Pathophysiology Based Therapy of Early Onset Epileptic Encephalopathies (EE)

Pathophysiologie Basierte Therapie Von früh Beginnenden Epileptischen Enzephalopathien

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.

Study Overview

• Status: Withdrawn
• Conditions: Seizure, Epileptic
• Intervention / Treatment: Other: Therapy regime

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • Universtiy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Therapy regime; Two medical drugs will be administered in a predefined order (1. Phenhydan® (Phenytoin), 2. Lacosamide (Vimpat®) to investigate whether this enables an effective reduction of seizures in early onset epileptic encephalopathies..	Other: Therapy 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.; Other Names: two medical products given in a predefined order

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of seizures	Reduction of epileptic seizures within one treatment phase to 50% compared to baseline	one week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of seizures stratified for genetic background	Reduction of epileptic seizures within one treatment phase to 50% compared to baseline stratified for three gene mutations	one week
Reduction of epileptic activities or suppression phases	Reduction of epileptic activities or suppression phases in EEG	one week

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Markus Wolff, Dr., University Children's Hospital Tübingen

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): May 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: November 16, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 21, 2016

Study Record Updates

• Last Update Posted (Actual): February 7, 2020
• Last Update Submitted That Met QC Criteria: February 5, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures
• Other Study ID Numbers: AKF 357-0-0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Study Data/Documents

1. Synopsis

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No