<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/NCT01679314</url>
  </required_header>
  <id_info>
    <org_study_id>AC-001</org_study_id>
    <nct_id>NCT01679314</nct_id>
  </id_info>
  <brief_title>Study to Compare (COPD) Assessment Test in COPD Stage III and IV in a Prophylactic Treatment</brief_title>
  <official_title>A Prospective, Single Site, Randomized, Controlled, Parallel Group Study in Subjects With Chronic Obstructive Pulmonary Disease (COPD) Stage III and IV Using AlphaCore or Sham (Control, Not Active) as a Prophylactic Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ElectroCore INC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ElectroCore INC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will assess the treatment of patients with Chronic Obstructive Pulmonary Disease&#xD;
      (COPD) stage III and IV who will self administer the AlphaCore stimulation three times a day&#xD;
      over a course of 2 months. Patients will either receive an active AlphaCore device or a Sham&#xD;
      device during these two months while not knowing which device they have been provided. At the&#xD;
      end of the two months, all patients will be asked to continue in the study for another 2&#xD;
      months to self administer with the active AlphaCore device. Subjects will complete diaries at&#xD;
      home on their breathing and quality of life and will return to the clinic monthly for&#xD;
      assessment by the investigator.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PERFORMANCE AND SAFETY VARIABLES:&#xD;
&#xD;
      The primary efficacy endpoint for this study is the total Chronic obstructive pulmonary&#xD;
      disease (COPD) Assessment Test (CAT) score change from baseline to the 8 week follow-up&#xD;
      period comparing the two device groups.&#xD;
&#xD;
      Secondary efficacy endpoints will be the mean difference from baseline to the 8 week&#xD;
      follow-up for the following assessments: Medical Research Council (MRC) dyspnoea scale, 6&#xD;
      minutes walking test and Forced Expiratory Volume in one second (FEV1)&#xD;
&#xD;
      Safety Variables:&#xD;
&#xD;
      Each subject will be assessed throughout the study for Adverse Events and at the last visit&#xD;
      (4 months) subjects will undergo another physical examination including vital signs and blood&#xD;
      pressure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">May 2013</completion_date>
  <primary_completion_date type="Actual">January 2013</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>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores (Quality of Life and Symptoms) Changes Within a Treatment Period and Comparison Between the Two Groups</measure>
    <time_frame>8 weeks</time_frame>
    <description>Chronic obstructive pulmonary disease Assessment Test (CAT) scores (Quality of life and symptoms) changes within a treatment period and comparison between the two groups. Eight (8) questions. The scale is rated from 0 to 5, min = 0, max = 5. Low rates = better, high rates = worse. Mean change in the period 8 weeks versus baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Borg Dyspnoea Scores</measure>
    <time_frame>Baseline vs 8 weeks</time_frame>
    <description>Borg dyspnoea scale (Physical activity test): 0 - 11 (Not at all effected - Extremely effected) The result show the change between the the treatment groups from baseline to week 8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change 6 Minutes Walking Test</measure>
    <time_frame>Baseline vs 8 weeks</time_frame>
    <description>Six minutes walking test: Measure distance (meter) after 6 minutes walk. Change from Baseline between treatment groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Forced Expiratory Volume (FEV1)</measure>
    <time_frame>Baseline vs 8 weeks</time_frame>
    <description>Forced Expiratory Volume (FEV1): Maximum volume that can be exhaled in the first second - after maximum inhalation.&#xD;
Change from baseline to week 8 between treatment groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in EuroQol, 5 Questions and 3 Levels (EQ5D-3L)</measure>
    <time_frame>Baseline vs 8 weeks</time_frame>
    <description>The EQ-5D-3L (EuroQoL 5 questions and 3 answering levels) during the run-in period will be compared with the EQ-5D-3L during the treatment period. And treatment period will be compared to open label.&#xD;
Rating of questions Level 1 no problems Level 2 some problems Level 3 Significant problems Worst case is 15 points and best case is 5 points using index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With Adverse Events (AE)</measure>
    <time_frame>Throughout the course of the study (baseline to the 4 month follow-up visit)</time_frame>
    <description>All AEs including but not limited to events reported by the subject or reported in response to an open question by the Clinical Investigator or member of this team, which fall into any of the above definitions must be recorded as an AE in the Case Report Form (CRF) and should include the following information.&#xD;
