<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/NCT03020550</url>
  </required_header>
  <id_info>
    <org_study_id>2016P001628</org_study_id>
    <secondary_id>1K23AT009218</secondary_id>
    <nct_id>NCT03020550</nct_id>
  </id_info>
  <brief_title>Correlates of GERD Symptom Severity</brief_title>
  <official_title>Physiologic and Behavioral Correlates of GERD Symptom Severity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center for Complementary and Integrative Health (NCCIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study measuring physiologic and behavioral correlates of symptom severity in&#xD;
      adult patients with gastroesophageal reflux disease (GERD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will complete questionnaires regarding their GERD-related symptoms and have a visit&#xD;
      with a study clinician regarding their symptoms. We will measure heart rate variability and&#xD;
      galvanic skin response in patients during the visits and video record the visits. Subjects&#xD;
      will complete a daily GERD symptom diary for 2 weeks and then return to the study center to&#xD;
      complete additional questionnaires and an exit interview.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 22, 2017</start_date>
  <completion_date type="Actual">May 7, 2019</completion_date>
  <primary_completion_date type="Actual">May 3, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Association of Change in Patient's GSR From Beginning to End of Study Visit With GERD Symptom Severity 2 Weeks Later</measure>
    <time_frame>Beginning to end of study visit (1 hour or less for change in GSR)</time_frame>
    <description>Galvanic skin response (GSR) was measured with a device from ADInstruments during the baseline study visit. Values ranged from 0.93 - 12 micro-Siemens (μS). Change in GSR was calculated as mean value of GSR for the first 2 minutes of the study visit minus mean value of GSR for the last 2 minutes of the study visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Association of Change in Patient's High Frequency HRV From Beginning to End of Study Visit With GERD Symptom Severity 2 Weeks Later</measure>
    <time_frame>Beginning to end of study visit (1 hour or less for change in HRV/RMSSD)</time_frame>
    <description>Heart rate variability (HRV) was measured using a device from ADInstruments gathering data at 256 Hz. We used the RMSSD (Root Mean Square of the Successive Differences) value as a proxy for high frequency HRV. Measured values ranged from 0 - 150 msec. Change in high frequency HRV was calculated as the RMSSD value for the first 5 minutes of the study visit minus the RMSSD value for the last 5 minutes of the study visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation Between Concordance in GSR Between Patient and Physician During the Study Visit and Percent Change in Patients' GERD Symptoms Over 2 Weeks</measure>
    <time_frame>Beginning to end of study visit (1 hour or less for concordance between patient and physician GSR)</time_frame>
    <description>Concordance in galvanic skin response (GSR) between patient and physician was calculated using an established approach (Marci CD, 2007; PMID 17299296) to create a single index value for the visit. The natural logarithm of this value was taken to reduce skew. A value greater than 0 means more than 50% concordance in the data, a value less than zero means less than 50% concordance in the data.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Post GERD Symptom Severity</measure>
    <time_frame>2 weeks (baseline and 2 week follow-up)</time_frame>
    <description>GERD symptom severity at follow-up was assessed by self-report on a 7-day symptom diary (symptoms collected days 8-14 after the study visit). Possible daily scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation symptoms each rated 0-4 in severity [none, mild, moderate, severe, very severe]). Daily scores across the 7 days were averaged to create the Post GERD symptom severity score. Adapted from: Miner P, et. al. Am J Gastroenterol. 2002. PMID: 12094846.</description>
  </other_outcome>
  <other_outcome>
    <measure>Percent Change in Patient's GERD Symptoms</measure>
    <time_frame>2 weeks (baseline and 2 week follow-up)</time_frame>
    <description>Percent change in patient's GERD symptoms was calculated as: (post GERD symptom severity - baseline GERD symptom severity) / baseline GERD symptom severity*100.&#xD;
GERD symptom severity scores were averaged across 7 day baseline and follow-up periods from a symptom diary (adapted from Miner P, 2002; PMID 12094846). Scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation each rated 0-4 in severity [none, mild, moderate, severe, very severe]).</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">24</enrollment>
  <condition>GERD</condition>
  <arm_group>
    <arm_group_label>GERD Patients</arm_group_label>
    <description>Subjects with active GERD symptoms.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Adults with active GERD-related symptoms.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults ages 21-70 years old&#xD;
&#xD;
          -  Heartburn symptoms 3 or more days per week with an average daily symptom severity of 3&#xD;
             or more on a 7 day baseline symptom diary&#xD;
&#xD;
          -  English language proficiency&#xD;
&#xD;
          -  Willingness to be videotaped and connected to physiologic monitoring devices during&#xD;
             the visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Crohn's disease, systemic sclerosis, known active ulcer disease, gastric&#xD;
             cancer, or untreated/active Barrett's esophagitis based on subject self-report and/or&#xD;
             medical record review&#xD;
&#xD;
          -  Heavy alcohol use (&gt; 6 drinks/week for women and &gt; 13 drinks/week for men)&#xD;
