EpilepsyNCT00916149
Cognitive Effects of Treatment of Interictal Discharges
A study testing levetiracetam and Lamotrigine in people with Epilepsy, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Epilepsy
- What is being tested?
- levetiracetam and Lamotrigine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Oct 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
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.
Read the 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.
- Conditions
- Epilepsy
- Being tested
- levetiracetam, Lamotrigine
- Keywords
- Epilepsy, Cognition, Lamictal, Lamotrigine, Keppra, Levetiracetam
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
levetiracetamDrug
Also called Keppra
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.
LamotrigineDrug
Also called Lamictal
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Lamotrigine |
| No treatment | No intervention | 15 healthy subjects, not receiving anticonvulsant medication, will undergo repeated EEG/cognitive testing as a control. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 and 11 weeks
Secondary outcomes (31)
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Trial 1 Learning Score
Change in California Verbal Learning Test (CVLT) Trial 1 learning score (range 0-16; higher score indicates better memory)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Total Learning
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.
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Short Delay
Change in California Verbal Learning Test (CVLT) Short Delay Recall Score (the score ranges from 0-16, reflecting the number of words recalled)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Long Delay
Change in California Verbal Learning Test (CVLT) Long Delay Recall score (the score ranges from 0-16, reflecting the number of words recalled)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Learning
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)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Total Learning
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)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Delayed Recall
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)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: QOLIE
Change in Quality of Life Inventory in Epilepsy-89 score (QOLIE; score ranges from 0-100; higher scores reflect better quality of life)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: LNS
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.
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Spatial Span
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.
Measured: 1 and 11 Weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Span
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.
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Fluency
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.)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Stroop
Change in Stroop score (The score is the time for completion in seconds; less time reflects better performance.)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Design Fluency
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.)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Trails Test
Change in Trails Test score (The score is the time for completion in seconds. A lower score reflects better performance.)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Grooved Pegboard
Change in Grooved Pegboard Score (The score is the time for completion. A lower score reflects better performance.)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Symbol
Change in Digit Symbol Score (The score is the number of items completed. A higher score reflects better performance.)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Accuracy
Change in Continuous Performance Test Score - Accuracy (CPT; score ranges from 0-100% correct)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Reaction Time (CPT RT)
Change in Continuous Performance Test Score - Reaction Time, measured in seconds (CPT RT; less time reflects better performance)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Accuracy
Change in Choice Accuracy Score (indicate if red or blue stimulus; accuracy 0-100%)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Reaction Time
Change in Choice Reaction Time Score, with reaction time measured in seconds (indicate if red or blue stimulus; lower reaction time suggests better performance)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Accuracy
Change in Verbal Working Memory Accuracy Score (range 0-100%)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Reaction Time
Change in Verbal Working Memory Reaction Time Score, with reaction time measured in seconds (indicates processing speed)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Accuracy
Change in Non-verbal Working Memory Accuracy Score (accuracy ranges from 0-100%)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Reaction Time
Change in Non-verbal Working Memory Reaction Time Score (indicates processing speed, with reaction time measured in seconds)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Accuracy
Change in Verbal Recognition Accuracy Score (accuracy ranges from 0-100%)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Reaction Time
Change in Verbal Recognition Reaction Time Score (indicates processing speed, with reaction time measured in seconds)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Accuracy
Change in Facial Recognition Accuracy Score (accuracy ranges from 0-100%)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Reaction Time
Change in Facial Recognition Reaction Time Score (indicates processing speed, with reaction time measured in seconds)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: NDDIE
Change in Neurological Disorders Depression Inventory for Epilepsy (NDDIE) score (scores range from 0-24; higher scores indicate greater depressive symptoms)
Measured: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Adverse Events Profile (AEP)
Change in Adverse Events Profile score (scores range from 19-76; higher scores indicate greater side effects)
Measured: 1 and 11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2009 (estimated)
- Study startJan 2007
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- UCB Young Investigator Research Program, National EpiFellows Foundation, UCB Pharma, GlaxoSmithKline
- Responsible party
- Principal investigator, Beth Ami Leeman, MD, Massachusetts General Hospital
- Investigators
- Daniel B Hoch, M.D., Ph.D., Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00916149
- Sponsor's protocol ID
- LMC111754
- Status last verified
- Sep 2018
- First submitted
- 5 Jun 2009
- Last updated
- 3 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Aarts JH, Binnie CD, Smit AM, Wilkins AJ. Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain. 1984 Mar;107 ( Pt 1):293-308. doi: 10.1093/brain/107.1.293.
PubMed 6421454Browne 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.
PubMed 4858089Dodrill CB, Wilkus RJ. Relationships between intelligence and electroencephalographic epileptiform activity in adult epileptics. Neurology. 1976 Jun;26(6 PT 1):525-31. doi: 10.1212/wnl.26.6.525.
PubMed 819859Gallagher 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.
PubMed 14692914Goode 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.
PubMed 5276416Hermann 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.
PubMed 8822692HOVEY HB, KOOI KA. Transient disturbances of thought processes and epilepsy. AMA Arch Neurol Psychiatry. 1955 Sep;74(3):287-91. doi: 10.1001/archneurpsyc.1955.02330150053007. No abstract available.
PubMed 13248285Kasteleijn-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.
