<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/NCT01667250</url>
  </required_header>
  <id_info>
    <org_study_id>M-US-02</org_study_id>
    <nct_id>NCT01667250</nct_id>
  </id_info>
  <brief_title>Non-Invasive Neurostimulation for the Prevention of Chronic Migraine</brief_title>
  <official_title>Non-Invasive Neurostimulation of the Vagus Nerve With the GammaCore Device for the Prevention of Chronic Migraine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ElectroCore INC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ElectroCore INC</source>
  <brief_summary>
    <textblock>
      The purpose of this multi-center, prospective, double-blind, randomized, sham-controlled&#xD;
      pilot study is to study feasibility and collect preliminary clinical data related to the&#xD;
      safety and clinical benefits of daily use of non-invasive vagal nerve stimulation with the&#xD;
      GammaCore device for the prevention of chronic migraine, and to support the development and&#xD;
      approval of a larger pivotal study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">May 2014</completion_date>
  <primary_completion_date type="Actual">May 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety - Number of Participants With Adverse Events</measure>
    <time_frame>Up to 8 weeks - duration of the Randomized period</time_frame>
    <description>Safety was assessed by collecting Adverse Effects</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Headache Days</measure>
    <time_frame>Run-in period (4 weeks no treatment) and Randomized period (8 weeks)</time_frame>
    <description>Mean change in headache days. Change between 4 week run in period to the 8 weeks randomized period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe</measure>
    <time_frame>Run-in (4 weeks no treatment) and Randomized (8 weeks)</time_frame>
    <description>Peak severity per headache day was reported each headache day in the subject diary. Pain was reported as mild, moderate or severe. Whereas as mild = least severe and severe = most severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of Pain Relief Medication</measure>
    <time_frame>Randomized period - 8 weeks</time_frame>
    <description>All abortive headache medication taken during randomized period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Quality of Life Short Form Survey (SF-12)</measure>
    <time_frame>Run-in (4 weeks) and Randomized period (8 weeks)</time_frame>
    <description>The Quality of Life Short Form Survey (SF-12) is a multipurpose short form survey with 12 questions that are combined, scored and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. The SF-12 is weighted and summed to provide easily interpretable scales for physical and mental health. Physical and Mental Health Composite Scores (PCS &amp; MCS) are computed using the scores of the twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.&#xD;
SF-12 were recorded in the subject diary at the Phase 1 follow-up visit (week 4) and during Phase 2 randomized period at week 4 and week 8.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">59</enrollment>
  <condition>Chronic Migraine</condition>
  <arm_group>
    <arm_group_label>GammaCore Active Device</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will use an Active GammaCore Device</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GammaCore Sham Device</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>GammaCore Active Device</intervention_name>
    <arm_group_label>GammaCore Active Device</arm_group_label>
    <arm_group_label>GammaCore Sham Device</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>GammaCore Sham Device</intervention_name>
    <arm_group_label>GammaCore Sham Device</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Is between the ages of 18 and 65 years.&#xD;
&#xD;
          -  Has been previously diagnosed as suffering from migraine, in accordance with the&#xD;
             ICHD-2 Classification criteria (2nd), with or without aura.&#xD;
&#xD;
          -  Experiences at least 15 headache days per month (over the last 3 months).&#xD;
&#xD;
          -  Has age of onset of migraine less than 50 years old.&#xD;
&#xD;
          -  Agrees not to use any migraine prevention treatments (including Botox injections)&#xD;
             and/or medications (exclusive of medications taken for acute relief of migraine&#xD;
             symptoms).&#xD;
&#xD;
          -  Is able to provide written Informed Consent&#xD;
&#xD;
          -  Agrees to refrain from changing the type or dosage of any prophylactic medications for&#xD;
             indications other than chronic migraine that in the opinion of the clinician may&#xD;
             interfere with the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a history of aneurysm, intracranial hemorrhage, brain tumors or significant head&#xD;
             trauma.&#xD;
&#xD;
          -  Has a lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal&#xD;
             anatomy at the GammaCore treatment site.&#xD;
&#xD;
          -  Has known or suspected severe atherosclerotic cardiovascular disease, severe carotid&#xD;
             artery disease (e.g. bruits or history of TIA or CVA), congestive heart failure (CHF),&#xD;
             known severe coronary artery disease or recent myocardial infarction.&#xD;
&#xD;
          -  Has an abnormal baseline ECG (e.g. second and third degree heart block, atrial&#xD;
             fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular&#xD;
             fibrillation, or clinically significant premature ventricular contraction)&#xD;
&#xD;
          -  Has had a previous bilateral, right, or left cervical vagotomy.&#xD;
&#xD;
          -  Has uncontrolled high blood pressure.&#xD;
&#xD;
          -  Is currently implanted with an electrical and/or neurostimulator device, including but&#xD;
             not limited to cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain&#xD;
             stimulator, spinal stimulator, bone growth stimulator, or cochlear implant.&#xD;
&#xD;
          -  Has a history of carotid endarterectomy or vascular neck surgery on the right side.&#xD;
&#xD;
          -  Has been implanted with metal cervical spine hardware or has a metallic implant near&#xD;
             the GammaCore stimulation site.&#xD;
&#xD;
          -  Has a recent or repeated history of syncope.&#xD;
&#xD;
          -  Has a recent or repeated history of seizure.&#xD;
