To compare the effect on cognition of treatment with clobazam or corticosteroids.
ID
Source
Brief title
Condition
- Seizures (incl subtypes)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Intelligence quotient, or developmental quotient
- Cognitive sumscore
Improvement is defined as significant when improved by at least 75% of the
standard deviation.
Secondary outcome
- Individual absolute test results, and IQ scores;
- Spike wave index during non-REM sleep. Improvement is defined as a rdecrease
to less than
25%;
- Seizure frequency. Improvement is defined as a reduction of 50% or more as
compared with
baseline;
- Global improvement of functioning assessed with a VAS score (-5 to 5)
- Safety and tolerability, as assessed by the occurrence of serious
adverse events;
- Differences in pro-inflammatory cytokine levels in patients with ESES
who respond to either treatment strategies compared to nonresponders.
Secondary outcomes will be evaluated after 6 and 18 months.
Background summary
Epileptic encephalopathy with ESES is a rare pediatric epilepsy syndrome with
abundant interictal epileptiform discharges in sleep and impairment of
cognition or behavior. ESES resolves spontaneously in puberty but cognitive
dysfunction often remains, especially when untreated. Treatment with
conventional anti-epileptic drugs yields limited effects. Observational data
have suggested that clobazam and corticosteroid treatment may be beneficial.
Evidence from randomized controlled trials (RCT) to prove efficacy of both
treatment options, or superiority of one over the other, is still lacking and
mandatory.
Study objective
To compare the effect on cognition of treatment with clobazam or
corticosteroids.
Study design
This is a European randomized open clinical trial in 130 patients with recent
onset epileptic encephalopathy with ESES, to compare the effects of
corticosteroid versus clobazam on cognition. Clobazam treatment will be
increased to 0.5-1.2 mg/kg/day if tolerated. Corticosteroids will be given
either intravenously (pulsed methylprednisolone 20 mg/kg/day for 3 days, once
monthly) or orally (prednisolone 2 mg/kg/day for one month, followed by
tapering in 20 weeks).
Intervention
Treatment with clobazam or corticosteroids.
Study burden and risks
The treatments and investigations that are given / performed in the setting of
this study are part of standard clinical patient care, with the exception of
cytokine profiling and detection of auto-antibodies. Blood withdrawal for
cytokine profiling and detection of auto-antibodies will be combined with blood
withdrawal for standard patient care as much as possible. Therefore we suggest
that the burden and risks associated with participation in this study are not
increased. Patients may benefit from the well-defined protocolized patient care
that is implemented in this study (while there are no clear guidelines for
standard clinical patient care in ESES patients outside of this study) and the
patient group of ESES patients may benefit from an evidence based treatment
regimen that can result from this study.
Lundlaan 6
Utrecht 3584 AE
NL
Lundlaan 6
Utrecht 3584 AE
NL
Listed location countries
Age
Inclusion criteria
*Age 2 to 12 years
*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)
*No previous treatment with either clobazam or corticosteroids
*No current treatment with carbamazepine, oxcarbazepine, vigabatrin, tiagabine,
gabapentin and pregabalin and no treatment with any of these drugs in the
previous three months;
*Written informed consent by parents / legal representatives.
Exclusion criteria
*Patients with a spike wave index during wakefulness of > 50%
*Any condition that, in the investigator*s judgement, contraindicates the use
of clobazam or corticosteroids.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000531-27-NL |
| ISRCTN | ISRCTN42686094 |
| CCMO | NL43510.041.13 |