Brief description of the event (diagnosis)&#xD;
Start date (and time, if relevant)&#xD;
Stop date (and time, if relevant) (or resolution)&#xD;
Severity&#xD;
Action taken regarding the medical device&#xD;
Opinion on causality&#xD;
Seriousness&#xD;
Outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Change in EuroQol, 5 Questions and 3 Levels (EQ-5D-3L), Visual Analogue Scale (VAS)</measure>
    <time_frame>Baseline vs 8 weeks</time_frame>
    <description>Visual analogue scale (VAS) 0-100 where 0 is the worst imaginable health state and 100 the best imaginable health state</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>Active AlphaCore device</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>AlphaCore active stimulation treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham AlphaCore device</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>AlphaCore sham device</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>AlphaCore device</intervention_name>
    <description>Each study group will go under the same treatment regimen and assessments.</description>
    <arm_group_label>Active AlphaCore device</arm_group_label>
    <arm_group_label>Sham AlphaCore device</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 40-75 years&#xD;
&#xD;
          -  Diagnosed Chronic obstructive pulmonary disease(COPD) stage III and IV according to&#xD;
             Global Initiative for chronic obstructive lung disease (GOLD) guideline&#xD;
&#xD;
          -  Forced expiratory volume in one second (FEV 1) &lt; 50%&#xD;
&#xD;
          -  Forced expiratory volume in one second (FEV1/Forced expiratory vital capacity (FVC) &lt;&#xD;
             70%&#xD;
&#xD;
          -  Signed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in other clinical trials (drug or medical device) 30 days prior to start&#xD;
             of this study&#xD;
&#xD;
          -  Subject is unable to comply with the procedures if the protocol for the study or any&#xD;
             other reason judged by the Investigator that could interfere with the study assessment&#xD;
             or follow-up&#xD;
&#xD;
          -  Has an abscess or other infection or lesion (including lymphadenopathy) at the&#xD;
             AlphaCore® treatment site.&#xD;
&#xD;
          -  Is currently implanted with an electrical and/or neurostimulator device, including but&#xD;
             not limited to cardiac pacemaker, 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;
          -  Right side or bilateral vagotomy&#xD;
&#xD;
          -  Has a recent or repeated history of syncope.&#xD;
&#xD;
          -  Has a recent or repeated history of seizures.&#xD;
&#xD;
          -  Pregnant or breast feeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Matthias John, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Praxis für Pneumologie am Asklepios Klinikum Uckermark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Praxis fur Pneumologie am Asklepios Klinikum Uckermark</name>
      <address>
        <city>Schwedt</city>
        <state>Oder</state>
        <zip>D-16303</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 6, 2012</study_first_posted>
  <results_first_submitted>January 16, 2015</results_first_submitted>
  <results_first_submitted_qc>May 2, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 9, 2016</results_first_posted>
  <last_update_submitted>May 2, 2016</last_update_submitted>
  <last_update_submitted_qc>May 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 9, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>vagus nerve stimulation</keyword>
  <keyword>vagal nerve stimulation</keyword>
  <keyword>nVNS</keyword>
  <keyword>VNS</keyword>
  <keyword>non invasive</keyword>
  <keyword>gammacore</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No description</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Active AlphaCore Device</title>
          <description>AlphaCore active stimulation treatment&#xD;
AlphaCore device: Each study group will go under the same treatment regimen and assessments.</description>
        </group>
        <group group_id="P2">
          <title>Sham AlphaCore Device</title>
          <description>AlphaCore sham device&#xD;
AlphaCore device: Each study group will go under the same treatment regimen and assessments.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="28"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Active AlphaCore Device</title>
          <description>AlphaCore active stimulation treatment&#xD;
AlphaCore device: Each study group will go under the same treatment regimen and assessments.</description>
        </group>
        <group group_id="B2">
          <title>Sham AlphaCore Device</title>
          <description>AlphaCore sham device&#xD;
AlphaCore device: Each study group will go under the same treatment regimen and assessments.</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="26"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="54"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.2" spread="7.2"/>
