The Role of Gastroesophageal Reflux in Scleroderma Pulmonary Fibrosis

Investigation Into the Role of Gastroesophageal Reflux in Pulmonary Fibrosis in Scleroderma

Scarring of the lungs is common in patients with scleroderma and is one of the main causes of death. Patients with scleroderma very frequently have problems with their gullet (esophagus), the food pipe that leads into the stomach.

Normally, a small circular muscle at the base of the esophagus opens to allow food to pass into the stomach and closes to keep the digestive fluids from flowing back up into the gullet. In patients with scleroderma, the muscle may become weak and no longer close properly. Gastroesophageal reflux (GER) is the medical term for reflux of stomach contents into the esophagus.

Our hypothesis is that small amounts of GER can move back up into the esophagus and get inhaled into the lungs, and may be one of the triggers for lung scarring. We propose to look for certain substances normally only found in the stomach in the "exhaled breath condensate" which is collected by breathing comfortably into a cooled cylinder, allowing the breath to condensate. In a smaller group of patients, we also plan to perform a bronchoalveolar lavage, a more widely studied test in which a small amount of fluid is introduced into a small part of the lungs through a fine tube, and then removed for examination, to evaluate whether the two tests provide similar measurements. We will also evaluate the correlation between these molecules and other tests, including lung function, and markers of lung scarring activity, and tests to look at how the esophagus is working so that we can get a clearer picture of how this affects patients' daily lives. Finally, we will be following up patients over time with lung function to see whether evidence of GER into the lungs is linked with a greater likelihood of worsening of lung scarring in the future.

Study Overview

• Status: Unknown
• Conditions: Gastroesophageal Reflux; Systemic Sclerosis; Interstitial Lung Disease
• Intervention / Treatment: Other: Gastro-esophageal reflux

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6NP
    • Recruiting
    • Royal Brompton Hospital
    • Contact: Elisabetta Renzoni; Phone Number: 02073528121; Email: e.renzoni@imperial.ac.uk
    • Principal Investigator: Elisabetta Renzoni
    • Sub-Investigator: Angelo De Lauretis
  • London, United Kingdom, NW3 2PF
    • Recruiting
    • Royal Free Hospital
    • Contact: Christopher Denton, MD; Phone Number: 020 77940432; Email: c.denton@ucl.ac.uk
    • Principal Investigator: Christopher Denton, MD
    • Sub-Investigator: Voon Ong

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients seen in the department of respiratory medicine or rheumatology of two teaching hospitals in London.

Description

Inclusion Criteria:

• Patients aged > 18 years
• Diagnosis of SSc (American College of Rheumatology criteria)
• Interstitial lung disease (>5% extent of ILD on HRCT)
• Only for bronchoscopy: presence of troublesome cough and/or GER symptoms and/or recurrent chest infections and/or asymmetry of ILD changes on CT

Exclusion Criteria:

• Significant communication difficulties
• Unable to perform reliable lung function tests
• Current smokers
• Only for bronchoscopy: FEV1 less than 1L or DLCO less than 30% of the predicted

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Severe/moderate acid reflux	Other: Gastro-esophageal reflux; This is an observational study. The exposure is the gastro-esophageal reflux.
Mild/absent acid reflux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurements of pepsin and pH in the Exhaled breath condensate (EBC)		Baseline
In a subgroup pf 40 patients, measurements of pepsin and bile salts in bronchoalveolar lavage (BAL)		Baseline
Serum KL-6	Serum KL-6 is a known marker of alveolar epithelial damage in SSc-ILD	Baseline
Measurements of pepsin and pH in the Exhaled breath condensate (EBC)		12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in longitudinal lung function assessment	Spirometry with total lung capacity, diffusing capacity for CO	Baseline, month 6, month 12, month 18

Collaborators and Investigators

• Sponsor: Royal Brompton & Harefield NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): April 1, 2017

Study Registration Dates

• First Submitted: December 30, 2013
• First Submitted That Met QC Criteria: May 8, 2014
• First Posted (Estimate): May 13, 2014

Study Record Updates

• Last Update Posted (Estimate): April 7, 2016
• Last Update Submitted That Met QC Criteria: April 6, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Skin Diseases; Respiratory Tract Diseases; Gastrointestinal Diseases; Stomach Diseases; Connective Tissue Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Peptic Ulcer; Duodenal Diseases; Lung Diseases; Gastroesophageal Reflux; Esophagitis, Peptic; Scleroderma, Systemic; Scleroderma, Diffuse; Pulmonary Fibrosis; Lung Diseases, Interstitial
• Other Study ID Numbers: 2013OE006B