PubMed 2439294KOOI KA, HOVEY HB. Alterations in mental function and paroxysmal cerebral activity. AMA Arch Neurol Psychiatry. 1957 Sep;78(3):264-71. No abstract available.
PubMed 13457501Lee S, Sziklas V, Andermann F, Farnham S, Risse G, Gustafson M, Gates J, Penovich P, Al-Asmi A, Dubeau F, Jones-Gotman M. The effects of adjunctive topiramate on cognitive function in patients with epilepsy. Epilepsia. 2003 Mar;44(3):339-47. doi: 10.1046/j.1528-1157.2003.27402.x.
PubMed 12614389Lutz MT, Helmstaedter C. EpiTrack: tracking cognitive side effects of medication on attention and executive functions in patients with epilepsy. Epilepsy Behav. 2005 Dec;7(4):708-14. doi: 10.1016/j.yebeh.2005.08.015. Epub 2005 Nov 2.
PubMed 16266826Meador 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.
PubMed 15985582The 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.
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive Effects of Treatment of Interictal Discharges
- ClinicalTrials.gov ID
- NCT00916149
- Acronym / sponsor ID
- LMC111754
- Conditions
- Epilepsy
- Keywords
- Epilepsy, Cognition, Lamictal, Lamotrigine, Keppra, Levetiracetam
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- UCB Young Investigator Research Program, National EpiFellows Foundation, UCB Pharma, GlaxoSmithKline
- Study start
- Jan 2007
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 9 Jun 2009 (estimated)
- Results
- Posted 7 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Levetiracetam | Active comparator | Drug: levetiracetam12 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 | Active comparator | Drug: Lamotrigine12 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. |
| No treatment | No intervention | –15 healthy subjects, not receiving anticonvulsant medication, will undergo repeated EEG/cognitive testing as a control. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| levetiracetamAlso: KeppraThe 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. | Drug | Levetiracetam |
| LamotrigineAlso: LamictalThe 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. | Drug | Lamotrigine |
Primary outcome
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.
31 secondary outcomes
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Trial 1 Learning Score
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Total Learning
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Short Delay
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CVLT Long Delay
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Learning
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Total Learning
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: BVMT-R Delayed Recall
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: QOLIE
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: LNS
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Spatial Span
Time frame: 1 and 11 Weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Span
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Fluency
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Stroop
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Design Fluency
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Trails Test
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Grooved Pegboard
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Digit Symbol
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Accuracy
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: CPT Reaction Time (CPT RT)
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Accuracy
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Choice Reaction Time
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Accuracy
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Working Memory Reaction Time
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Accuracy
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Non-verbal Working Memory Reaction Time
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Accuracy
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Verbal Recognition Reaction Time
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Accuracy
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Facial Recognition Reaction Time
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: NDDIE
Time frame: 1 and 11 weeks
Performance on Neuropsychological Batteries and Computerized Cognitive Testing: Adverse Events Profile (AEP)
Time frame: 1 and 11 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 6421454Aarts JH, Binnie CD, Smit AM, Wilkins AJ. Selective cognitive impairment during focal and generalized epileptiform EEG activity. Brain. 1984 Mar;107 ( Pt 1):293-308. doi: 10.1093/brain/107.1.293.
- Background: PubMed 4858089Browne 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.
- Background: PubMed 819859Dodrill CB, Wilkus RJ. Relationships between intelligence and electroencephalographic epileptiform activity in adult epileptics. Neurology. 1976 Jun;26(6 PT 1):525-31. doi: 10.1212/wnl.26.6.525.
- Background: PubMed 14692914Gallagher 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.
- Background: PubMed 5276416Goode 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.
- Background: PubMed 8822692Hermann 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.
- Background: PubMed 13248285HOVEY HB, KOOI KA. Transient disturbances of thought processes and epilepsy. AMA Arch Neurol Psychiatry. 1955 Sep;74(3):287-91. doi: 10.1001/archneurpsyc.1955.02330150053007. No abstract available.
- Background: PubMed 2439294Kasteleijn-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.
- Background: PubMed 13457501KOOI KA, HOVEY HB. Alterations in mental function and paroxysmal cerebral activity. AMA Arch Neurol Psychiatry. 1957 Sep;78(3):264-71. No abstract available.
- Background: PubMed 12614389Lee S, Sziklas V, Andermann F, Farnham S, Risse G, Gustafson M, Gates J, Penovich P, Al-Asmi A, Dubeau F, Jones-Gotman M. The effects of adjunctive topiramate on cognitive function in patients with epilepsy. Epilepsia. 2003 Mar;44(3):339-47. doi: 10.1046/j.1528-1157.2003.27402.x.
- Background: PubMed 16266826Lutz MT, Helmstaedter C. EpiTrack: tracking cognitive side effects of medication on attention and executive functions in patients with epilepsy. Epilepsy Behav. 2005 Dec;7(4):708-14. doi: 10.1016/j.yebeh.2005.08.015. Epub 2005 Nov 2.
- Background: PubMed 15985582Meador 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel B Hoch, M.D., Ph.D. principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing levetiracetam and Lamotrigine in people with Epilepsy, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change in Focal Interictal Discharges (IEDs) Per Hour, Pre to Post Treatment (time frame: 1 and 11 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00916149, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2018.