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

Study Objective

Epileptic encephalopathy with ESES (Electrical Status Epilepticus in Sleep) is a rare pediatric epilepsy syndrome. It resolves spontaneously in puberty but cognitive dysfunction remains, especially when untreated. Corticosteroids as well as clobazam are currently used to treat ESES syndrome but it is not known which treatment has the best prognosis. The primary objective of this study is to compare the effects on cognition of treatment with corticosteroids (intravenous methylprednisolone or oral prednisolone depending on hospital routine practice) and clobazam in children with ESES. The patient population will include children between 2 and 12 years of age.

This is a European, academic, multicenter, randomized, controlled clinical trial in 130 children with ESES syndrome, to compare the effects of corticosteroids versus clobazam on cognition.

The sponsor of the study is the University Medical Center Utrecht (UMCU) and the study will take place in about 24 centres across Europe: The Netherlands, Belgium, UK, France, Germany, Denmark, Finland, Italy, Spain and Romania. The coordinating investigator for the Project is Prof. Floor Jansen (Department of Pediatric Neurology, Rudolf Magnus Institute of Neuroscience, UMCU).

Participation conditions

The trial will include 130 patients with typical or atypical ESES syndrome, fulfilling the following in- and exclusion criteria.

Inclusion criteria

• Age 2 up to 12 years (not including children of 12 years old);

• A diagnosis within six months prior to study inclusion (preferably as close to inclusion as possible)  of either:

o Bilateral sleep-induced epileptiform activity with SWI in > 85% of nonREM sleep and developmental delay, arrest, or regression (“typical ESES syndrome”);

o Arrest or regression of development and bilateral sleep-induced epileptiform activity with a SWI in > 50%, or unilateral sleep induced epileptiform activity with SWI in > 85% of nonREM sleep (“atypical ESES syndrome”);

o Regression of development and unilateral epileptiform activity with a SWI of > 50% of nonREM sleep (“atypical ESES syndrome”);

• No previous treatment with either corticosteroids or clobazam

• No current treatment nor in the previous three months with carbamazepine, oxcarbazepine, vigabatrin, tiagabine, gabapentin and pregabalin. These drugs are known to possibly worsen the outcome in children with ESES syndrome and may therefore influence treatment result. Furthermore, these drugs can increase the SWI during sleep and may cause an electrographic pattern fulfilling the criteria for ESES. Inclusion of such cases with possible “treatment induced ESES” is not desirable.

• Written informed consent by parents / legal representatives

Exclusion criteria

• Patients with a SWI during wakefulness of > 50%
• Acute or chronic infectious disease (e.g. TB, HIV)
• Immunodeficiency
• Severe osteopenia/osteoporosis
• Diabetes
• Cushing syndrome
• Severe respiratory insufficiency
• Severe liver failure
• Severe ulcera
• Any other condition that, in the investigator’s judgement, contra-indicates the use of corticosteroids or clobazam. 

Centers managed by the CIEC:

Belgium:

Universitair Ziekenhuis Brussel (UZ Brussel), Brussels
Universitair Ziekenhuis Leuven (UZ Leuven), Leuven
Hôpital Erasme (ULB), Brussels