&#xD;
          -  Has a known history or suspicion of substance abuse or addiction.&#xD;
&#xD;
          -  Has had a surgery for migraine prevention.&#xD;
&#xD;
          -  Has received Botox injections for migraine prevention within the past 6 months.&#xD;
&#xD;
          -  Has taken medications for migraine prophylaxis in the previous 30 days.&#xD;
&#xD;
          -  In the opinion of the investigator/research staff the subject is incapable of&#xD;
             operating the GammaCore device as intended and performing the data collection&#xD;
             procedures.&#xD;
&#xD;
          -  Is pregnant, nursing, thinking of becoming pregnant in the next 9 months, or of&#xD;
             childbearing years and is unwilling to use an accepted form of birth control.&#xD;
&#xD;
          -  Is participating in any other therapeutic clinical investigation or has participated&#xD;
             in a clinical trial in the preceding 30 days.&#xD;
&#xD;
          -  Belongs to a vulnerable population or has any condition such that his or her ability&#xD;
             to provide informed consent, comply with follow-up requirements, or provide&#xD;
             self-assessments is compromised (e.g., homeless, developmentally disabled, prisoner).&#xD;
&#xD;
          -  Is a relative of or an employee of the investigator or the clinical study site.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UCSF Headache Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michigan Head Pain &amp; Neurological Institute</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Headache Care Center</name>
      <address>
        <city>Springfield</city>
        <state>Missouri</state>
        <zip>65807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Headache Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Headache Institute</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson Headache Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/24607501</url>
    <description>Effect of noninvasive vagus nerve stimulation on acute migraine: An open-label pilot study</description>
  </link>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>March 8, 2018</results_first_submitted>
  <results_first_submitted_qc>May 22, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">June 20, 2018</results_first_posted>
  <disposition_first_submitted>February 17, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>February 17, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">March 16, 2016</disposition_first_posted>
  <last_update_submitted>May 22, 2018</last_update_submitted>
  <last_update_submitted_qc>May 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 20, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>vagus nerve stimulation</keyword>
  <keyword>vagal nerve stimulation</keyword>
  <keyword>nVNS</keyword>
  <keyword>VNS</keyword>
  <keyword>chronic migraine</keyword>
  <keyword>migraine</keyword>
  <keyword>non invasive</keyword>
  <keyword>gammacore</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Migraine Disorders</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>GammaCore Active Device</title>
          <description>Subjects will use an Active GammaCore Device&#xD;
GammaCore Active Device</description>
        </group>
        <group group_id="P2">
          <title>GammaCore Sham Device</title>
          <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
        </group>
        <group group_id="P3">
          <title>No Treatment (run-in, Enrollment Period)</title>
          <description>The run-in period was 1 month, Subject who did not fulfill the inclusion and/or exclusion criteria was not randomized to the treatment groups</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Run-in (no Treatment)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="73"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Randomised Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="29"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Randomized population</population>
      <group_list>
        <group group_id="B1">
          <title>GammaCore Active Device</title>
          <description>Subjects will use an Active GammaCore Device&#xD;
GammaCore Active Device</description>
        </group>
        <group group_id="B2">
          <title>GammaCore Sham Device</title>
          <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="59"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.7" lower_limit="18.2" upper_limit="65.2"/>
                    <measurement group_id="B2" value="41.0" lower_limit="20.0" upper_limit="60.9"/>
                    <measurement group_id="B3" value="40" lower_limit="18.2" upper_limit="65.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="53"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Safety - Number of Participants With Adverse Events</title>
        <description>Safety was assessed by collecting Adverse Effects</description>
        <time_frame>Up to 8 weeks - duration of the Randomized period</time_frame>
        <population>Randomized population</population>
        <group_list>
          <group group_id="O1">
            <title>GammaCore Active Device</title>
            <description>Subjects will use an Active GammaCore Device&#xD;
GammaCore Active Device</description>
          </group>
          <group group_id="O2">
            <title>GammaCore Sham Device</title>
            <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety - Number of Participants With Adverse Events</title>
          <description>Safety was assessed by collecting Adverse Effects</description>
          <population>Randomized population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Headache Days</title>
        <description>Mean change in headache days. Change between 4 week run in period to the 8 weeks randomized period.</description>
        <time_frame>Run-in period (4 weeks no treatment) and Randomized period (8 weeks)</time_frame>
        <population>Data missing for 1 subject in each treatment group</population>
        <group_list>
          <group group_id="O1">
            <title>GammaCore Active Device</title>
            <description>Subjects will use an Active GammaCore Device&#xD;
GammaCore Active Device</description>
          </group>
          <group group_id="O2">
            <title>GammaCore Sham Device</title>
            <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Headache Days</title>
