Gastric Neuromuscular Function in GERD

Exploring the Role of Gastric Neuromuscular Function in the Pathophysiology of Proton Pump Inhibitor (PPI) Refractory Gastresophageal Reflux Disease (GERD)

Bodysurface gastric mapping (BSGM) will be used to assess gastric neuromuscular function in healthy controls and patients with medical refractory gastroesophageal reflux disease (GERD).

Participants will undergo BSGM for 4-hours in addition to high resolution manometry (HRM), pH-impedance monitoring, and gastric emptying breath test.

Study Overview

• Status: Recruiting
• Conditions: GERD
• Intervention / Treatment: Device: Body Surface Gastric Mapping

Detailed Description

This is a clinical trial of a non-invasive BSGM medical device (Gastric Alimetry) in patients with medical refractory GORD and healthy controls to determine the differences in gastric electrical activity, and correlate with adjacent measurements of gastro-esophageal function.

Patients referred to the Functional Gut Clinic for standard care investigation of GORD with HRM and pH-impedance monitoring will be recruited. Healthy volunteers will be recruited via advertisement.

All patients and healthy volunteers will undergo BSGM at the research site, which lasts around 4.5 hours. After a 0.5 hour baseline, subjects will undergo HRM and pH-impedance monitoring concomitantly. A test meal of porridge with C13 labelled octanoic acid will be consumed with BSGM and breath samples recorded for 4.0 hours after meal completion. The HRM catheter will be removed after 1.0 hour from finishing the test meal whist the pH-impedance monitoring will continue for the remainder of the site visit and for the remainder of the 24-hour study period whilst the subject is at home to quantify reflux.

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

Contacts and Locations

• Study Contact: Name: Anthony Hobson, PhD; Phone Number: 01613027777; Email: anthony@thefunctionalgutclinic.com

Study Locations

• United Kingdom
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M3 4BG
      • Recruiting
      • The Functional Gut Clinic
      • Contact: Jordan Haworth, BSc; Phone Number: 01613027777; Email: jordan@functionalgutdiagnostics.com
      • Sub-Investigator: Jordan J Haworth, BSc
      • Sub-Investigator: Sam Treadway, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Healthy controls

Inclusion Criteria:

• Aged 18-70 years old
• BMI 18-35
• Able to understand written and spoken English
• Able to provide written consent
• Able to understand risks and benefits

Exclusion Criteria:

• Antacid use (e.g. PPI, H2RA or Gaviscon) within last 12-months
• Active use of other medications known to impact gastric motility
• Upper GI symptoms including but not limited to heartburn, regurgitation, epigastric pain, nausea and bloating
• Significant medical condition
• History of skin allergies or hypersensitivity
• Active abdominal wounds or abrasions, fragile skin
• Current pregnancy
• Vulnerable group e.g. prisoners/cognitive impairment/institutionalised individuals
• Regular cannabis users (unable to abstain for 7-days)
• Opioid user
• Unable to use a tablet device

GORD patients

Inclusion Criteria

• Referred for 24-hour pH-impedance monitoring
• Aged 18-70 years old
• BMI 18-35
• Able to understand written and spoken English
• Able to provide written consent
• Able to understand risks and benefits

Exclusion Criteria

• Systemic or metabolic disorder known to cause gastric dysmotility other than diabetes (e.g. scleroderma, multiple sclerosis, hyperthyroidism).
• History of upper GI surgery or hiatal hernia (>5cm, paraesophageal, or 'large' on endoscopy report)
• Diabetic and on insulin
• Proven mechanical bowel obstruction
• History of skin allergies or hypersensitivity
• Active abdominal wounds or abrasions, fragile skin
• Current pregnancy
• Vulnerable group - prisoners/cognitive impairment/institutionalised individuals
• Regular cannabis users (unable to abstain for 7-days)
• Opioid user
• Unable to use a tablet device