&#xD;
          -  Pregnant women.&#xD;
&#xD;
          -  Dementia or significant memory difficulties&#xD;
&#xD;
          -  Severe, unstable psychiatric disease&#xD;
&#xD;
          -  Greater than 15 doses of nonsteroidal anti-inflammatory drugs (NSAIDS) within the&#xD;
             prior 30 days (aspirin ≤ 325 mg daily permitted) or ongoing NSAID use at a level&#xD;
             deemed likely to interfere with the study&#xD;
&#xD;
          -  Failure to complete the baseline symptom diary for at least 6 of 7 days&#xD;
&#xD;
          -  Change in GERD treatment regimen within the last 2 weeks (subjects may use antacids,&#xD;
             H2 receptor blockers, and/or proton pump inhibitors as long as they are symptomatic on&#xD;
             a stable regimen)&#xD;
&#xD;
          -  Allergy to adhesives&#xD;
&#xD;
          -  Inability to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michelle Dossett, MD, PHD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>August 27, 2020</results_first_submitted>
  <results_first_submitted_qc>December 22, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 15, 2021</results_first_posted>
  <last_update_submitted>December 22, 2020</last_update_submitted>
  <last_update_submitted_qc>December 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Michelle Dossett, MD, PhD, MPH</investigator_full_name>
    <investigator_title>Assistant Physician</investigator_title>
  </responsible_party>
  <keyword>GERD</keyword>
  <keyword>Galvanic Skin Response</keyword>
  <keyword>Heart Rate Variability</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroesophageal Reflux</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 8, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03020550/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Standard Visit</title>
          <description>A standardized visit (based on a pre-set question template) modeled after a primary care visit focused on evaluating GERD symptoms.</description>
        </group>
        <group group_id="P2">
          <title>Expanded Visit</title>
          <description>A standardized visit (based on a pre-set question template) modeled after an integrative medicine visit for GERD symptoms. The Expanded Visit includes all of the questions in the Standard Visit plus additional questions about the nature of the GI symptoms (e.g., taste of reflux, food cravings and aversions), other health issues, and the patient's temperament (e.g., shy, anxious, caring). Some of these questions address the patient's &quot;constitutional type&quot; as might be assessed by some integrative practitioners (e.g., tell me about your sleep; do you tend to be hot or cold?).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Standard Visit</title>
          <description>Patients with GERD receiving a standard medical visit</description>
        </group>
        <group group_id="B2">
          <title>Expanded Visit</title>
          <description>Patients with GERD receiving an expanded medical visit modeled after an integrative medicine consultation</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="8"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="24"/>
          </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="37.5" spread="15.7"/>
                    <measurement group_id="B2" value="41.1" spread="16.7"/>
                    <measurement group_id="B3" value="39.9" spread="16.1"/>
                  </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="5"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Average Daily GERD Symptom Severity</title>
          <description>Severity of GERD symptoms were assessed by participant self-report on a 7-day symptom diary for one week immediately prior to enrolling in the study. Possible daily scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation symptoms each rated 0-4 in severity [none, mild, moderate, severe, very severe]). Daily values across each of the 7 days were averaged to create the average daily GERD symptom severity score. Adapted from: Miner P, et. al. Am J Gastroenterol. 2002 Jun;97(6):1332-1339. PMID: 12094846</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.90" spread="1.7"/>
                    <measurement group_id="B2" value="2.95" spread="1.2"/>
                    <measurement group_id="B3" value="3.26" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Association of Change in Patient's GSR From Beginning to End of Study Visit With GERD Symptom Severity 2 Weeks Later</title>
        <description>Galvanic skin response (GSR) was measured with a device from ADInstruments during the baseline study visit. Values ranged from 0.93 - 12 micro-Siemens (μS). Change in GSR was calculated as mean value of GSR for the first 2 minutes of the study visit minus mean value of GSR for the last 2 minutes of the study visit.</description>
        <time_frame>Beginning to end of study visit (1 hour or less for change in GSR)</time_frame>
        <population>Intent to treat analysis. Subjects with missing GSR data (due to equipment malfunction) were not included in the final analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Visit</title>
            <description>Patients with GERD receiving a standard medical visit</description>
          </group>
          <group group_id="O2">
            <title>Expanded Visit</title>
            <description>Patients with GERD receiving an expanded medical visit modeled after an integrative medicine consultation</description>
          </group>
        </group_list>
        <measure>
          <title>Association of Change in Patient's GSR From Beginning to End of Study Visit With GERD Symptom Severity 2 Weeks Later</title>
