xml: <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/NCT06023953</url>
    </required_header>
    <id_info>
      <org_study_id>RWE006</org_study_id>
      <nct_id>NCT06023953</nct_id>
    </id_info>
    <brief_title>Migraine With and Without Response to Remote Electrical Neuromodulation (REN) Treatment</brief_title>
    <official_title>Comparison of Migraine With and Without Aura in a Large Cohort: Disease Characteristics and Response to Remote Electrical Neuromodulation (REN) Treatment</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Theranica</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Theranica</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a Post-marketing study investigating the safety and efficacy of the acute treatment&#xD;
        of migraine with a Remote Electrical Neuromodulation (REN) device (Nerivio) in migraine&#xD;
        patients with and without aura, as well as characterizing demographic and attack&#xD;
        characteristic differences between migraine patients with and without aura.&#xD;
  &#xD;
        Safety will be assessed by the number and type of device-related adverse events. Efficacy&#xD;
        will be evaluated as a change in headache pain severity from baseline to 2 hours&#xD;
        post-treatment. Disease characteristics will look into demographic and attack differences&#xD;
        between patients with and without aura.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The REN device (Nerivio by Theranica, ISRAEL) is a neuromodulation device approved by the FDA&#xD;
        for acute and/or preventive treatment of migraine in patients 12 years old and above. It is a&#xD;
        wearable device applied to the upper arm. It stimulates C and Aδ noxious fibers using a&#xD;
        modulated, symmetrical, biphasic, square pulse with a pulse width of 400 μs, modulated&#xD;
        frequency of 100-120 Hz, and up to 40 mA output current which the patient can adjust. The REN&#xD;
        device is operated by a designated smartphone application that is downloaded to the user's&#xD;
        phone prior first use of the Nerivio device.&#xD;
  &#xD;
        As part of the sign-up process for the Nerivio app, all patients accept the terms of use&#xD;
        which specify that providing personal information is done on their own free will and that&#xD;
        their de-identified data may be used for research purposes. Users are not obligated to&#xD;
        provide personal information and could treat without providing any feedback. The app includes&#xD;
        a secured, personal migraine diary, which enables patients to record and track their&#xD;
        migraines and other headaches. At the beginning of each treatment, and again 2 hours after&#xD;
        the start of treatment, patients are prompted to record their symptoms, including the&#xD;
        presence or absence of aura, pain level (none, mild, moderate, severe), functional disability&#xD;
        (none, mild limitation, moderate limitation, severe limitation), presence of associated&#xD;
        symptoms (photophobia, phonophobia, and nausea), and an indication of which medications, if&#xD;
        any, were taken within that 2-hour time window.&#xD;
  &#xD;
        Post-marketing surveillance is designed to assess the safety and efficacy of REN in larger&#xD;
        and more diverse populations than in clinical trials and in various real-world environments&#xD;
        and situations. As a digital therapeutic device (i.e., electroceutical), the REN device&#xD;
        enables prospective collection of electronic patient-reported outcomes in real-world clinical&#xD;
        practice.&#xD;
  &#xD;
        This post-marketing RWE study investigates the safety and efficacy of the Nerivio treatment&#xD;
        in patients with and without aura by analyzing data from patients who used the Nerivio&#xD;
        device. The following outcomes will be assessed:&#xD;
  &#xD;
          1. - Safety - all adverse events that were reported during the study's period&#xD;
  &#xD;
          2. - Efficacy - pain relief, freedom from pain, improvement in functional disability, and&#xD;
             return to normal function (no disability) at 2 hours post-treatment 3 - Disease severity&#xD;
             -severe headache pain, presence of associated symptoms.&#xD;
  &#xD;
        Together, these objectives provide a comprehensive evaluation of the effect of REN as a&#xD;
        treatment for migraine with or without aura.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">July 1, 2023</start_date>
    <completion_date type="Actual">August 1, 2023</completion_date>
