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RESCUE ESES: a Randomized European trial of Steroids versus Clobazam Usage for Encephalopathy with Electrical Status Epilepticus in Sleep
ISRCTN ISRCTN42686094
DOI 10.1186/ISRCTN42686094
ClinicalTrials.gov identifier
EudraCT number 2013-000531-27
Public title RESCUE ESES: a Randomized European trial of Steroids versus Clobazam Usage for Encephalopathy with Electrical Status Epilepticus in Sleep
Scientific title Corticosteroids or clobazam for ESES syndrome: a European, multicenter, randomized, controlled clinical trial
Acronym RESCUE ESES
Serial number at source 43510
Study hypothesis 1. As compared with treatment with clobazam, treatment with steroids leads to a 25% increase in favourable outcome in children with Encephalopathy with Electrical Status Epilepticus in Sleep (ESES) syndrome
2. In children with atypical ESES syndrome, treatment with corticosteroids or clobazam also leads to cognitive improvement, with a superiority of steroids over clobazam
3. Pro-inflammatory cytokines are increased in patients with ESES syndrome and are potential biomarkers for disease activity and therapeutic outcome
4. Pulsed steroid therapy has the comparable efficacy and less side effects compared to continuous corticosteroid therapy in children with ESES syndrome

On 28/02/2014 the anticipated start date was changed from 01/01/2014 to 01/02/2014.
Lay summary Background and study aims
Encephalopathy with Electrical Status Epilepticus in Sleep (ESES) syndrome is a rare epilepsy syndrome of childhood that is characterized by disturbed electrical brain activity (epilepsy) in sleep and problems with cognition (attention, memory, language, etc.) or behavior. ESES resolves spontaneously in puberty, but cognitive problems often remain. Adequate treatment is mandatory to prevent or reverse these cognitive deficits. However, it is unknown which treatment is the best. Treatment with "standard" anti-epileptic drugs is not very effective. Some studies suggest that clobazam and steroid treatment may be the best option. The only way to prove which treatment is best is to let a lottery decide which treatment a child gets (randomization) and then compare the effects of both treatments. The aim of this study is to establish which treatment is best for children with ESES syndrome, by treating 130 children with ESES syndrome with steroids (inflammation inhibitors) or clobazam and evaluating change in cognitive functioning after 6 and 18 months.

Who can participate?
Children aged 2 up to 12 years with a recent diagnosis of ESES syndrome (within the past six months) can participate in our study.

What does the study involve?
Children will be randomly allocated to either receive corticosteroids or clobazam for six months.

What are the possible benefits and risks of participating?
We hope to prove which of the two treatments is best for children with ESES syndrome. Because these two treatments are also given outside of this study, there are no specific benefits or risks associated with participating. Side-effects of corticosteroids can be e.g. fluid retention and increased infection risk, while e.g. drowsiness and coordination problems can occur while using clobazam. In most cases these side-effects can easily be resolved by changing the dosage.

Where is the study run from?
The study is run from the Brain Center Rudolf Magnus, department of Pediatric Neurology, University Medical Center Utrecht in the Netherlands. Participating centers are located in other European Union countries and include Italy (Pavia), France (Paris, Lyon, Strasbourg), United Kingdom (London, Edinburgh, Glasgow), Belgium (Brussels, Leuven), Germany (Kehl, Freiburg, Kiel, Vogtareuth), Denmark (Dianalund), Finland (Helsinki), Romania (Bucharest), Bulgaria (Sofia) and Spain (Madrid).

When is the study starting and how long is it expected to run for?
This study started in February 2014 and will run for four years.

Who is funding the study?
The study is funded by the National Epilepsy Fund of the Netherlands (NEF) and the Wilhelmina research fund.

Who is the main contact?
Dr F.E. Jansen
f.e.jansen@umcutrecht.nl
Ethics approval 1. Medical Ethics Committee Utrecht, the Netherlands, December 2013, ref: 13-275/G-M
2. In the other participating countries – approval pending
Study design Multi-center randomized controlled clinical trial with blinded outcome assessment
Countries of recruitment Belgium, Bulgaria, Denmark, Finland, France, Germany, Italy, Netherlands, Romania, Spain, United Kingdom
Disease/condition/study domain Encephalopathy with electrical status epilepticus in sleep (ESES syndrome)
Participants - inclusion criteria 1. Age 2 to 12 years
2. A diagnosis within six months prior to study inclusion (preferentially as soon as possible) of either typical or atypical ESES syndrome (as defined in study protocol)
3. No previous treatment with anti-epileptic drugs in the context of ESES
4. No previous treatment with either clobazam or corticosteroids
5. No current treatment with carbamazepine, oxcarbazepine, vigabatrin, tiagabine, gabapentin and pregabalin and no treatment with any of these drugs in the previous three months
6. Written informed consent by parents / legal representatives
Participants - exclusion criteria 1. Patients with a spike wave index during wakefulness of > 50%
2. Any condition that, in the investigator’s judgement, contraindicates the use of clobazam or corticosteroids
Anticipated start date 01/02/2014
Anticipated end date 31/12/2017
Status of trial Ongoing
Patient information material Not available in web format, please use the contact details below to request a patient information sheet
Target number of participants 130
Interventions Corticosteroids (either methylprednisolone pulse therapy or continuous oral prednisolone, depending on local preference) or clobazam.
Primary outcome measure(s) 1. Intelligence quotient, or developmental quotient
2. Cognitive sumscore
Improvement is defined as significant when improved by at least 75% of the standard deviation.
Secondary outcome measure(s) Secondary outcomes will be evaluated after 6 and 18 months:
1. Individual absolute test results, and IQ scores
2. Spike wave index during Non-rapid eye movement (non-REM) sleep. Improvement is defined as a decrease to less than
25%
3. Seizure frequency. Improvement is defined as a reduction of 50% or more as compared with baseline
4. Safety and tolerability, as assessed by the occurrence of serious adverse events
5. Differences in pro-inflammatory cytokine levels in patients with ESES who respond to either treatment strategies compared to non responders

Added 28/02/2014:
6. Assessment of global daily functioning assessed with a visual analogue scale (VAS, -5 to 5)
Sources of funding 1. Dutch National Epilepsy Fund (NEF) (Netherlands)
2. Wilhelmina Children's Hospital, Research Fund (WKZ fund) (Netherlands)

Added 28/02/2014:
3. European Clinical Research Infrastructures Network (ECRIN)
Trial website
Publications
Contact name Dr  Floortje E  Jansen
  Address University Medical Center Utrecht / Wilhelmina Children's Hospital
Department of Pediatric Neurology
Lundlaan 6
  City/town Utrecht
  Zip/Postcode 3584 AE Utrecht
  Country Netherlands
  Tel +31 88 75 543 41
  Fax +31 88 75 553 50
  Email F.E.Jansen@umcutrecht.nl
Sponsor University Medical Center Utrecht (Netherlands)
  Address PO Box 85500
  City/town Utrecht
  Zip/Postcode 3508 GA
  Country Netherlands
  Tel +31 88 75 555 55
  Email info@umcutrecht.nl
  Sponsor website: http://www.umcutrecht.nl/
Date applied 15/04/2013
Last edited 06/03/2014
Date ISRCTN assigned 24/05/2013
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