<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02968966</url>
  </required_header>
  <id_info>
    <org_study_id>AKF 357-0-0</org_study_id>
    <nct_id>NCT02968966</nct_id>
  </id_info>
  <brief_title>Pathophysiology Based Therapy of Early Onset Epileptic Encephalopathies</brief_title>
  <acronym>EE</acronym>
  <official_title>Pathophysiologie Basierte Therapie Von früh Beginnenden Epileptischen Enzephalopathien</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital Tuebingen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital Tuebingen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Genetic epileptic encephalopathies (EEs) are a group of very rare and severe,&#xD;
      pharmaco-resistant epilepsy forms characterized by an early onset, e.g. first years of life,&#xD;
      and an often severe developmental delay. Genetic defects were found in different ion channels&#xD;
      such as potassium or sodium channels explaining well the pathological neuronal&#xD;
      hyperexcitability leading to seizures. Further mutations were also found in proteins relevant&#xD;
      for cell structure, DNA/RNA processing or the synaptic vesicular metabolism. Specific and&#xD;
      individualized therapies have not been established neither in the clinical routine nor in&#xD;
      controlled studies. The goal of this monocentric non-blinded non-placebo controlled phase IIb&#xD;
      study is the evaluation of the effectivity of anticonvulsive drugs specifically working on&#xD;
      the ion channels defective in some subtypes of EEs in order to establish a standard and&#xD;
      individualized therapy for these rare diseases based on the specific genetic defect.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      During the study, the sodium channel blockers phenytoin and lacosamide and the potassium&#xD;
      channel blocker kinidinsulfate will be given under standardized conditions to patients with&#xD;
      an early onset and pharmaco-resistant genetic epilepsy with and without mutations in the&#xD;
      potassium channels KCNT1 and KCNQ2 and the sodium channel gene SCN2A. The primary endpoint&#xD;
      will be a significant seizure reduction under trial medication compared to baseline.&#xD;
      Secondary endpoints will be the improvement of electroencephalographic characteristics of the&#xD;
      respective EEs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    no patients recruited&#xD;
  </why_stopped>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">August 2020</completion_date>
  <primary_completion_date type="Anticipated">May 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Treatment A - if no positive response: Treatment B</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction of seizures</measure>
    <time_frame>one week</time_frame>
    <description>Reduction of epileptic seizures within one treatment phase to 50% compared to baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduction of seizures stratified for genetic background</measure>
    <time_frame>one week</time_frame>
    <description>Reduction of epileptic seizures within one treatment phase to 50% compared to baseline stratified for three gene mutations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of epileptic activities or suppression phases</measure>
    <time_frame>one week</time_frame>
    <description>Reduction of epileptic activities or suppression phases in EEG</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Seizure, Epileptic</condition>
  <arm_group>
    <arm_group_label>Therapy regime</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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..</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Therapy regime</intervention_name>
    <description>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.</description>
    <arm_group_label>Therapy regime</arm_group_label>
    <other_name>two medical products given in a predefined order</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  highly active epilepsy (≥ 1 seizure per day)&#xD;
&#xD;
          -  epilepsy with onset 0-3 months of age&#xD;
&#xD;
          -  pharmaco-resistant epilepsy (2 or more standard anticonvulsive medications tried&#xD;
             before)&#xD;
&#xD;
          -  recently max. two stable anticonvulsive drugs for minimum 4 days before study start&#xD;
&#xD;
          -  patients under continuous monitoring control&#xD;
&#xD;
          -  patients younger than 1 year of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  high grade cardial rhythm disorders&#xD;
&#xD;
          -  severe liver, renal and electrolyte blood parameter changes&#xD;
&#xD;
          -  metabolic or lesional origin of epilepsy (metabolic screening results and cranial MRI&#xD;
             available)&#xD;
&#xD;
          -  parallel participation in other studies (must be finished two month before study&#xD;
             start)&#xD;
&#xD;
          -  missing informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>12 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Markus Wolff, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Children's Hospital Tübingen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universtiy Hospital</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>November 16, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2016</study_first_posted>
  <last_update_submitted>February 5, 2020</last_update_submitted>
  <last_update_submitted_qc>February 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Seizures</mesh_term>
    <mesh_term>Epilepsy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_type>Synopsis</doc_type>
      <doc_url>http://www.medizin.uni-tuebingen.de/kinder/de/abteilungen/cpcs/projekte/</doc_url>
    </study_doc>
  </study_docs>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02968966
org study id: AKF 357-0-0
nct id: NCT02968966
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Treatment A - if no positive response: Treatment B
primary purpose: Treatment
masking: None (Open Label)
measure: Reduction of seizures
time frame: one week
description: Reduction of epileptic seizures within one treatment phase to 50% compared to baseline
measure: Reduction of seizures stratified for genetic background
time frame: one week
description: Reduction of epileptic seizures within one treatment phase to 50% compared to baseline stratified for three gene mutations
measure: Reduction of epileptic activities or suppression phases
time frame: one week
description: Reduction of epileptic activities or suppression phases in EEG
arm group label: Therapy regime
arm group type: Experimental
description: 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..
intervention type: Other
intervention name: Therapy regime
description: 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.
arm group label: Therapy regime
other name: two medical products given in a predefined order
criteria: 
gender: All
minimum age: N/A
maximum age: 12 Months
healthy volunteers: No
last name: Markus Wolff, Dr.
role: Principal Investigator
affiliation: University Children's Hospital Tübingen
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Seizures
mesh term: Epilepsy
sharing ipd: No
study doc: 