The Role of Gastroesophageal Reflux in Scleroderma Pulmonary Fibrosis

Sponsor

Royal Brompton & Harefield NHS Foundation Trust (Other)

Overall Status

Unknown status

CT.gov ID

NCT02136394

Collaborator

(none)

100

Enrollment

Locations

37.9

Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Interstitial Lung Disease Systemic Sclerosis Gastroesophageal Reflux	Other: Gastro-esophageal reflux

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Feb 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Apr 1, 2017

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

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 [Baseline]
Serum KL-6 is a known marker of alveolar epithelial damage in SSc-ILD
Measurements of pepsin and pH in the Exhaled breath condensate (EBC) [12 months]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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