<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/NCT02972047</url>
  </required_header>
  <id_info>
    <org_study_id>16-007005</org_study_id>
    <nct_id>NCT02972047</nct_id>
  </id_info>
  <brief_title>Understanding the Pathophysiology and Effects of Diaphragmatic Breathing in Upright Gastroesophageal Reflux</brief_title>
  <official_title>Understanding the Pathophysiology and Effects of Diaphragmatic Breathing in Upright Gastroesophageal Reflux</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</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 study aims to understand why patients have predominantly upright gastroesophageal reflux&#xD;
      disease by comparing such patients to healthy persons AND whether a behavioral intervention&#xD;
      (diaphragmatic breathing) will impact this disease&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are two major patterns of gastroesophageal reflux disease (GERD), predominantly daytime&#xD;
      and upright reflux and predominantly nocturnal and supine reflux.&#xD;
&#xD;
      Traditionally, upright reflux has been attributed to more frequent or wider opening with&#xD;
      transient lower esophageal sphincter relaxations (TLESRs) while supine reflux results from a&#xD;
      consistently reduced lower esophageal sphincter (LES) pressure. This may further be accounted&#xD;
      for by the finding of larger hiatal hernias and greater pressure gradients between the crura&#xD;
      and LES when comparing supine to upright refluxers. These findings may help explain supine&#xD;
      reflux, but they offer little insight into the mechanisms of upright reflux.&#xD;
&#xD;
      In this study the investigators will be recruiting twenty healthy persons and up to 60&#xD;
      patients with GERD will be recruited from the clinical practice at Mayo Clinic Rochester. The&#xD;
      investigators aim to study the intervention on 40 patients with GERD. However, recognizing&#xD;
      that up to 33% of patients with typical symptoms of GERD will not have reflux by ambulatory&#xD;
      pH monitoring (pH power of hydration), the investigators provide for enrolling up to a&#xD;
      maximum of 60 patients which should be sufficient to yield 40 patients with upright GERD by&#xD;
      pH monitoring. In addition, up to 10 additional healthy persons may be recruited.&#xD;
&#xD;
      Subjects with upright reflux and healthy controls will be randomized into one of two groups:&#xD;
&#xD;
      Experimental: Diaphragmatic breathing or Sham comparator: (listening to music/watching&#xD;
      Television (TV) for 30 minutes after each meal to see how this impacts the disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 6, 2017</start_date>
  <completion_date type="Actual">August 30, 2020</completion_date>
  <primary_completion_date type="Actual">August 1, 2020</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>The total esophageal acid exposure time during the diagnostic 24hour pH study compared with the interventional study</measure>
    <time_frame>2 days</time_frame>
    <description>The investigators will compare the total esophageal acid exposure time in minutes during the first 24 hour ambulatory pH study with the second 24 period during which patients are either randomized to biofeedback versus sham</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Upper gastrointestinal pressures in patients with upright GER compared to healthy people</measure>
    <time_frame>2 days</time_frame>
    <description>Upper gastrointestinal pressures and pressure changes associated with meals will be described. Pressure differences will be measured in mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of provocative maneuvers on upper gastrointestinal pressures.</measure>
    <time_frame>2 days</time_frame>
    <description>The investigators will compare the effects of provocative maneuvers on upper gastrointestinal pressure. Pressure differences will be measured in mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of provocative maneuvers on reflux</measure>
    <time_frame>2 days</time_frame>
    <description>The investigators will compare the effects of provocative maneuvers on reflux as measured with impedance (Ohms)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effects of diaphragmatic breathing on upper gastrointestinal pressures</measure>
    <time_frame>2 days</time_frame>
    <description>The investigators will report any pressure changes (measures in mmHg) associated with diaphragmatic breathing on upper gastrointestinal pressure.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>GERD</condition>
  <arm_group>
    <arm_group_label>Diaphragmatic Breathing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects randomized to the experimental intervention arm will receive instructions and rationale for Diaphragmatic Breathing in the postprandial state and receive detailed instruction in diaphragmatic breathing.&#xD;
Following the office visit the patients with upright GERD and healthy persons will undergo a further 24 hours of pH impedance monitoring. This group will practice diaphragmatic breathing for 30 minutes after each meal.&#xD;
