We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cognitive Effects of Treatment of Interictal Discharges

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00916149
Recruitment Status : Completed
First Posted : June 9, 2009
Results First Posted : August 7, 2018
Last Update Posted : October 3, 2018
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

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.

Condition or disease Intervention/treatment Phase
Epilepsy Drug: levetiracetam Drug: Lamotrigine Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cognitive Effects of Treatment of Interictal Discharges
Study Start Date : January 2007
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. Mean Change in Focal Interictal Discharges (IEDs) Per Hour, Pre to Post Treatment [ Time Frame: 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 :
  1. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Trial 1 Learning Score [ Time Frame: 1 and 11 weeks ]
    Change in California Verbal Learning Test (CVLT) Trial 1 learning score (range 0-16; higher score indicates better memory)

  2. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Total Learning [ Time Frame: 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.

  3. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Short Delay [ Time Frame: 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)

  4. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Long Delay [ Time Frame: 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)

  5. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Learning [ Time Frame: 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)

  6. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Total Learning [ Time Frame: 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)

  7. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Delayed Recall [ Time Frame: 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)

  8. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: QOLIE [ Time Frame: 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)

  9. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: LNS [ Time Frame: 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.

  10. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Spatial Span [ Time Frame: 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.

  11. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Span [ Time Frame: 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.

  12. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Fluency [ Time Frame: 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.)

  13. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Stroop [ Time Frame: 1 and 11 weeks ]
    Change in Stroop score (The score is the time for completion in seconds; less time reflects better performance.)

  14. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Design Fluency [ Time Frame: 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.)

  15. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Trails Test [ Time Frame: 1 and 11 weeks ]
    Change in Trails Test score (The score is the time for completion in seconds. A lower score reflects better performance.)

  16. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Grooved Pegboard [ Time Frame: 1 and 11 weeks ]
    Change in Grooved Pegboard Score (The score is the time for completion. A lower score reflects better performance.)

  17. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Symbol [ Time Frame: 1 and 11 weeks ]
    Change in Digit Symbol Score (The score is the number of items completed. A higher score reflects better performance.)

  18. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Accuracy [ Time Frame: 1 and 11 weeks ]
    Change in Continuous Performance Test Score - Accuracy (CPT; score ranges from 0-100% correct)

  19. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Reaction Time (CPT RT) [ Time Frame: 1 and 11 weeks ]
    Change in Continuous Performance Test Score - Reaction Time, measured in seconds (CPT RT; less time reflects better performance)

  20. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Accuracy [ Time Frame: 1 and 11 weeks ]
    Change in Choice Accuracy Score (indicate if red or blue stimulus; accuracy 0-100%)

  21. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Reaction Time [ Time Frame: 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)

  22. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Accuracy [ Time Frame: 1 and 11 weeks ]
    Change in Verbal Working Memory Accuracy Score (range 0-100%)

  23. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Reaction Time [ Time Frame: 1 and 11 weeks ]
    Change in Verbal Working Memory Reaction Time Score, with reaction time measured in seconds (indicates processing speed)

  24. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Accuracy [ Time Frame: 1 and 11 weeks ]
    Change in Non-verbal Working Memory Accuracy Score (accuracy ranges from 0-100%)

  25. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Reaction Time [ Time Frame: 1 and 11 weeks ]
    Change in Non-verbal Working Memory Reaction Time Score (indicates processing speed, with reaction time measured in seconds)

  26. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Accuracy [ Time Frame: 1 and 11 weeks ]
    Change in Verbal Recognition Accuracy Score (accuracy ranges from 0-100%)

  27. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Reaction Time [ Time Frame: 1 and 11 weeks ]
    Change in Verbal Recognition Reaction Time Score (indicates processing speed, with reaction time measured in seconds)

  28. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Accuracy [ Time Frame: 1 and 11 weeks ]
    Change in Facial Recognition Accuracy Score (accuracy ranges from 0-100%)

  29. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Reaction Time [ Time Frame: 1 and 11 weeks ]
    Change in Facial Recognition Reaction Time Score (indicates processing speed, with reaction time measured in seconds)

  30. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: NDDIE [ Time Frame: 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)

  31. Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Adverse Events Profile (AEP) [ Time Frame: 1 and 11 weeks ]
    Change in Adverse Events Profile score (scores range from 19-76; higher scores indicate greater side effects)



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • 18-55 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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00916149


Locations
Layout table for location information
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
UCB Young Investigator Research Program
National EpiFellows Foundation
UCB Pharma
GlaxoSmithKline
Investigators
Layout table for investigator information
Principal Investigator: Daniel B Hoch, M.D., Ph.D. Massachusetts General Hospital
Publications:
The Psychological Corporation. Wechsler Test of Adult Reading. 2001, San Antonio, TX: Harcourt Assessment
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.

Layout table for additonal information
Responsible Party: Beth Ami Leeman, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00916149    
Other Study ID Numbers: LMC111754
First Posted: June 9, 2009    Key Record Dates
Results First Posted: August 7, 2018
Last Update Posted: October 3, 2018
Last Verified: September 2018
Keywords provided by Beth Ami Leeman, MD, Massachusetts General Hospital:
Epilepsy
Cognition
Lamictal
Lamotrigine
Keppra
Levetiracetam
Additional relevant MeSH terms:
Layout table for MeSH terms
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lamotrigine
Levetiracetam
Anticonvulsants
Nootropic Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Sodium Channel Blockers