The long-term goal of these studies is to understand the role that repetitive environmental exposures have in causing lung allograft injury and to substantially improve patient survival and quality of life by preventing these exposures. We propose to develop a novel interventional study that will be a multicenter, randomized clinical trial of lung transplant recipients with gastroesophageal reflux disease (GERD) who will be randomized to either receive medical management focusing on preventing gastric acid production or to undergo surgical fundoplication focusing on preventing GERD related aspiration environmental exposure to improve lung allograft function. Extensive preliminary research in animal models and lung transplant recipeints have demonstrated that GERD induced aspiration is associated with acute and chronic rejection, loss of allograft function and increased survival. In early phase I trials, the strategy of preventing aspiration by performing a fundoplication appears to lessen rejection and improve allograft function and patient survival. This proposal, we have one broad aim, Develop a randomized study, RESULT (Reflux Surgery in Lung Transplantation ) to determine if prevention of GERD related aspiration by surgical fundoplication improves lung allograft function. We intend to develop and submit to the NIH at a future date a prospective, randomized, multi- center, phase II clinical trial managed by the Duke Clinical Research Institute in which lung transplant recipients demonstrated to have GERD as assessed by pH/impedance probe study will be randomized to either receive medical management with proton pump inhibitors for maximal acid suppression or undergo surgical fundoplication as barrier to prevent reflux of any gastric contents. The primary endpoint of the study will be development of BOS-1 or death. We will accomplish the above specific aim by: 1.) Further developing our current consortium of lung transplant investigative sites by creating standard procedures and training methods to decrease the start-up period and improve data quality. 2.) Acquiring both retrospective data (prospectively collected) and prospectively collecting BAL samples from our site consortium to explore the relationship between reflux (esophageal pH/impdeance testing), aspiration (BAL markers e.g. bile, gastrin, pepsin) and patient outcomes (e.g. BOS and survival) to optimize sample size determination and inclusion/exclusion criteria for the trial. (End of Abstract)

Public Health Relevance

Lung transplant recipients suffer more rejection and worse survival than other solid organ recipients. It is highly likely that the lung's repetitive environmental exposures explain a substantial component of this difference. Strategies that reduce these environmental exposures such as fundoplication, are likely to substantially prolong both life and quality of life. Results from this planning grant will develop a future clinical trial that will substantially change practice and may have broad implications to many lung diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Planning Grant (R34)
Project #
5R34HL105422-02
Application #
8144359
Study Section
Special Emphasis Panel (ZHL1-CSR-D (S1))
Program Officer
Eu, Jerry Pc
Project Start
2010-09-16
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$683,515
Indirect Cost
Name
Duke University
Department
Other Clinical Sciences
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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