Clinical trial NCT01406210: RESULT (REflux Surgery in Lung Transplantation) Preliminary Study Protocol
Official title: Prospective and Retrospective Study to Develop a Multi-center Randomized Study, to Determine if Prevention of GERD Related Aspiration by Surgical Fundoplication Improves Lung Allograft Function
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Reflux
Gastroesophageal Reflux Disease (GERD)
Keywords: Lung Transplant
REflux Surgery
Gastroesophageal Reflux Disease (GERD)
Fundoplication
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2011-08-01
Enrollment: 647
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male or non-pregnant female subject ≥16 years of age with a double-lung transplant who have undergone a 24-hour esophageal pH and/orimpedance probe study within 12 months prior to transplant and/or within 12 months following transplantation.

Brief summary: The purpose of the prospective study is to collect information surrounding lung transplant in order to develop a randomized study to determine if prevention of gastroesophageal reflux disease (GERD) related aspiration (stomach acid coming up from the stomach into the esophagus) by surgical fundoplication improves lung rejection. Lung transplantation has evolved into an effective treatment for patients with end-stage lung disease; however, a significant limitation to long-term survival is patients develop a condition of scarring known as chronic lung rejection, which can cause lung function to deteriorate, thereby reducing a patient's chances for survival. Preliminary research has shown a correlation between the presence of gastroesophageal reflux disease (GERD) and impaired early lung rejection as assessed by a breathing test, FEV1 (the amount of forced expired air volume in 1 second).

The Investigator is interested in learning more about this condition and the potential for aspiration (inhaling fluid) injury. The primary goal of this preliminary study will be to identify aspiration markers that are correlated with adverse clinical outcomes (increased early rejection, decreased FEV1) that may be used as inclusion criteria for the future randomized trial.

The purpose of the retrospective study is to collect information surrounding lung transplant in order to develop a randomized study to determine if prevention of gastroesophageal reflux disease (GERD) related aspiration (stomach acid coming up from the stomach into the esophagus) by surgical fundoplication improves lung rejection.

The goal of this retrospective data collection is to review the following:

1. subject outcome event rates for subjects with and without gastroesophageal reflux disease (GERD) for survival, Bronchiolitis Obliterans Syndrome (BOS), acute rejection and Forced Expiratory Volume in the first second (FEV-1),
2. the estimated treatment effect of fundoplication on the above event rates,
3. a threshold effect for Bronchiolitis Obliterans Syndrome (BOS) and/or death are more likely to occur at higher or more proximal acid or non-acid contact times.

This data will be collected in order to better design and coordinate a multicenter prospective study.

Detailed description: Prospective Group: Approximately 125 Bronchoalveolar Lavage (BAL) samples will be collected from eligible subjects at the time of clinical bronchoscopies and will be within 2 weeks of their esophageal study. The Bronchoalveolar Lavage (BAL) samples will be assayed for bile acids; pepsin, pepsinogen I and II; trypsin; gastrin, and Lipopolysaccharide (LPS) content. Short-term clinical outcome measures including acute rejection episodes, and Forced Expiratory Volume in the first second (FEV-1) at one year will be collected. Correlation between markers of reflux and aspiration will be analyzed.

Retrospective Group: Up to 800 charts within the past 5 years will be reviewed for 1) subject outcome event rates for subjects with and without Gastroesophageal Reflux Disease (GERD) for survival, Bronchiolitis Obliterans Syndrome (BOS), acute rejection and Forced Expiratory Volume in the first second (FEV-1), 2) what is the estimated treatment effect of fundoplication on the above event rates, 3) is there a threshold effect such that events such as BOS and death are more likely to occur only at higher or more proximal acid or non-acid contact times. This review will better address the role of Gastroesophageal Reflux Disease (GERD) in lung allograft failure, the clinical utility of surgical fundoplication in preventing lung allograft injury, and the role that acid and non-acid reflux as related to aspiration causes lung allograft injury as it relates to a wider population.

Eligibility criteria: Inclusion Criteria:

1. Male or non-pregnant female subject
2. 16 years of age
3. Recipient of a double-lung transplant
4. Previously have a 24-hour esophageal pH and/or impedance probe study within 12 months prior to transplant and/or within 12 months following transplantation. If the subject expired prior to 12 months from transplant date, they must have had a 24-hour esophageal pH and/or impedance probe study to be eligible in the study.

Exclusion Criteria:

1. Recipient of a single-lung transplant
2. Recipient of a re-do lung transplant
3. Recipient of a double-lung/heart or double-lung/ other organ transplant
4. Do not have a 24-hour esophageal pH and/or impedance probe study within 12 months pre-transplant or within 12 months following transplantation. The subject expired less than 12 months post transplant without having a 24-hour esophageal pH and/or impedance probe study
5. No Spirometry data is available for the subject
6. Subject who is participating in any other interventional clinical study
7. Unable to provide written informed consent or participate in long-term follow-up

Primary outcomes:
measure: BAL aspiration markers
timeFrame: 1 year
measure: Death
timeFrame: 1 year
measure: BOS
timeFrame: 1 year
measure: FEV-1
timeFrame: 1 year
measure: Acute Rejection
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
affiliation: Duke University
name: Robert D. Davis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Scott Palmer, MD
role: PRINCIPAL_INVESTIGATOR
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