    <primary_completion_date type="Actual">July 30, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Consistent Headache Relief at 2 Hours Post-treatment</measure>
      <time_frame>2 hours</time_frame>
      <description>The proportion of subjects reporting headache relief at 2 hours post-treatment in at least 50% of all their treatments. Headache relief is defined as an improvement from severe or moderate pain to mild or no pain.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Device Related Adverse Events</measure>
      <time_frame>40 Months</time_frame>
      <description>Incidence of device-related adverse events reported by subjects</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Consistent Freedom From Headache at 2 Hours Post-treatment</measure>
      <time_frame>2 hours</time_frame>
      <description>The proportion of subjects reporting freedom from headache at 2 hours post-treatment in at least 50% of all their treatments. Pain freedom is defined as the disappearance of headache from severe, moderate, or mild headache at treatment initiation to no headache 2 hours later</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Severe Headache Pain during migraine attack</measure>
      <time_frame>2 hours</time_frame>
      <description>The proportion of subjects reporting severe headache pain in at least 50% of their attacks.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Associated Symptoms Relief</measure>
      <time_frame>2 hours</time_frame>
      <description>The proportion of subjects reporting each of the migraine-associated symptoms (photophobia, phonophobia, nausea) in at least 50% of their attacks.</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Actual">24446</enrollment>
    <condition>Migraine With Aura</condition>
    <condition>Migraine Without Aura</condition>
    <arm_group>
      <arm_group_label>Migraine with aura (MWA)</arm_group_label>
      <description>Patients with migraine who used the Nerivio device at least once and reported having aura in at least one treatment</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Migraine without aura (MWoA )</arm_group_label>
      <description>Patients with migraine who used the Nerivio device at least once and never reported having aura in any of their treatments</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Nerivio device</intervention_name>
      <description>REN treatment with Nerivio device</description>
      <arm_group_label>Migraine with aura (MWA)</arm_group_label>
      <arm_group_label>Migraine without aura (MWoA )</arm_group_label>
    </intervention>
    <eligibility>
      <study_pop>
        <textblock>
          Patients who were diagnosed with migraine by their HCP and were prescribed Nerivio for&#xD;
          treatment of acute migraine&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 12 years old and above&#xD;
  &#xD;
            -  REN users across the USA who created Nerivio accounts between October 2019 and&#xD;
               February 2023.&#xD;
  &#xD;
            -  Treated acute migraine at least once with Nerivio device&#xD;
  &#xD;
            -  Reported at least one treatment questionnaire at T=0h and T=2h&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Treatments shorter than 30 minutes&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>12 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Alit Stark Inbar, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Theranica Bio-Electronics Ltd</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Theranica Bio-Electronics Ltd</name>
        <address>
          <city>Netanya</city>
          <zip>4520438</zip>
          <country>Israel</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Israel</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 29, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 5, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>migraine</keyword>
    <keyword>Nerivio</keyword>
    <keyword>REN</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Migraine Disorders</mesh_term>
      <mesh_term>Epilepsy</mesh_term>
      <mesh_term>Migraine without Aura</mesh_term>
      <mesh_term>Migraine with Aura</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06023953
  org study id: RWE006
  nct id: NCT06023953
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: No
  This is a Post-marketing study investigating the safety and efficacy of the acute treatment
        of migraine with a Remote Electrical Neuromodulation (REN) device (Nerivio) in migraine
        patients with and without aura, as well as characterizing demographic and attack
        characteristic differences between migraine patients with and without aura.
  