          <description>Mean change in headache days. Change between 4 week run in period to the 8 weeks randomized period.</description>
          <population>Data missing for 1 subject in each treatment group</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="5.92"/>
                    <measurement group_id="O2" value="-0.2" spread="3.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe</title>
        <description>Peak severity per headache day was reported each headache day in the subject diary. Pain was reported as mild, moderate or severe. Whereas as mild = least severe and severe = most severe.</description>
        <time_frame>Run-in (4 weeks no treatment) and Randomized (8 weeks)</time_frame>
        <population>Randomized population</population>
        <group_list>
          <group group_id="O1">
            <title>GammaCore Active Device</title>
            <description>Subjects will use an Active GammaCore Device&#xD;
GammaCore Active Device</description>
          </group>
          <group group_id="O2">
            <title>GammaCore Sham Device</title>
            <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe</title>
          <description>Peak severity per headache day was reported each headache day in the subject diary. Pain was reported as mild, moderate or severe. Whereas as mild = least severe and severe = most severe.</description>
          <population>Randomized population</population>
          <units>Headache days</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Run-in Mild</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="167"/>
                    <measurement group_id="O2" value="131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Run-in Moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="297"/>
                    <measurement group_id="O2" value="330"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Run-in Severe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="190"/>
                    <measurement group_id="O2" value="225"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Randomized Mild</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="297"/>
                    <measurement group_id="O2" value="250"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Randomized Moderate</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="443"/>
                    <measurement group_id="O2" value="511"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Randomized Severe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="274"/>
                    <measurement group_id="O2" value="395"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Use of Pain Relief Medication</title>
        <description>All abortive headache medication taken during randomized period</description>
        <time_frame>Randomized period - 8 weeks</time_frame>
        <population>Randomized population</population>
        <group_list>
          <group group_id="O1">
            <title>GammaCore Active Device</title>
            <description>Subjects will use an Active GammaCore Device GammaCore Active Device</description>
          </group>
          <group group_id="O2">
            <title>GammaCore Sham Device</title>
            <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Use of Pain Relief Medication</title>
          <description>All abortive headache medication taken during randomized period</description>
          <population>Randomized population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subjects taking abortive medication</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subjects taking no abortive medication</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subjects with no data</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Quality of Life Short Form Survey (SF-12)</title>
        <description>The Quality of Life Short Form Survey (SF-12) is a multipurpose short form survey with 12 questions that are combined, scored and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. The SF-12 is weighted and summed to provide easily interpretable scales for physical and mental health. Physical and Mental Health Composite Scores (PCS &amp; MCS) are computed using the scores of the twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.&#xD;
SF-12 were recorded in the subject diary at the Phase 1 follow-up visit (week 4) and during Phase 2 randomized period at week 4 and week 8.</description>
        <time_frame>Run-in (4 weeks) and Randomized period (8 weeks)</time_frame>
        <population>Randomized period</population>
        <group_list>
          <group group_id="O1">
            <title>GammaCore Active Device</title>
            <description>Subjects will use an Active GammaCore Device&#xD;
GammaCore Active Device</description>
          </group>
          <group group_id="O2">
            <title>GammaCore Sham Device</title>
            <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Quality of Life Short Form Survey (SF-12)</title>
          <description>The Quality of Life Short Form Survey (SF-12) is a multipurpose short form survey with 12 questions that are combined, scored and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. The SF-12 is weighted and summed to provide easily interpretable scales for physical and mental health. Physical and Mental Health Composite Scores (PCS &amp; MCS) are computed using the scores of the twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.&#xD;
SF-12 were recorded in the subject diary at the Phase 1 follow-up visit (week 4) and during Phase 2 randomized period at week 4 and week 8.</description>
          <population>Randomized period</population>
          <units>Score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Run-in PCS score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.9" spread="9.62"/>
                    <measurement group_id="O2" value="35.6" spread="10.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Randomized period PCS score 4 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.0" spread="9.25"/>
                    <measurement group_id="O2" value="37.5" spread="12.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Randomized period PCS scores 8 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.3" spread="8.01"/>
                    <measurement group_id="O2" value="38.0" spread="10.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Run-in MCS scores</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.5" spread="11.41"/>
