Seizure, Epileptic
Conditions
Brief summary
Genetic epileptic encephalopathies (EEs) are a group of very rare and severe, pharmaco-resistant epilepsy forms characterized by an early onset, e.g. first years of life, and an often severe developmental delay. Genetic defects were found in different ion channels such as potassium or sodium channels explaining well the pathological neuronal hyperexcitability leading to seizures. Further mutations were also found in proteins relevant for cell structure, DNA/RNA processing or the synaptic vesicular metabolism. Specific and individualized therapies have not been established neither in the clinical routine nor in controlled studies. The goal of this monocentric non-blinded non-placebo controlled phase IIb study is the evaluation of the effectivity of anticonvulsive drugs specifically working on the ion channels defective in some subtypes of EEs in order to establish a standard and individualized therapy for these rare diseases based on the specific genetic defect.
Detailed description
During the study, the sodium channel blockers phenytoin and lacosamide and the potassium channel blocker kinidinsulfate will be given under standardized conditions to patients with an early onset and pharmaco-resistant genetic epilepsy with and without mutations in the potassium channels KCNT1 and KCNQ2 and the sodium channel gene SCN2A. The primary endpoint will be a significant seizure reduction under trial medication compared to baseline. Secondary endpoints will be the improvement of electroencephalographic characteristics of the respective EEs.
Interventions
OTHERTherapy regime
Patient will receive Phenytoin, if no success is obtained, Vimpat is given. In case of success after one of the treatments, the endpoint is reached. Success is defined as reduction of seizures to 50% compared to baseline.
Sponsors
University Hospital Tuebingen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Treatment A - if no positive response: Treatment B
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Months
Healthy volunteers
No
Inclusion criteria
* highly active epilepsy (≥ 1 seizure per day) * epilepsy with onset 0-3 months of age * pharmaco-resistant epilepsy (2 or more standard anticonvulsive medications tried before) * recently max. two stable anticonvulsive drugs for minimum 4 days before study start * patients under continuous monitoring control * patients younger than 1 year of age
Exclusion criteria
* high grade cardial rhythm disorders * severe liver, renal and electrolyte blood parameter changes * metabolic or lesional origin of epilepsy (metabolic screening results and cranial MRI available) * parallel participation in other studies (must be finished two month before study start) * missing informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of seizures | one week | Reduction of epileptic seizures within one treatment phase to 50% compared to baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of seizures stratified for genetic background | one week | Reduction of epileptic seizures within one treatment phase to 50% compared to baseline stratified for three gene mutations |
| Reduction of epileptic activities or suppression phases | one week | Reduction of epileptic activities or suppression phases in EEG |
Countries
Germany
Outcome results
None listed