The Role of Gastroesophageal Reflux in Scleroderma Pulmonary Fibrosis

• Conditions: Interstitial Lung Disease; Systemic Sclerosis; Gastroesophageal Reflux
• Interventions: Other: Gastro-esophageal reflux

• Registration Number: NCT02136394
• Lead Sponsor: Royal Brompton & Harefield NHS Foundation Trust

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-12-30
• Study Start: 2014-02
• Study First Submitted QC: 2014-05-08
• Study First Posted: 2014-05-13
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-06
• Last Update Posted: 2016-04-07
• Primary Completion: 2016-12
• Study Completion: 2017-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Severe/moderate acid reflux	Gastro-esophageal reflux	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Changes from baseline in longitudinal lung function assessment	Baseline, month 6, month 12, month 18	Spirometry with total lung capacity, diffusing capacity for CO

Trial Locations

Locations (2)

Royal free hospital; 🇬🇧 London, United Kingdom

Royal Brompton hospital; 🇬🇧 London, United Kingdom