Gluten Related Disorders in Barrett's Esophagus

Mechanisms Underlying Development of Barrett's Esophagus in Patients With Gluten Related Disorders

In a small group of people gluten, a storage protein commonly in wheat and other grains, can cause gut inflammation and symptoms like diarrhea and abdominal pain. Gluten-related disorders include celiac disease (CD) and non-celiac gluten sensitivity (NCGS) and are treated by starting a gluten free diet (GFD). Patients with CD and NCGS also more commonly experience esophageal reflux and damage to the lining of the esophagus. A potential consequence of long-standing heartburn is Barrett's esophagus (BE), a major risk factor for cancer of the esophagus.

This study aims to investigate the mechanism that leads to reflux and BE in those with gluten related disorders, and to assess if a GFD is beneficial. We will study the upper gut function and reflux activity in patients with BE both with and without a GRD disorder. Testing will occur before and after a gluten free diet is instituted. The results will help inform health care providers and patients about the connection between gluten-related disorders, reflux, BE, and the role of GFD.

Study Overview

• Status: Unknown
• Conditions: Celiac Disease; GERD; Barrett Esophagus; Gluten Sensitivity
• Intervention / Treatment: Other: Gluten free diet

Detailed Description

Perhaps patient's with gluten related disorders develop Barrett's esophagus due to non-acid reflux precipitated by upper gastrointestinal motility changes that respond to a gluten free diet; whereas patients without gluten related disorders develop Barrett's due to the accepted mechanism of acid reflux.

The primary objectives are to explore if patients with gluten-related disorders (CD and GS) may have an altered mechanism of developing Barrett's esophagus typified by increased alkali reflux compared to those without gluten-related disorders; and to determine if this mechanism (altered motility and increased non-acid reflux) responds to a gluten free diet.

Specific objectives include assessing whether patients with GRD and Barrett's esophagus have altered esophageal reflux extent, frequency, and type (assessed by pH-impedance); altered symptom profiles; differential esophageal body and sphincter pressures (assessed by manometry); aberrant gastroduodenal motility (assessed by videofluoroscopy) in comparison to patients with BE and no GRD. Finally a gluten free diet will be instituted to assess whether a gluten-free diet alters esophageal reflux extent, frequency, and type or symptom profiles in those with BE with and without a GRD.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Premysl Bercik, MD; Phone Number: 73495 905 521 2100; Email: bercikp@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 years and over
• Barrett's Esophagus diagnosis based on endoscopy and esophageal biopsies
• Patients able to comply to the study procedures, according to the investigator's own judgment

Exclusion Criteria:

• Patients who have been on a gluten free diet within the last six months
• History of bariatric surgery, fundoplication, or gastrectomy (partial or complete)
• Connective tissue disease
• Concurrent organic GI pathology other than benign polyps, haemorrhoids, lipomas, H. pylori infection, diverticulosis, and melanosis coli
• Chronic treatment with high dose opioids
• Alcohol or drug abuse
• Pregnant or breastfeeding women. Women enrolling in the study will be advised to avoid pregnancy during the course of the study by using adequate birth control such as abstinence, oral contraceptive pill, barrier contraceptives (i.e condom). If a subject becomes pregnant she will be withdrawn from the study.
• Concurrent systemic disease and/or laboratory abnormalities considered by investigators to be a risk or that could interfere with data collection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects with GRDs; An intervention of a change in diet, specifically a gluten free diet taught by a health care professional will be administered for one month's time.	Other: Gluten free diet; A month long gluten free diet
Active Comparator: Subjects without GRDs; An intervention of a change in diet, specifically a gluten free diet taught by a health-care professional will be administered for one month's time.	Other: Gluten free diet; A month long gluten free diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of non-acidic to acidic reflux events	Proportion of non-acid to acid reflux events as determined by pH-impedance	At study start and at one month after a gluten free diet

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reflux disease questionnaire	12 questions with six choices each. Results are added such that best score is 12 and worst score is 72.	At study start and one month after a gluten free diet
Esophageal motility	Manometric findings of the upper and lower sphincters and esophageal body	At study start
Upper gastrointestinal motility	Fluoroscopic findings of gastroduodenal motility	At study start
Leeds short form questionnaire	Questionnaire for dyspepsia. Nine questions with five choices each. Only eight question scores are summed. Best score is 8 and worst score is 40.	At study start and one month after a gluten free diet
Gastroesophageal reflux disease-health related quality of life instrument	11 questions. Ten of them are summed with six choices each. The best score is 0 and the worst score is 50.	At study start and one month after a gluten free diet

Collaborators and Investigators

• Sponsor: McMaster University
• Investigators: Study Director: Premysl Bercik, MD, McMaster University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2018
• Primary Completion (Anticipated): September 30, 2018
• Study Completion (Anticipated): December 30, 2018

Study Registration Dates

• First Submitted: October 18, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): March 21, 2018
• Last Update Submitted That Met QC Criteria: March 20, 2018
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Esophageal Diseases; Precancerous Conditions; Malabsorption Syndromes; Celiac Disease; Barrett Esophagus
• Other Study ID Numbers: GRD in BE

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