Clinical trial NCT02136394: The Role of Gastroesophageal Reflux in Scleroderma Pulmonary Fibrosis
Official title: Investigation Into the Role of Gastroesophageal Reflux in Pulmonary Fibrosis in Scleroderma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Interstitial Lung Disease
Systemic Sclerosis
Gastroesophageal Reflux
Lead sponsor: Royal Brompton & Harefield NHS Foundation Trust
Sponsor class: OTHER
First posted: 2014-05-13
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients seen in the department of respiratory medicine or rheumatology of two teaching hospitals in London.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Measurements of pepsin and pH in the Exhaled breath condensate (EBC)
timeFrame: Baseline
measure: In a subgroup pf 40 patients, measurements of pepsin and bile salts in bronchoalveolar lavage (BAL)
timeFrame: Baseline
measure: Serum KL-6
timeFrame: Baseline
measure: Measurements of pepsin and pH in the Exhaled breath condensate (EBC)
timeFrame: 12 months
Secondary outcomes:
measure: Changes from baseline in longitudinal lung function assessment
timeFrame: Baseline, month 6, month 12, month 18
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal free hospital
city: London
country: United Kingdom
facility: Royal Brompton hospital
Study officials:
References: