Electrical Status Epilepticus in Sleep Clinical Trial
— ESES-ClobazamOfficial title:
Electrical Status Epilepticus in Sleep: Response of Neuropsychological Deficits and Epileptiform Activity to Clobazam Treatment
Electrical status epilepticus in sleep (ESES) is a pattern of abnormal discharges in the
electroencephalogram (EEG). Children who have this pattern present seizures and
neuropsychological regression. There are no studies that systematically evaluate the
response of abnormal discharges in the EEG, seizures and neuropsychological regression to
different antiepileptic treatments. Therefore, treatment strategies in ESES are not based on
scientific evidence. High-dose benzodiazepines such as diazepam (valium) have been reported
to improve the severe EEG abnormalities of patients with ESES in the short-term. But the
long-term response of seizures and neuropsychological regression has not been systematically
studied. Clobazam is a benzodiazepine derivative with antiepileptic properties. The
pharmacologic properties of clobazam make of this drug a particularly useful option in ESES:
in patients with ESES the alpha-2 subunit of the GABA receptor is preferentially
up-regulated and clobazam may have a higher affinity for this particular subunit, so
investigators expect a higher effect of this drug on ESES patients than with other
benzodiazepines (Loddenkemper et al, in preparation). The aim of our study is to objectively
evaluate the response to clobazam treatment of neuropsychological deficits, seizures and
abnormal discharges in the EEG in patients with ESES. Clobazam treatment is used in routine
clinical practice and investigators will objectively quantify its effect.
Our working hypothesis is that high-dose clobazam treatment may control the abnormal
epileptiform discharges in the EEG in patients with ESES. The reduction in abnormal
epileptiform discharges may lead to an improvement in neuropsychological deficits and
seizures. The predicted improvement in seizures and neuropsychological function would lead
to a better quality of life in these patients.
Status | Completed |
Enrollment | 17 |
Est. completion date | July 2015 |
Est. primary completion date | July 2015 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 2 Years to 21 Years |
Eligibility |
Inclusion Criteria: - A change in treatment regimen is required because of very active epileptiform activity during sleep and neuropsychological regression. This means that only patients with very active epileptiform activity and, therefore, with a need for a change in treatment regimen as clinically indicated will be potentially eligible. Additionally, a prior clinical decision to use clobazam should have been made by the primary epileptologist in order to participate in the study. - Availability for clinical, neuropsychological and EEG follow-up. Exclusion Criteria: - Electro-clinical evolution that does not require a change in medication regimen or changes in medication regimen that do not include clobazam. |
Observational Model: Cohort, Time Perspective: Prospective
Country | Name | City | State |
---|---|---|---|
United States | Children's Hospital Colorado | Aurora | Colorado |
United States | Boston Children's Hospital | Boston | Massachusetts |
Lead Sponsor | Collaborator |
---|---|
Children's Hospital Boston | Lundbeck LLC |
United States,
Chavakula V, Sánchez Fernández I, Peters JM, Popli G, Bosl W, Rakhade S, Rotenberg A, Loddenkemper T. Automated quantification of spikes. Epilepsy Behav. 2013 Feb;26(2):143-52. doi: 10.1016/j.yebeh.2012.11.048. Epub 2013 Jan 3. — View Citation
De Negri M, Baglietto MG, Battaglia FM, Gaggero R, Pessagno A, Recanati L. Treatment of electrical status epilepticus by short diazepam (DZP) cycles after DZP rectal bolus test. Brain Dev. 1995 Sep-Oct;17(5):330-3. — View Citation
De Negri M. Electrical status epilepticus during sleep (ESES). Different clinical syndromes: towards a unifying view? Brain Dev. 1997 Nov;19(7):447-51. Review. — View Citation
Fernández IS, Chapman KE, Peters JM, Kothare SV, Nordli DR Jr, Jensen FE, Berg AT, Loddenkemper T. The tower of Babel: survey on concepts and terminology in electrical status epilepticus in sleep and continuous spikes and waves during sleep in North America. Epilepsia. 2013 Apr;54(4):741-50. doi: 10.1111/epi.12039. Epub 2012 Nov 16. — View Citation
Fernández IS, Peters J, Takeoka M, Rotenberg A, Prabhu S, Gregas M, Riviello JJ Jr, Kothare S, Loddenkemper T. Patients with electrical status epilepticus in sleep share similar clinical features regardless of their focal or generalized sleep potentiation of epileptiform activity. J Child Neurol. 2013 Jan;28(1):83-9. doi: 10.1177/0883073812440507. Epub 2012 Apr 24. — View Citation