                    <measurement group_id="B2" value="58.0" spread="7.6"/>
                    <measurement group_id="B3" value="59.5" spread="7.5"/>
                  </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="9"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores (Quality of Life and Symptoms) Changes Within a Treatment Period and Comparison Between the Two Groups</title>
        <description>Chronic obstructive pulmonary disease Assessment Test (CAT) scores (Quality of life and symptoms) changes within a treatment period and comparison between the two groups. Eight (8) questions. The scale is rated from 0 to 5, min = 0, max = 5. Low rates = better, high rates = worse. Mean change in the period 8 weeks versus baseline.</description>
        <time_frame>8 weeks</time_frame>
        <population>One patient in the Active AlphaCore device Group missing data at 8 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Active AlphaCore Device</title>
            <description>AlphaCore active stimulation treatment&#xD;
AlphaCore device: Each study group will go under the same treatment regimen and assessments.</description>
          </group>
          <group group_id="O2">
            <title>Sham AlphaCore Device</title>
            <description>AlphaCore sham device&#xD;
AlphaCore device: Each study group will go under the same treatment regimen and assessments.</description>
          </group>
        </group_list>
        <measure>
          <title>Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores (Quality of Life and Symptoms) Changes Within a Treatment Period and Comparison Between the Two Groups</title>
          <description>Chronic obstructive pulmonary disease Assessment Test (CAT) scores (Quality of life and symptoms) changes within a treatment period and comparison between the two groups. Eight (8) questions. The scale is rated from 0 to 5, min = 0, max = 5. Low rates = better, high rates = worse. Mean change in the period 8 weeks versus baseline.</description>
          <population>One patient in the Active AlphaCore device Group missing data at 8 weeks.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" lower_limit="-3.2" upper_limit="0.6"/>
                    <measurement group_id="O2" value="-0.9" lower_limit="-2.7" upper_limit="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Borg Dyspnoea Scores</title>
        <description>Borg dyspnoea scale (Physical activity test): 0 - 11 (Not at all effected - Extremely effected) The result show the change between the the treatment groups from baseline to week 8</description>
        <time_frame>Baseline vs 8 weeks</time_frame>
        <population>One subject in the Active AlphaCore device Group missing data at 8 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Active AlphaCore Device</title>
            <description>Active AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
          <group group_id="O2">
            <title>Sham AlphaCore Device</title>
            <description>Sham AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Borg Dyspnoea Scores</title>
          <description>Borg dyspnoea scale (Physical activity test): 0 - 11 (Not at all effected - Extremely effected) The result show the change between the the treatment groups from baseline to week 8</description>
          <population>One subject in the Active AlphaCore device Group missing data at 8 weeks.</population>
          <units>Scores 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="25"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="2.0"/>
                    <measurement group_id="O2" value="0.4" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change 6 Minutes Walking Test</title>
        <description>Six minutes walking test: Measure distance (meter) after 6 minutes walk. Change from Baseline between treatment groups</description>
        <time_frame>Baseline vs 8 weeks</time_frame>
        <population>One patient in the Active AlphaCore group is missing data at week 8</population>
        <group_list>
          <group group_id="O1">
            <title>Active AlphaCore Device</title>
            <description>Active AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
          <group group_id="O2">
            <title>Sham AlphaCore Device</title>
            <description>Sham AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
        </group_list>
        <measure>
          <title>Change 6 Minutes Walking Test</title>
          <description>Six minutes walking test: Measure distance (meter) after 6 minutes walk. Change from Baseline between treatment groups</description>
          <population>One patient in the Active AlphaCore group is missing data at week 8</population>
          <units>Meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.1" spread="61.5"/>
                    <measurement group_id="O2" value="12.6" spread="55.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Forced Expiratory Volume (FEV1)</title>
        <description>Forced Expiratory Volume (FEV1): Maximum volume that can be exhaled in the first second - after maximum inhalation.&#xD;
