NCT02127918

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Jul 2012

Typical duration for all trials

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2012

Completed
1.6 years until next milestone

First Submitted

Initial submission to the registry

January 27, 2014

Completed
3 months until next milestone

First Posted

Study publicly available on registry

May 1, 2014

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2015

Completed
Last Updated

July 30, 2015

Status Verified

July 1, 2015

Enrollment Period

3 years

First QC Date

January 27, 2014

Last Update Submit

July 28, 2015

Conditions

Electrical Status Epilepticus in Sleep

Keywords

Electrical status epilepticus in sleepContinuous spikes and waves during sleepChildrenElectroencephalogramNeuropsychologyDevelopmentAntiepileptic drugsClobazamSeizures

Outcome Measures

Primary Outcomes (5)

  • 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

  • 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.

  • 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

  • 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

  • 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

Secondary Outcomes (1)

  • Interictal epileptiform activity

    The night before the patient starts Clobazam, the night they start clobazam and three months later

Other Outcomes (2)

  • Change in seizure frequency

    Measured before and 3 months after starting clobazam

  • Side effects

    3 months after starting clobazam

Study Arms (1)

ESES treated with clobazam

The patients that will participate in the protocol will be those that are administered for clinical reasons oral clobazam.

Drug: ESES treated with clobazam

Interventions

ESES treated with clobazamDRUG

The patients that will participate in the protocol will be those that are administered for clinical reasons oral clobazam.

ESES treated with clobazam

Eligibility Criteria

Age2 Years - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Investigators will enroll patients with ESES studied at our centers and treated with high-dose clobazam treatment as decided by the clinical epileptologist. Patients with ESES are monitored once or twice a year in the long-term electroencephalogram monitoring unit to assess epileptiform activity. Patients with very active discharges and neuropsychological regression require a change in their treatment regimen. If the treating epileptologist decides that high-dose cloblazam treatment is indicated for clinical reasons, then the patient will be offered to participate in the study. The research team will not be responsible for or influence the treatment decisions in any way.

You may qualify if:

  • 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.

You may not qualify if:

  • Electro-clinical evolution that does not require a change in medication regimen or changes in medication regimen that do not include clobazam.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (12)

  • Fernandez 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.

    PMID: 23163318BACKGROUND

  • Chavakula V, Sanchez Fernandez 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.

    PMID: 23291250BACKGROUND

  • Sanchez Fernandez 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.

    PMID: 23127259BACKGROUND

  • Fernandez 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.

    PMID: 22578248BACKGROUND

  • Fernandez 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.

    PMID: 22532549BACKGROUND

  • Sanchez Fernandez 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.

    PMID: 22520353BACKGROUND

  • Loddenkemper T, Fernandez 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.

    PMID: 21399511BACKGROUND

  • 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.

    PMID: 19682041BACKGROUND

  • 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. doi: 10.1016/s1388-2457(00)00408-9.

    PMID: 10996561BACKGROUND

  • De Negri M. Electrical status epilepticus during sleep (ESES). Different clinical syndromes: towards a unifying view? Brain Dev. 1997 Nov;19(7):447-51.

    PMID: 9408589BACKGROUND

  • 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. doi: 10.1016/0387-7604(95)00076-n.

    PMID: 8579219BACKGROUND

  • 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.

    PMID: 19054417BACKGROUND

MeSH Terms

Conditions

Seizures

Interventions

Clobazam

Condition Hierarchy (Ancestors)

Neurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Tobias Loddenkemper, MD

    Boston Children's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Target Duration
3 Months
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Neurology

Study Record Dates

First Submitted

January 27, 2014

First Posted

May 1, 2014

Study Start

July 1, 2012

Primary Completion

July 1, 2015

Study Completion

July 1, 2015

Last Updated

July 30, 2015

Record last verified: 2015-07

Locations

US(2)