During the second 24 hour period patients with GERD and healthy persons will again consume the standard pH neutral refluxogenic meal note this with an event marker&#xD;
After 48 hours patients with GERD and healthy persons will present to the esophageal laboratory for probe removal</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Life style counseling</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Subjects randomized to the Sham Comparator intervention arm will engage in sham therapy (listening to music/watching TV for 30 minutes after each meal)&#xD;
Following the office visit the patients with upright GERD and healthy persons will undergo a further 24 hours of pH impedance monitoring. This group will will engage in sham therapy (listening to music/watching TV for 30 minutes after each meal)&#xD;
During the second 24 hour period patients with GERD and healthy persons will again consume the standard pH neutral refluxogenic meal note this with an event marker&#xD;
After 48 hours patients with GERD and healthy persons will present to the esophageal laboratory for probe removal</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Diaphragmatic Breathing</intervention_name>
    <description>Subjects in this are practice diaphragmatic breathing for 30 minutes after each meal.</description>
    <arm_group_label>Diaphragmatic Breathing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Sham Comparator</intervention_name>
    <description>Sham therapy (listening to music/watching TV for 30 minutes after each meal</description>
    <arm_group_label>Life style counseling</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for Healthy Persons:&#xD;
&#xD;
        -Patients 18 years of age or older with no symptoms of GERD&#xD;
&#xD;
        Inclusion Criteria for Patients:&#xD;
&#xD;
          -  Patients 18 years of age or older with symptoms of GERD&#xD;
&#xD;
          -  Upper gastrointestinal endoscopy within the past 6 months and a prior diagnostic pH&#xD;
             impedance study showing predominantly upright reflux&#xD;
&#xD;
        Exclusion Criteria for Patients; Items indicated with an asterisk (*) are also exclusion&#xD;
        criteria for healthy persons&#xD;
&#xD;
          -  Patient who fulfil ROME IV Criteria for rumination disorder20&#xD;
&#xD;
          -  Clinical evidence of significant cardiovascular, respiratory, renal, hepatic,&#xD;
             gastrointestinal, hematological, neurological (e.g., spinal cord injuries, dementia,&#xD;
             multiple sclerosis, Parkinson's disease), psychiatric or other disease that may&#xD;
             interfere with the objectives of the study and/or pose safety concerns.*&#xD;
&#xD;
          -  Any prior gastric or esophageal surgery and significant intestinal or colonic&#xD;
             resection*&#xD;
&#xD;
          -  Hiatal hernia measuring 3 cm or larger as assessed by endoscopic or radiological&#xD;
             studies&#xD;
&#xD;
          -  Prior history of Los Angeles Grade C or D esophagitis, or esophageal stricture.&#xD;
&#xD;
          -  Current use opioid analgesics or anticholinergic drugs.* We will permit low doses of&#xD;
             tricyclic antidepressants, nortriptyline (up to 50 mg/day) or amitriptyline (up to 25&#xD;
             mg/day) provided they were commenced 3 months prior to the screening period, calcium&#xD;
             channel or adrenergic1 antagonists&#xD;
&#xD;
          -  Current use of proton pump inhibitors&#xD;
&#xD;
          -  Known significant esophageal motor disorder (ie achalasia, aperistalsis, functional&#xD;
             obstruction, jackhammer, distal esophageal spasm)*&#xD;
&#xD;
          -  Inability to read due to: blindness, cognitive dysfunction, or English language&#xD;
             illiteracy *&#xD;
&#xD;
          -  Pregnant and lactating females *&#xD;
&#xD;
        Exclusion Criteria for Healthy Persons in addition to those marked with an Asterisk (*)&#xD;
        above&#xD;
&#xD;
          -  Ongoing use of Proton Pump Inhibitors ( PPIs) or a history consistent with GE reflux&#xD;
             for 3 months or longer duration in past.&#xD;
&#xD;
          -  Prior history of Los Angeles Grade B-D esophagitis&#xD;
&#xD;
          -  Prior history of GERD on the basis of pH testing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Magnus Halland, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>December 2, 2020</last_update_submitted>
  <last_update_submitted_qc>December 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Magnus Halland</investigator_full_name>
    <investigator_title>PI</investigator_title>
  </responsible_party>
  <keyword>Reflux</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>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02972047
org study id: 16-007005
nct id: NCT02972047
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to understand why patients have predominantly upright gastroesophageal reflux
      disease by comparing such patients to healthy persons AND whether a behavioral intervention
      (diaphragmatic breathing) will impact this disease
There are two major patterns of gastroesophageal reflux disease (GERD), predominantly daytime
      and upright reflux and predominantly nocturnal and supine reflux.