Fernández IS, Peters JM, Hadjiloizou S, Prabhu SP, Zarowski M, Stannard KM, Takeoka M, Rotenberg A, Kothare SV, Loddenkemper T. Clinical staging and electroencephalographic evolution of continuous spikes and waves during sleep. Epilepsia. 2012 Jul;53(7):1185-95. doi: 10.1111/j.1528-1167.2012.03507.x. Epub 2012 May 11. — View Citation
Kramer U, Sagi L, Goldberg-Stern H, Zelnik N, Nissenkorn A, Ben-Zeev B. Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES). Epilepsia. 2009 Jun;50(6):1517-24. doi: 10.1111/j.1528-1167.2008.01891.x. Epub 2008 Nov 19. — View Citation
Loddenkemper T, Fernández IS, Peters JM. Continuous spike and waves during sleep and electrical status epilepticus in sleep. J Clin Neurophysiol. 2011 Apr;28(2):154-64. doi: 10.1097/WNP.0b013e31821213eb. Review. — View Citation
Sánchez Fernández I, Hadjiloizou S, Eksioglu Y, Peters JM, Takeoka M, Tas E, Abdelmoumen I, Rotenberg A, Kothare SV, Riviello JJ Jr, Loddenkemper T. Short-term response of sleep-potentiated spiking to high-dose diazepam in electric status epilepticus during sleep. Pediatr Neurol. 2012 May;46(5):312-8. doi: 10.1016/j.pediatrneurol.2012.02.017. — View Citation
Sánchez Fernández I, Loddenkemper T, Peters JM, Kothare SV. Electrical status epilepticus in sleep: clinical presentation and pathophysiology. Pediatr Neurol. 2012 Dec;47(6):390-410. doi: 10.1016/j.pediatrneurol.2012.06.016. Review. — View Citation
Tassinari CA, Cantalupo G, Rios-Pohl L, Giustina ED, Rubboli G. Encephalopathy with status epilepticus during slow sleep: "the Penelope syndrome". Epilepsia. 2009 Aug;50 Suppl 7:4-8. doi: 10.1111/j.1528-1167.2009.02209.x. — View Citation
Tassinari CA, Rubboli G, Volpi L, Meletti S, d'Orsi G, Franca M, Sabetta AR, Riguzzi P, Gardella E, Zaniboni A, Michelucci R. Encephalopathy with electrical status epilepticus during slow sleep or ESES syndrome including the acquired aphasia. Clin Neurophysiol. 2000 Sep;111 Suppl 2:S94-S102. Review. — View Citation
* Note: There are 12 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Change in seizure frequency | We will review the patient's medical chart to calculate an average seizure frequency before they start clobazam. We will also determine their seizure frequency after being on clobazam for three months in order to calculate the change in seizure frequency in response to starting clobazam. | Measured before and 3 months after starting clobazam | No |
Other | Side effects | We will review any potential side effects with the patient when they return for three month follow-up. We will use the measures in the Common Terminology Criteria for Adverse Events (CTCAE) which are mild, moderate, severe, life threatening and death. | 3 months after starting clobazam | Yes |
Primary | Cognitive ability | A neuropsycholgist will assess the patient's change in cognitive ability in response to treatment with clobazam using theDifferential Ability Scales- Second Edition. | Measured the day before and 3 months after starting treatment | No |
Primary | Language | A neuropsychologist will assess the patient's change in language ability in response to clobazam using the Peabody Picture Vocabulary Test-Fourth Edition, Word Generation and NEPSY: A Developmental Neuropsychological Assessment-Second Edition. | Measured the day before and 3 months after starting treatment. | No |
Primary | Executive function | A parent will fill out the Behavior Rating Inventory of Executive Function, and CogState, to assess the patient's change in executive function in response to clobazam. | Measured the day before and 3 months after starting clobazam | No |
Primary | Adaptive/development skills | A parent will fill out the Scales of Independent Behaviors-Revised and The Developmental Profile-Third Edition to assess the patient's adaptive/developmental skills. | Measured the day before and three months after starting clobazam | No |
Primary | Behavior | The parent will fill out the Child Behavior Checklist to assess the patient's behavior change in response to clobazam. | Measured the day before and three months after starting clobazam | No |
Secondary | Interictal epileptiform activity | We will assess the epileptiform activity in the long-term monitoring unit during three different points for every patient: immediately before the treatment, immediately after the treatment and three months after the treatment. We will assess epileptiform activity using the first five minutes of NREM2 sleep during the first non-REM sleep cycle in each night sleep. We will quantify epileptiform activity using two different methods: 1) the spike-wave percentage as the percentage of one-second bins with at least one spike-wave complex; and 2) the spike frequency as the average number of spike-wave complexes per 100 seconds. | The night before the patient starts Clobazam, the night they start clobazam and three months later | No |