Change from baseline to week 8 between treatment groups</description>
        <time_frame>Baseline vs 8 weeks</time_frame>
        <population>One subject in the Active AlphaCore group missing data at week 8</population>
        <group_list>
          <group group_id="O1">
            <title>Active AlphaCore Device</title>
            <description>Active AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
          <group group_id="O2">
            <title>Sham AlphaCore Device</title>
            <description>Sham AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Forced Expiratory Volume (FEV1)</title>
          <description>Forced Expiratory Volume (FEV1): Maximum volume that can be exhaled in the first second - after maximum inhalation.&#xD;
Change from baseline to week 8 between treatment groups</description>
          <population>One subject in the Active AlphaCore group missing data at week 8</population>
          <units>Percentage of predicted value</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.7" spread="8.8"/>
                    <measurement group_id="O2" value="29.7" spread="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.0" spread="9.5"/>
                    <measurement group_id="O2" value="31.0" spread="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in EuroQol, 5 Questions and 3 Levels (EQ5D-3L)</title>
        <description>The EQ-5D-3L (EuroQoL 5 questions and 3 answering levels) during the run-in period will be compared with the EQ-5D-3L during the treatment period. And treatment period will be compared to open label.&#xD;
Rating of questions Level 1 no problems Level 2 some problems Level 3 Significant problems Worst case is 15 points and best case is 5 points using index</description>
        <time_frame>Baseline vs 8 weeks</time_frame>
        <population>One patient in the Active AlphaCore group is missing data at 8 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Active AlphaCore Device</title>
            <description>Active AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
          <group group_id="O2">
            <title>Sham AlphaCore Device</title>
            <description>Sham AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in EuroQol, 5 Questions and 3 Levels (EQ5D-3L)</title>
          <description>The EQ-5D-3L (EuroQoL 5 questions and 3 answering levels) during the run-in period will be compared with the EQ-5D-3L during the treatment period. And treatment period will be compared to open label.&#xD;
Rating of questions Level 1 no problems Level 2 some problems Level 3 Significant problems Worst case is 15 points and best case is 5 points using index</description>
          <population>One patient in the Active AlphaCore group is missing data at 8 weeks.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mobility-no problem baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mobility-no problem week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Self Care-no problem baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Self Care-no problem week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daily Activiies-no problem baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daily Activies- no problem week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain-no problem baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain-no problem week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety-no problem baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety-no problem week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With Adverse Events (AE)</title>
        <description>All AEs including but not limited to events reported by the subject or reported in response to an open question by the Clinical Investigator or member of this team, which fall into any of the above definitions must be recorded as an AE in the Case Report Form (CRF) and should include the following information.&#xD;
Brief description of the event (diagnosis)&#xD;
Start date (and time, if relevant)&#xD;
Stop date (and time, if relevant) (or resolution)&#xD;
Severity&#xD;
Action taken regarding the medical device&#xD;
Opinion on causality&#xD;
Seriousness&#xD;
Outcome</description>
        <time_frame>Throughout the course of the study (baseline to the 4 month follow-up visit)</time_frame>
        <population>All subjects reporting any Adverse Event</population>
        <group_list>
          <group group_id="O1">
            <title>Active AlphaCore Device</title>
            <description>Active AlphaCore Device&#xD;
Each study group will go under the same treatment regimen and assessments.</description>
          </group>
          <group group_id="O2">
            <title>Sham AlphaCore Device</title>
            <description>Sham AlphaCore Device&#xD;
Each study group will go under the same treatment regimen and assessments.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Adverse Events (AE)</title>