      Traditionally, upright reflux has been attributed to more frequent or wider opening with
      transient lower esophageal sphincter relaxations (TLESRs) while supine reflux results from a
      consistently reduced lower esophageal sphincter (LES) pressure. This may further be accounted
      for by the finding of larger hiatal hernias and greater pressure gradients between the crura
      and LES when comparing supine to upright refluxers. These findings may help explain supine
      reflux, but they offer little insight into the mechanisms of upright reflux.

      In this study the investigators will be recruiting twenty healthy persons and up to 60
      patients with GERD will be recruited from the clinical practice at Mayo Clinic Rochester. The
      investigators aim to study the intervention on 40 patients with GERD. However, recognizing
      that up to 33% of patients with typical symptoms of GERD will not have reflux by ambulatory
      pH monitoring (pH power of hydration), the investigators provide for enrolling up to a
      maximum of 60 patients which should be sufficient to yield 40 patients with upright GERD by
      pH monitoring. In addition, up to 10 additional healthy persons may be recruited.

      Subjects with upright reflux and healthy controls will be randomized into one of two groups:

      Experimental: Diaphragmatic breathing or Sham comparator: (listening to music/watching
      Television (TV) for 30 minutes after each meal to see how this impacts the disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: The total esophageal acid exposure time during the diagnostic 24hour pH study compared with the interventional study
time frame: 2 days
description: The investigators will compare the total esophageal acid exposure time in minutes during the first 24 hour ambulatory pH study with the second 24 period during which patients are either randomized to biofeedback versus sham
measure: Upper gastrointestinal pressures in patients with upright GER compared to healthy people
time frame: 2 days
description: Upper gastrointestinal pressures and pressure changes associated with meals will be described. Pressure differences will be measured in mmHg.
measure: The effects of provocative maneuvers on upper gastrointestinal pressures.
time frame: 2 days
description: The investigators will compare the effects of provocative maneuvers on upper gastrointestinal pressure. Pressure differences will be measured in mmHg.
measure: The effects of provocative maneuvers on reflux
time frame: 2 days
description: The investigators will compare the effects of provocative maneuvers on reflux as measured with impedance (Ohms)
measure: The effects of diaphragmatic breathing on upper gastrointestinal pressures
time frame: 2 days
description: The investigators will report any pressure changes (measures in mmHg) associated with diaphragmatic breathing on upper gastrointestinal pressure.
arm group label: Diaphragmatic Breathing
arm group type: Experimental
description: Subjects randomized to the experimental intervention arm will receive instructions and rationale for Diaphragmatic Breathing in the postprandial state and receive detailed instruction in diaphragmatic breathing.
Following the office visit the patients with upright GERD and healthy persons will undergo a further 24 hours of pH impedance monitoring. This group will practice diaphragmatic breathing for 30 minutes after each meal.
During the second 24 hour period patients with GERD and healthy persons will again consume the standard pH neutral refluxogenic meal note this with an event marker
After 48 hours patients with GERD and healthy persons will present to the esophageal laboratory for probe removal
arm group label: Life style counseling
arm group type: Sham Comparator
description: Subjects randomized to the Sham Comparator intervention arm will engage in sham therapy (listening to music/watching TV for 30 minutes after each meal)
Following the office visit the patients with upright GERD and healthy persons will undergo a further 24 hours of pH impedance monitoring. This group will will engage in sham therapy (listening to music/watching TV for 30 minutes after each meal)
During the second 24 hour period patients with GERD and healthy persons will again consume the standard pH neutral refluxogenic meal note this with an event marker
After 48 hours patients with GERD and healthy persons will present to the esophageal laboratory for probe removal
intervention type: Behavioral
intervention name: Diaphragmatic Breathing
description: Subjects in this are practice diaphragmatic breathing for 30 minutes after each meal.
arm group label: Diaphragmatic Breathing
intervention type: Behavioral
intervention name: Sham Comparator
description: Sham therapy (listening to music/watching TV for 30 minutes after each meal
arm group label: Life style counseling
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Magnus Halland, MD
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Magnus Halland
investigator title: PI
mesh term: Gastroesophageal Reflux
sharing ipd: No