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Patients with medical refractory GERD; Participants undergo BSGM for 4.5 hours with simultaneous oesophageal manometry, pH-impedance monitoring and gastric emptying breath tests. Following completion, participants continue with ambulatory pH-impedance monitoring for a further 24-hours. Participants undergo a hydrogen and emthane breath test on a seperate day.	Device: Body Surface Gastric Mapping; 64-channel electrode array placed on the outer abdomen
ACTIVE_COMPARATOR: Healthy controls without gastrointestinal symptoms; Participants undergo BSGM for 4.5 hours with simultaneous oesophageal manometry, pH-impedance monitoring and gastric emptying breath tests. Following completion, participants continue with ambulatory pH-impedance monitoring for a further 24-hours.	Device: Body Surface Gastric Mapping; 64-channel electrode array placed on the outer abdomen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in BSGM parameters between GORD and healthy controls	Gastric Alimetry Rhythm Index (Normal >0.25)	24-hours
Difference in BSGM parameters between GORD and healthy controls	Prinicpal Gastric Frequency (Normal: 2.65-3.35cpm)	24-hours
Difference in BSGM parameters between GORD and healthy controls	Fed:Fasted Amplitude ratio (Normal: >1.08)	24-hours
Difference in BSGM parameters between GORD and healthy controls	Average Amplitude (Normal: 20-70 microvolts)	24-hours
Difference in BSGM parameters between GORD and healthy controls	% of retrograde activity	24-hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normal reference ranges for gastric emptying and BSGM	T lag and T 1/2 time (minutes)	24-hours
Correlate reflux event frequency with Gastric Alimetry Rhythm Index	Frequency of reflux events with Gastric Alimetry Rhythm Index	24-hours
Correlate reflux event frequency with Prinicpal Gastric Frequency (cpm)	Frequency of reflux events with Prinicpal Gastric Frequency (cpm)	24-hours
Correlate reflux event frequency with Fed:Fasted Amplitude ratio	Frequency of reflux events with Fed:Fasted Amplitude ratio	24-hours
Correlate reflux event frequency with Average Amplitude	Frequency of reflux events with Average Amplitude (microvolts)	24-hours
Correlate reflux event frequency with % of retrograde activity	Frequency of reflux events with % of retrograde activity	24-hours
Correlate symptom severity with BSGM parameters	Real time discrete (vomiting, belching, reflux counts) and continuous (Nausea, bloating, upper gut pain, heartburn, stomach burn and excessive fullness) gastrointestinal symptom scores at both pre- and post-prandial time periods determined by a series of multiple 10-point symptom severity scales integrated within the validated Gastric Alimetry iOS Application with Gastric Alimetry Rhythm Index	24-hours
Correlate quality of life with BSGM parameters	Total symptom burden scores according to the PAGI-QOL with Gastric Alimetry Rhythm Index	24-hours
Correlate the results of gastric emptying with BSGM parameters	T lag and T 1/2 (minutes) with ith Gastric Alimetry Rhythm Index	24-hours
Correlate the results of oesophageal manometry with BSGM parameters	Distal contractile integral (mmHg.s.cm) with Gastric Alimetry Rhythm Index	24-hours
Correlate the results of oesophageal manometry with Gastric Alimetry Rhythm Index	Integrated relaxation pressure (mmHg) with Gastric Alimetry Rhythm Index	24-hours
Correlate the results of oesophageal manometry with Prinicpal Gastric Frequency	Integrated relaxation pressure (mmHg) with Prinicpal Gastric Frequency	24-hours
Correlate the results of oesophageal manometry with Prinicpal Gastric Frequency	Integrated relaxation pressure (mmHg) with % of retrograde activity	24-hours
Correlate the results of oesophageal manometry with Gastric Alimetry Rhythm Index	Frequency of transient lower oesophageal sphincter relaxation (TLOSRs) with Gastric Alimetry Rhythm Index	24-hours
Correlate the results of oesophageal manometry with Gastric Alimetry Rhythm Index	Frequency of transient lower oesophageal sphincter relaxation (TLOSRs) with Prinicpal Gastric Frequency	24-hours
Correlate the results of oesophageal manometry with % of retrograde activity	Frequency of transient lower oesophageal sphincter relaxation (TLOSRs) with % of retrograde activity	24-hours
Correlate the results of hydrogen and methane breath testing with Gastric Alimetry Rhythm Index	Total gas production (AUC ppm) with Gastric Alimetry Rhythm Index	7 days

Collaborators and Investigators

• Sponsor: The Functional Gut Clinic

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2022
• Primary Completion (ANTICIPATED): October 1, 2023
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (ACTUAL): February 8, 2023

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: January 31, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: FGC-22-002

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
• product manufactured in and exported from the U.S.: No