          <description>Galvanic skin response (GSR) was measured with a device from ADInstruments during the baseline study visit. Values ranged from 0.93 - 12 micro-Siemens (μS). Change in GSR was calculated as mean value of GSR for the first 2 minutes of the study visit minus mean value of GSR for the last 2 minutes of the study visit.</description>
          <population>Intent to treat analysis. Subjects with missing GSR data (due to equipment malfunction) were not included in the final analysis.</population>
          <units>micro-Siemens</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.94" spread="1.3"/>
                    <measurement group_id="O2" value="-1.70" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The outcome measure was calculated using a general linear model with average daily post GERD symptom severity as the dependent variable with the following independent variables: baseline average GERD symptom severity and change in GSR (galvanic skin response). No term for visit type assignment was included in the model.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.034</p_value>
            <method>ANOVA</method>
            <method_desc>Adjusted for baseline GERD symptom severity.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Association of Change in Patient's High Frequency HRV From Beginning to End of Study Visit With GERD Symptom Severity 2 Weeks Later</title>
        <description>Heart rate variability (HRV) was measured using a device from ADInstruments gathering data at 256 Hz. We used the RMSSD (Root Mean Square of the Successive Differences) value as a proxy for high frequency HRV. Measured values ranged from 0 - 150 msec. Change in high frequency HRV was calculated as the RMSSD value for the first 5 minutes of the study visit minus the RMSSD value for the last 5 minutes of the study visit.</description>
        <time_frame>Beginning to end of study visit (1 hour or less for change in HRV/RMSSD)</time_frame>
        <population>Intent to treat analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Visit</title>
            <description>Patients with GERD receiving a standard medical visit</description>
          </group>
          <group group_id="O2">
            <title>Expanded Visit</title>
            <description>Patients with GERD receiving an expanded medical visit modeled after an integrative medicine consultation</description>
          </group>
        </group_list>
        <measure>
          <title>Association of Change in Patient's High Frequency HRV From Beginning to End of Study Visit With GERD Symptom Severity 2 Weeks Later</title>
          <description>Heart rate variability (HRV) was measured using a device from ADInstruments gathering data at 256 Hz. We used the RMSSD (Root Mean Square of the Successive Differences) value as a proxy for high frequency HRV. Measured values ranged from 0 - 150 msec. Change in high frequency HRV was calculated as the RMSSD value for the first 5 minutes of the study visit minus the RMSSD value for the last 5 minutes of the study visit.</description>
          <population>Intent to treat analysis.</population>
          <units>milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.26" spread="8.3"/>
                    <measurement group_id="O2" value="2.5" spread="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The outcome measure was calculated using a general linear model with average daily post GERD symptom severity as the dependent variable with the following independent variables: baseline average GERD symptom severity and change in RMSSD (high frequency HRV). No term for visit type assignment was included in the model.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.56</p_value>
            <method>ANOVA</method>
            <method_desc>Adjusted for baseline GERD symptom severity</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Correlation Between Concordance in GSR Between Patient and Physician During the Study Visit and Percent Change in Patients' GERD Symptoms Over 2 Weeks</title>
        <description>Concordance in galvanic skin response (GSR) between patient and physician was calculated using an established approach (Marci CD, 2007; PMID 17299296) to create a single index value for the visit. The natural logarithm of this value was taken to reduce skew. A value greater than 0 means more than 50% concordance in the data, a value less than zero means less than 50% concordance in the data.</description>
        <time_frame>Beginning to end of study visit (1 hour or less for concordance between patient and physician GSR)</time_frame>
        <population>Intent to treat. Subjects with missing GSR data (due to equipment malfunction) were not included in the final analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Visit</title>
            <description>Patients with GERD receiving a standard medical visit</description>
          </group>
          <group group_id="O2">
            <title>Expanded Visit</title>
            <description>Patients with GERD receiving an expanded medical visit modeled after an integrative medicine consultation</description>
          </group>
        </group_list>
        <measure>
          <title>Correlation Between Concordance in GSR Between Patient and Physician During the Study Visit and Percent Change in Patients' GERD Symptoms Over 2 Weeks</title>
          <description>Concordance in galvanic skin response (GSR) between patient and physician was calculated using an established approach (Marci CD, 2007; PMID 17299296) to create a single index value for the visit. The natural logarithm of this value was taken to reduce skew. A value greater than 0 means more than 50% concordance in the data, a value less than zero means less than 50% concordance in the data.</description>
          <population>Intent to treat. Subjects with missing GSR data (due to equipment malfunction) were not included in the final analysis.</population>
