Condition category
Nervous System Diseases
Date applied
15/04/2013
Date assigned
24/05/2013
Last edited
06/03/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English 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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Floortje E Jansen

ORCID ID

Contact details

University Medical Center Utrecht / Wilhelmina Children's Hospital
Department of Pediatric Neurology
Lundlaan 6
Utrecht
3584 AE Utrecht
Netherlands
+31 88 75 543 41
F.E.Jansen@umcutrecht.nl

Additional identifiers

EudraCT number

2013-000531-27

ClinicalTrials.gov number

Protocol/serial number

43510

Study information

Scientific title

Corticosteroids or clobazam for ESES syndrome: a European, multicenter, randomized, controlled clinical trial

Acronym

RESCUE ESES

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.

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

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Encephalopathy with electrical status epilepticus in sleep (ESES syndrome)

Intervention

Corticosteroids (either methylprednisolone pulse therapy or continuous oral prednisolone, depending on local preference) or clobazam.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

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 measures

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)

Overall trial start date

01/02/2014

Overall trial end date

31/12/2017

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

130

Participant 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

Recruitment start date

01/02/2014

Recruitment end date

31/12/2017

Locations

Countries of recruitment

Belgium, Bulgaria, Denmark, Finland, France, Germany, Italy, Netherlands, Romania, Spain, United Kingdom

Trial participating centre

University Medical Center Utrecht / Wilhelmina Children's Hospital
Utrecht
3584 AE Utrecht
Netherlands

Sponsor information

Organisation

University Medical Center Utrecht (Netherlands)

Sponsor details

PO Box 85500
Utrecht
3508 GA
Netherlands
+31 88 75 555 55
info@umcutrecht.nl

Sponsor type

Hospital/treatment centre

Website

http://www.umcutrecht.nl/

Funders

Funder type

Charity

Funder name

Dutch National Epilepsy Fund (NEF) (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Wilhelmina Children's Hospital, Research Fund (WKZ fund) (Netherlands)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Added 28/02/2014:

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

European Clinical Research Infrastructures Network (ECRIN)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes