Understanding the Pathophysiology and Effects of Diaphragmatic Breathing in Upright Gastroesophageal Reflux

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

Study Overview

• Status: Completed
• Conditions: GERD
• Intervention / Treatment: Behavioral: Diaphragmatic Breathing; Behavioral: Sham Comparator

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for Healthy Persons:

-Patients 18 years of age or older with no symptoms of GERD

Inclusion Criteria for Patients:

• Patients 18 years of age or older with symptoms of GERD
• Upper gastrointestinal endoscopy within the past 6 months and a prior diagnostic pH impedance study showing predominantly upright reflux

Exclusion Criteria for Patients; Items indicated with an asterisk (*) are also exclusion criteria for healthy persons

• Patient who fulfil ROME IV Criteria for rumination disorder20
• Clinical evidence of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological (e.g., spinal cord injuries, dementia, multiple sclerosis, Parkinson's disease), psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns.*
• Any prior gastric or esophageal surgery and significant intestinal or colonic resection*
• Hiatal hernia measuring 3 cm or larger as assessed by endoscopic or radiological studies
• Prior history of Los Angeles Grade C or D esophagitis, or esophageal stricture.
• Current use opioid analgesics or anticholinergic drugs.* We will permit low doses of tricyclic antidepressants, nortriptyline (up to 50 mg/day) or amitriptyline (up to 25 mg/day) provided they were commenced 3 months prior to the screening period, calcium channel or adrenergic1 antagonists
• Current use of proton pump inhibitors
• Known significant esophageal motor disorder (ie achalasia, aperistalsis, functional obstruction, jackhammer, distal esophageal spasm)*
• Inability to read due to: blindness, cognitive dysfunction, or English language illiteracy *
• Pregnant and lactating females *

Exclusion Criteria for Healthy Persons in addition to those marked with an Asterisk (*) above

• Ongoing use of Proton Pump Inhibitors ( PPIs) or a history consistent with GE reflux for 3 months or longer duration in past.
• Prior history of Los Angeles Grade B-D esophagitis
• Prior history of GERD on the basis of pH testing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Diaphragmatic Breathing; 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	Behavioral: Diaphragmatic Breathing; Subjects in this are practice diaphragmatic breathing for 30 minutes after each meal.
SHAM_COMPARATOR: Life style counseling; 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	Behavioral: Sham Comparator; Sham therapy (listening to music/watching TV for 30 minutes after each meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total esophageal acid exposure time during the diagnostic 24hour pH study compared with the interventional study	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	2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper gastrointestinal pressures in patients with upright GER compared to healthy people	Upper gastrointestinal pressures and pressure changes associated with meals will be described. Pressure differences will be measured in mmHg.	2 days
The effects of provocative maneuvers on upper gastrointestinal pressures.	The investigators will compare the effects of provocative maneuvers on upper gastrointestinal pressure. Pressure differences will be measured in mmHg.	2 days
The effects of provocative maneuvers on reflux	The investigators will compare the effects of provocative maneuvers on reflux as measured with impedance (Ohms)	2 days
The effects of diaphragmatic breathing on upper gastrointestinal pressures	The investigators will report any pressure changes (measures in mmHg) associated with diaphragmatic breathing on upper gastrointestinal pressure.	2 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Magnus Halland, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 6, 2017
• Primary Completion (ACTUAL): August 1, 2020
• Study Completion (ACTUAL): August 30, 2020

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (ESTIMATE): November 23, 2016

Study Record Updates

• Last Update Posted (ACTUAL): December 4, 2020
• Last Update Submitted That Met QC Criteria: December 2, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Reflux
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: 16-007005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No