        Safety will be assessed by the number and type of device-related adverse events. Efficacy
        will be evaluated as a change in headache pain severity from baseline to 2 hours
        post-treatment. Disease characteristics will look into demographic and attack differences
        between patients with and without aura.
  The REN device (Nerivio by Theranica, ISRAEL) is a neuromodulation device approved by the FDA
        for acute and/or preventive treatment of migraine in patients 12 years old and above. It is a
        wearable device applied to the upper arm. It stimulates C and Aδ noxious fibers using a
        modulated, symmetrical, biphasic, square pulse with a pulse width of 400 μs, modulated
        frequency of 100-120 Hz, and up to 40 mA output current which the patient can adjust. The REN
        device is operated by a designated smartphone application that is downloaded to the user's
        phone prior first use of the Nerivio device.
  
        As part of the sign-up process for the Nerivio app, all patients accept the terms of use
        which specify that providing personal information is done on their own free will and that
        their de-identified data may be used for research purposes. Users are not obligated to
        provide personal information and could treat without providing any feedback. The app includes
        a secured, personal migraine diary, which enables patients to record and track their
        migraines and other headaches. At the beginning of each treatment, and again 2 hours after
        the start of treatment, patients are prompted to record their symptoms, including the
        presence or absence of aura, pain level (none, mild, moderate, severe), functional disability
        (none, mild limitation, moderate limitation, severe limitation), presence of associated
        symptoms (photophobia, phonophobia, and nausea), and an indication of which medications, if
        any, were taken within that 2-hour time window.
  
        Post-marketing surveillance is designed to assess the safety and efficacy of REN in larger
        and more diverse populations than in clinical trials and in various real-world environments
        and situations. As a digital therapeutic device (i.e., electroceutical), the REN device
        enables prospective collection of electronic patient-reported outcomes in real-world clinical
        practice.
  
        This post-marketing RWE study investigates the safety and efficacy of the Nerivio treatment
        in patients with and without aura by analyzing data from patients who used the Nerivio
        device. The following outcomes will be assessed:
  
          1. - Safety - all adverse events that were reported during the study's period
  
          2. - Efficacy - pain relief, freedom from pain, improvement in functional disability, and
             return to normal function (no disability) at 2 hours post-treatment 3 - Disease severity
             -severe headache pain, presence of associated symptoms.
  
        Together, these objectives provide a comprehensive evaluation of the effect of REN as a
        treatment for migraine with or without aura.
  observational model: Cohort
  time perspective: Prospective
  measure: Consistent Headache Relief at 2 Hours Post-treatment
  time frame: 2 hours
  description: The proportion of subjects reporting headache relief at 2 hours post-treatment in at least 50% of all their treatments. Headache relief is defined as an improvement from severe or moderate pain to mild or no pain.
  measure: Device Related Adverse Events
  time frame: 40 Months
  description: Incidence of device-related adverse events reported by subjects
  measure: Consistent Freedom From Headache at 2 Hours Post-treatment
  time frame: 2 hours
  description: The proportion of subjects reporting freedom from headache at 2 hours post-treatment in at least 50% of all their treatments. Pain freedom is defined as the disappearance of headache from severe, moderate, or mild headache at treatment initiation to no headache 2 hours later
  measure: Severe Headache Pain during migraine attack
  time frame: 2 hours
  description: The proportion of subjects reporting severe headache pain in at least 50% of their attacks.
  measure: Associated Symptoms Relief
  time frame: 2 hours
  description: The proportion of subjects reporting each of the migraine-associated symptoms (photophobia, phonophobia, nausea) in at least 50% of their attacks.
  arm group label: Migraine with aura (MWA)
  description: Patients with migraine who used the Nerivio device at least once and reported having aura in at least one treatment
  arm group label: Migraine without aura (MWoA )
  description: Patients with migraine who used the Nerivio device at least once and never reported having aura in any of their treatments
  intervention type: Device
  intervention name: Nerivio device
  description: REN treatment with Nerivio device
  arm group label: Migraine with aura (MWA)
  arm group label: Migraine without aura (MWoA )
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 12 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Alit Stark Inbar, PhD
  role: Principal Investigator
  affiliation: Theranica Bio-Electronics Ltd
  facility: 
  country: Israel
  responsible party type: Sponsor
  mesh term: Migraine Disorders
  mesh term: Epilepsy
  mesh term: Migraine without Aura
  mesh term: Migraine with Aura
  sharing ipd: No