          <description>All AEs including but not limited to events reported by the subject or reported in response to an open question by the Clinical Investigator or member of this team, which fall into any of the above definitions must be recorded as an AE in the Case Report Form (CRF) and should include the following information.&#xD;
Brief description of the event (diagnosis)&#xD;
Start date (and time, if relevant)&#xD;
Stop date (and time, if relevant) (or resolution)&#xD;
Severity&#xD;
Action taken regarding the medical device&#xD;
Opinion on causality&#xD;
Seriousness&#xD;
Outcome</description>
          <population>All subjects reporting any Adverse Event</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Change in EuroQol, 5 Questions and 3 Levels (EQ-5D-3L), Visual Analogue Scale (VAS)</title>
        <description>Visual analogue scale (VAS) 0-100 where 0 is the worst imaginable health state and 100 the best imaginable health state</description>
        <time_frame>Baseline vs 8 weeks</time_frame>
        <population>One patient in the Active AlphaCore group missing data at 8 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Active AlphaCore Device</title>
            <description>Active AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
          <group group_id="O2">
            <title>Sham AlphaCore Device</title>
            <description>Sham AlphaCore Device Each study group will go under the same treatment regimen and assessments.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Change in EuroQol, 5 Questions and 3 Levels (EQ-5D-3L), Visual Analogue Scale (VAS)</title>
          <description>Visual analogue scale (VAS) 0-100 where 0 is the worst imaginable health state and 100 the best imaginable health state</description>
          <population>One patient in the Active AlphaCore group missing data at 8 weeks.</population>
          <units>units 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="25"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.3" spread="20.0"/>
                    <measurement group_id="O2" value="51.6" spread="16.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.8" spread="18.3"/>
                    <measurement group_id="O2" value="55.7" spread="20.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>16 weeks</time_frame>
      <desc>The first 8 weeks randomized controlled, the last 8 weeks open label</desc>
      <group_list>
        <group group_id="E1">
          <title>Active AlphaCore Device</title>
          <description>AlphaCore active stimulation treatment&#xD;
AlphaCore device: Each study group will go under the same treatment regimen and assessments.</description>
        </group>
        <group group_id="E2">
          <title>Sham AlphaCore Device</title>
          <description>AlphaCore sham device&#xD;
AlphaCore device: Each study group will go under the same treatment regimen and assessments.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>COPD exacerbation</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute COPD exacebartion</sub_title>
                <description>Hospitalized/Not related</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title vocab="Pulmonary embolism">Pulmonary embolism</sub_title>
                <description>Hospitalized/Not related</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title vocab="Bronchopneumonia">Bronchopneumonia both sides</sub_title>
                <description>Hospitalized/Not related</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title vocab="Cartoid stenosis">Cartoid stenosis left</sub_title>
                <description>Hospitalized/Not related</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="26"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>Common cold</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="4" subjects_at_risk="26"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Common cold</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title vocab="Respiratory infectio">Infection of the respiratory tract</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="26"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Annelie Andersson</name_or_title>
      <organization>electroCore LLC</organization>
      <phone>+46 721 803076</phone>
      <email>annelie.andersson@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/NCT01679314
org study id: AC-001
nct id: NCT01679314
lead sponsor: 
has dmc: Yes
The study will assess the treatment of patients with Chronic Obstructive Pulmonary Disease
      (COPD) stage III and IV who will self administer the AlphaCore stimulation three times a day
      over a course of 2 months. Patients will either receive an active AlphaCore device or a Sham
      device during these two months while not knowing which device they have been provided. At the
      end of the two months, all patients will be asked to continue in the study for another 2
      months to self administer with the active AlphaCore device. Subjects will complete diaries at
      home on their breathing and quality of life and will return to the clinic monthly for
      assessment by the investigator.
