal Discharges (IEDs) Per Hour, Pre to Post Treatment

  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.

  1 and 11 weeks

Secondary Outcomes (31)

• Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Trial 1 Learning Score

  1 and 11 weeks

• Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Total Learning

  1 and 11 weeks

• Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Short Delay

  1 and 11 weeks

• Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Long Delay

  1 and 11 weeks

• Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Learning

  1 and 11 weeks

Study Arms (3)

Levetiracetam

ACTIVE COMPARATOR

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

Lamotrigine

ACTIVE COMPARATOR

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

No treatment

NO INTERVENTION

15 healthy subjects, not receiving anticonvulsant medication, will undergo repeated EEG/cognitive testing as a control.

Interventions

levetiracetam DRUG

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.

Also known as: Keppra

Levetiracetam

Lamotrigine DRUG

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.

Also known as: Lamictal

Lamotrigine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• UCB Young Investigator Research Program: collaborator
• National EpiFellows Foundation: collaborator
• UCB Pharma: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (23)

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  PMID: 6421454 BACKGROUND

• Browne TR, Penry JK, Proter RJ, Dreifuss FE. Responsiveness before, during, and after spike-wave paroxysms. Neurology. 1974 Jul;24(7):659-65. doi: 10.1212/wnl.24.7.659. No abstract available.

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• Gallagher MJ, Eisenman LN, Brown KM, Erbayat-Altay E, Hecimovic H, Fessler AJ, Attarian HP, Gilliam FG. Levetiracetam reduces spike-wave density and duration during continuous EEG monitoring in patients with idiopathic generalized epilepsy. Epilepsia. 2004 Jan;45(1):90-1. doi: 10.1111/j.0013-9580.2004.39503.x. No abstract available.

  PMID: 14692914 BACKGROUND

• Goode DJ, Penry JK, Dreifuss FE. Effects of paroxysmal spike-wave on continuous visual-motor performance. Epilepsia. 1970 Sep;11(3):241-54. doi: 10.1111/j.1528-1157.1970.tb03888.x. No abstract available.

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• Hermann BP, Seidenberg M, Schoenfeld J, Peterson J, Leveroni C, Wyler AR. Empirical techniques for determining the reliability, magnitude, and pattern of neuropsychological change after epilepsy surgery. Epilepsia. 1996 Oct;37(10):942-50. doi: 10.1111/j.1528-1157.1996.tb00531.x.

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• Kasteleijn-Nolst Trenite DG, Riemersma JB, Binnie CD, Smit AM, Meinardi H. The influence of subclinical epileptiform EEG discharges on driving behaviour. Electroencephalogr Clin Neurophysiol. 1987 Aug;67(2):167-70. doi: 10.1016/0013-4694(87)90040-x.

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  PMID: 16266826 BACKGROUND

• Meador KJ, Loring DW, Vahle VJ, Ray PG, Werz MA, Fessler AJ, Ogrocki P, Schoenberg MR, Miller JM, Kustra RP. Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology. 2005 Jun 28;64(12):2108-14. doi: 10.1212/01.WNL.0000165994.46777.BE.

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• The Psychological Corporation. Wechsler Test of Adult Reading. 2001, San Antonio, TX: Harcourt Assessment

  BACKGROUND

• Schwab RS. Research Publications. Reaction time in petit mal epilepsy. Association for Research in Nervous and Mental Disease 1947; 26:339-341.

  BACKGROUND

• Selldén U. Psychotechnical performance related to paroxysmal discharges in EEG. Clinical Electroencephalography 1971; 2:18-27.

  BACKGROUND

• Shewmon DA, Erwin RJ. The effect of focal interictal spikes on perception and reaction time. I. General considerations. Electroencephalogr Clin Neurophysiol. 1988 Apr;69(4):319-37. doi: 10.1016/0013-4694(88)90004-1.

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• Shewmon DA, Erwin RJ. The effect of focal interictal spikes on perception and reaction time. II. Neuroanatomic specificity. Electroencephalogr Clin Neurophysiol. 1988 Apr;69(4):338-52. doi: 10.1016/0013-4694(88)90005-3.

  PMID: 2450732 BACKGROUND

• Synder, P.J. Epilepsy. In Snyder, P.J. & Nussbaum, P.D, Clinical neuropsychology: a pocket handbook for assessment. 1998, Washington DC: American Psychological Association.

  BACKGROUND

• Stodieck S, Steinhoff BJ, Kolmsee S, van Rijckevorsel K. Effect of levetiracetam in patients with epilepsy and interictal epileptiform discharges. Seizure. 2001 Dec;10(8):583-7. doi: 10.1053/seiz.2001.0582.

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• Stroup E, Langfitt J, Berg M, McDermott M, Pilcher W, Como P. Predicting verbal memory decline following anterior temporal lobectomy (ATL). Neurology. 2003 Apr 22;60(8):1266-73. doi: 10.1212/01.wnl.0000058765.33878.0d.

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• TIZARD B, MARGERISON JH. THE RELATIONSHIP BETWEEN GENERALIZED PAROXYSMAL E.E.G. DISCHARGES AND VARIOUS TEST SITUATIONS IN TWO EPILEPTIC PATIENTS. J Neurol Neurosurg Psychiatry. 1963 Aug;26(4):308-13. doi: 10.1136/jnnp.26.4.308. No abstract available.

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• Tizard B, Margerison JH. Psychological functions during wave-spike discharge. British Journal of Social and Clinical Psychology 1963b; 3:6-15.

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• Tromp SC, Weber JW, Aldenkamp AP, Arends J, vander Linden I, Diepman L. Relative influence of epileptic seizures and of epilepsy syndrome on cognitive function. J Child Neurol. 2003 Jun;18(6):407-12. doi: 10.1177/08830738030180060501.

  PMID: 12886976 BACKGROUND

MeSH Terms

Conditions

Epilepsy

Interventions

Levetiracetam; Lamotrigine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazines

Results Point of Contact

• Title: Beth Leeman-Markowski, MD
• Organization: VA New York Harbor Healthcare System, NYU

beth.leeman-markowski@nyumc.org

212-686-7500

Study Officials

• Daniel B Hoch, M.D., Ph.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 5, 2009
• First Posted: June 9, 2009
• Study Start: January 1, 2007
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: October 3, 2018
• Results First Posted: August 7, 2018

Record last verified: 2018-09

Locations

US (1)