          <units>Index</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.0536" spread="0.19"/>
                    <measurement group_id="O2" value="0.199" spread="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The outcome measure was calculated using a Pearson correlation to compare the session index representing the amount of concordance in GSR between patient and physician and the percent change in patients' GERD symptoms. Visit type assignment was not included in the analysis.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.80</p_value>
            <method>Pearson's correlation test</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Post GERD Symptom Severity</title>
        <description>GERD symptom severity at follow-up was assessed by self-report on a 7-day symptom diary (symptoms collected days 8-14 after the study visit). Possible daily scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation symptoms each rated 0-4 in severity [none, mild, moderate, severe, very severe]). Daily scores across the 7 days were averaged to create the Post GERD symptom severity score. Adapted from: Miner P, et. al. Am J Gastroenterol. 2002. PMID: 12094846.</description>
        <time_frame>2 weeks (baseline and 2 week follow-up)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Standard Visit</title>
            <description>Patients with GERD receiving a standard medical visit</description>
          </group>
          <group group_id="O2">
            <title>Expanded Visit</title>
            <description>Patients with GERD receiving an expanded medical visit modeled after an integrative medicine consultation</description>
          </group>
        </group_list>
        <measure>
          <title>Post GERD Symptom Severity</title>
          <description>GERD symptom severity at follow-up was assessed by self-report on a 7-day symptom diary (symptoms collected days 8-14 after the study visit). Possible daily scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation symptoms each rated 0-4 in severity [none, mild, moderate, severe, very severe]). Daily scores across the 7 days were averaged to create the Post GERD symptom severity score. Adapted from: Miner P, et. al. Am J Gastroenterol. 2002. PMID: 12094846.</description>
          <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="8"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.77" spread="1.48"/>
                    <measurement group_id="O2" value="2.41" spread="1.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Percent Change in Patient's GERD Symptoms</title>
        <description>Percent change in patient's GERD symptoms was calculated as: (post GERD symptom severity - baseline GERD symptom severity) / baseline GERD symptom severity*100.&#xD;
GERD symptom severity scores were averaged across 7 day baseline and follow-up periods from a symptom diary (adapted from Miner P, 2002; PMID 12094846). Scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation each rated 0-4 in severity [none, mild, moderate, severe, very severe]).</description>
        <time_frame>2 weeks (baseline and 2 week follow-up)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Standard Visit</title>
            <description>Patients with GERD receiving a standard medical visit</description>
          </group>
          <group group_id="O2">
            <title>Expanded Visit</title>
            <description>Patients with GERD receiving an expanded medical visit modeled after an integrative medicine consultation</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Patient's GERD Symptoms</title>
          <description>Percent change in patient's GERD symptoms was calculated as: (post GERD symptom severity - baseline GERD symptom severity) / baseline GERD symptom severity*100.&#xD;
GERD symptom severity scores were averaged across 7 day baseline and follow-up periods from a symptom diary (adapted from Miner P, 2002; PMID 12094846). Scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation each rated 0-4 in severity [none, mild, moderate, severe, very severe]).</description>
          <units>Percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3" spread="45"/>
                    <measurement group_id="O2" value="-12.2" spread="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Standard Visit</title>
          <description>Patients with GERD receiving a standard medical visit</description>
        </group>
        <group group_id="E2">
          <title>Expanded Visit</title>
          <description>Patients with GERD receiving an expanded medical visit modeled after an integrative medicine consultation</description>
        </group>
      </group_list>
      <serious_events>
        <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="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <description>1 subject developed gastroenteritis and presented to the emergency department where they received IV fluids. Adverse event deemed not related to the study intervention.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
              </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>
    <limitations_and_caveats>Equipment malfunction led to incomplete data collection for some subjects, reducing the total number of subjects in some of the data analyses.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Michelle Dossett, MD, PhD</name_or_title>
      <organization>University of California, Davis</organization>
      <phone>916-734-5367</phone>
      <email>mdossett@ucdavis.edu</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/NCT03020550
org study id: 2016P001628
secondary id: 1K23AT009218
nct id: NCT03020550
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a pilot study measuring physiologic and behavioral correlates of symptom severity in
      adult patients with gastroesophageal reflux disease (GERD).