PERFORMANCE AND SAFETY VARIABLES:

      The primary efficacy endpoint for this study is the total Chronic obstructive pulmonary
      disease (COPD) Assessment Test (CAT) score change from baseline to the 8 week follow-up
      period comparing the two device groups.

      Secondary efficacy endpoints will be the mean difference from baseline to the 8 week
      follow-up for the following assessments: Medical Research Council (MRC) dyspnoea scale, 6
      minutes walking test and Forced Expiratory Volume in one second (FEV1)

      Safety Variables:

      Each subject will be assessed throughout the study for Adverse Events and at the last visit
      (4 months) subjects will undergo another physical examination including vital signs and blood
      pressure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores (Quality of Life and Symptoms) Changes Within a Treatment Period and Comparison Between the Two Groups
time frame: 8 weeks
description: Chronic obstructive pulmonary disease Assessment Test (CAT) scores (Quality of life and symptoms) changes within a treatment period and comparison between the two groups. Eight (8) questions. The scale is rated from 0 to 5, min = 0, max = 5. Low rates = better, high rates = worse. Mean change in the period 8 weeks versus baseline.
measure: Change in Borg Dyspnoea Scores
time frame: Baseline vs 8 weeks
description: Borg dyspnoea scale (Physical activity test): 0 - 11 (Not at all effected - Extremely effected) The result show the change between the the treatment groups from baseline to week 8
measure: Change 6 Minutes Walking Test
time frame: Baseline vs 8 weeks
description: Six minutes walking test: Measure distance (meter) after 6 minutes walk. Change from Baseline between treatment groups
measure: Change in Forced Expiratory Volume (FEV1)
time frame: Baseline vs 8 weeks
description: Forced Expiratory Volume (FEV1): Maximum volume that can be exhaled in the first second - after maximum inhalation.
Change from baseline to week 8 between treatment groups
measure: Change in EuroQol, 5 Questions and 3 Levels (EQ5D-3L)
time frame: Baseline vs 8 weeks
description: The EQ-5D-3L (EuroQoL 5 questions and 3 answering levels) during the run-in period will be compared with the EQ-5D-3L during the treatment period. And treatment period will be compared to open label.
Rating of questions Level 1 no problems Level 2 some problems Level 3 Significant problems Worst case is 15 points and best case is 5 points using index
measure: Number of Subjects With Adverse Events (AE)
time frame: Throughout the course of the study (baseline to the 4 month follow-up visit)
description: All AEs including but not limited to events reported by the subject or reported in response to an open question by the Clinical Investigator or member of this team, which fall into any of the above definitions must be recorded as an AE in the Case Report Form (CRF) and should include the following information.
Brief description of the event (diagnosis)
Start date (and time, if relevant)
Stop date (and time, if relevant) (or resolution)
Severity
Action taken regarding the medical device
Opinion on causality
Seriousness
Outcome
measure: Change in Change in EuroQol, 5 Questions and 3 Levels (EQ-5D-3L), Visual Analogue Scale (VAS)
time frame: Baseline vs 8 weeks
description: Visual analogue scale (VAS) 0-100 where 0 is the worst imaginable health state and 100 the best imaginable health state
arm group label: Active AlphaCore device
arm group type: Active Comparator
description: AlphaCore active stimulation treatment
arm group label: Sham AlphaCore device
arm group type: Sham Comparator
description: AlphaCore sham device
intervention type: Device
intervention name: AlphaCore device
description: Each study group will go under the same treatment regimen and assessments.
arm group label: Active AlphaCore device
arm group label: Sham AlphaCore device
criteria: 
gender: All
minimum age: 40 Years
maximum age: 75 Years
healthy volunteers: No
last name: Matthias John, MD
role: Principal Investigator
affiliation: Praxis für Pneumologie am Asklepios Klinikum Uckermark
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No
ipd description: No description
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 