                    <measurement group_id="O2" value="45.8" spread="10.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Randomized period MCS scores 4 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.7" spread="10.53"/>
                    <measurement group_id="O2" value="45.8" spread="11.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Randomized period MCS scores 8 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.5" spread="9.95"/>
                    <measurement group_id="O2" value="44.3" spread="12.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 8 weeks - duration of the Randomized period</time_frame>
      <group_list>
        <group group_id="E1">
          <title>GammaCore Active Device</title>
          <description>Subjects will use an Active GammaCore Device&#xD;
GammaCore Active Device</description>
        </group>
        <group group_id="E2">
          <title>GammaCore Sham Device</title>
          <description>Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Worsening of Headache Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Intermittent Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>General malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Mild pains in head and right arm</sub_title>
                <description>Open label - phase 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Altered sensations (brain zaps)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Migratory Paresthesia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Right arm (hand) tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Right eye twitching</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Lip twiching</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Exacerbated migraine</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Lip numbness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Atypical migraine pain with associated blackouts</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Worsening of migraine</sub_title>
                <description>Open label - phase 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Severe migraine</sub_title>
                <description>Open label - phase 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Blister at treatment site</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rash at treatment site</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Itching</sub_title>
                <description>Open label - phase 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blisters at treatment site</sub_title>
                <description>Open label - phase 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rash/Blister at treatment site</sub_title>
                <description>Open label - phase 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Redness at treatment site</sub_title>
                <description>Open label - phase 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <description>Open label - phase 3</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Clinical Affairs</name_or_title>
      <organization>electroCore LLC</organization>
      <phone>+1 973 355 6683</phone>
      <email>clinical@electrocorellc.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01667250
org study id: M-US-02
nct id: NCT01667250
lead sponsor: 
The purpose of this multi-center, prospective, double-blind, randomized, sham-controlled
      pilot study is to study feasibility and collect preliminary clinical data related to the
      safety and clinical benefits of daily use of non-invasive vagal nerve stimulation with the
      GammaCore device for the prevention of chronic migraine, and to support the development and
      approval of a larger pivotal study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: Safety - Number of Participants With Adverse Events
time frame: Up to 8 weeks - duration of the Randomized period
description: Safety was assessed by collecting Adverse Effects
measure: Mean Change in Headache Days
time frame: Run-in period (4 weeks no treatment) and Randomized period (8 weeks)
description: Mean change in headache days. Change between 4 week run in period to the 8 weeks randomized period.
measure: Total Number of Headache Days Per Arm With Peak Severity of Mild, Moderate, or Severe
time frame: Run-in (4 weeks no treatment) and Randomized (8 weeks)
description: Peak severity per headache day was reported each headache day in the subject diary. Pain was reported as mild, moderate or severe. Whereas as mild = least severe and severe = most severe.
measure: Use of Pain Relief Medication
time frame: Randomized period - 8 weeks
description: All abortive headache medication taken during randomized period
measure: Mean Change in Quality of Life Short Form Survey (SF-12)
time frame: Run-in (4 weeks) and Randomized period (8 weeks)
description: The Quality of Life Short Form Survey (SF-12) is a multipurpose short form survey with 12 questions that are combined, scored and weighted to create two scales that provide glimpses into mental and physical functioning and overall health-related-quality of life. The SF-12 is weighted and summed to provide easily interpretable scales for physical and mental health. Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of the twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
SF-12 were recorded in the subject diary at the Phase 1 follow-up visit (week 4) and during Phase 2 randomized period at week 4 and week 8.
arm group label: GammaCore Active Device
arm group type: Active Comparator
description: Subjects will use an Active GammaCore Device
arm group label: GammaCore Sham Device
arm group type: Sham Comparator
description: Subjects who treat with the gammacore sham device in Phase 2 will receive the active gammacore treatment during phase 3 (active treatment) of this study.
intervention type: Device
intervention name: GammaCore Active Device
arm group label: GammaCore Active Device
arm group label: GammaCore Sham Device
intervention type: Device
intervention name: GammaCore Sham Device
arm group label: GammaCore Sham Device
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.ncbi.nlm.nih.gov/pubmed/24607501
description: Effect of noninvasive vagus nerve stimulation on acute migraine: An open-label pilot study
responsible party type: Sponsor
mesh term: Migraine Disorders
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 