Subjects will complete questionnaires regarding their GERD-related symptoms and have a visit
      with a study clinician regarding their symptoms. We will measure heart rate variability and
      galvanic skin response in patients during the visits and video record the visits. Subjects
      will complete a daily GERD symptom diary for 2 weeks and then return to the study center to
      complete additional questionnaires and an exit interview.
observational model: Cohort
time perspective: Prospective
measure: Association of Change in Patient's GSR From Beginning to End of Study Visit With GERD Symptom Severity 2 Weeks Later
time frame: Beginning to end of study visit (1 hour or less for change in GSR)
description: Galvanic skin response (GSR) was measured with a device from ADInstruments during the baseline study visit. Values ranged from 0.93 - 12 micro-Siemens (μS). Change in GSR was calculated as mean value of GSR for the first 2 minutes of the study visit minus mean value of GSR for the last 2 minutes of the study visit.
measure: Association of Change in Patient's High Frequency HRV From Beginning to End of Study Visit With GERD Symptom Severity 2 Weeks Later
time frame: Beginning to end of study visit (1 hour or less for change in HRV/RMSSD)
description: Heart rate variability (HRV) was measured using a device from ADInstruments gathering data at 256 Hz. We used the RMSSD (Root Mean Square of the Successive Differences) value as a proxy for high frequency HRV. Measured values ranged from 0 - 150 msec. Change in high frequency HRV was calculated as the RMSSD value for the first 5 minutes of the study visit minus the RMSSD value for the last 5 minutes of the study visit.
measure: Correlation Between Concordance in GSR Between Patient and Physician During the Study Visit and Percent Change in Patients' GERD Symptoms Over 2 Weeks
time frame: Beginning to end of study visit (1 hour or less for concordance between patient and physician GSR)
description: Concordance in galvanic skin response (GSR) between patient and physician was calculated using an established approach (Marci CD, 2007; PMID 17299296) to create a single index value for the visit. The natural logarithm of this value was taken to reduce skew. A value greater than 0 means more than 50% concordance in the data, a value less than zero means less than 50% concordance in the data.
measure: Post GERD Symptom Severity
time frame: 2 weeks (baseline and 2 week follow-up)
description: GERD symptom severity at follow-up was assessed by self-report on a 7-day symptom diary (symptoms collected days 8-14 after the study visit). Possible daily scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation symptoms each rated 0-4 in severity [none, mild, moderate, severe, very severe]). Daily scores across the 7 days were averaged to create the Post GERD symptom severity score. Adapted from: Miner P, et. al. Am J Gastroenterol. 2002. PMID: 12094846.
measure: Percent Change in Patient's GERD Symptoms
time frame: 2 weeks (baseline and 2 week follow-up)
description: Percent change in patient's GERD symptoms was calculated as: (post GERD symptom severity - baseline GERD symptom severity) / baseline GERD symptom severity*100.
GERD symptom severity scores were averaged across 7 day baseline and follow-up periods from a symptom diary (adapted from Miner P, 2002; PMID 12094846). Scores ranged from 0-12 with higher scores indicating more severe symptoms (sum of daytime heartburn, nighttime heartburn, and acid regurgitation each rated 0-4 in severity [none, mild, moderate, severe, very severe]).
arm group label: GERD Patients
description: Subjects with active GERD symptoms.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: No
last name: Michelle Dossett, MD, PHD, MPH
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Michelle Dossett, MD, PhD, MPH
investigator title: Assistant Physician
mesh term: Gastroesophageal Reflux
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Equipment malfunction led to incomplete data collection for some subjects, reducing the total number of subjects in some of the data analyses.
point of contact: 