Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease of unknown cause and increasing prevalence in the United States. An estimated 100,000 Americans will die from IPF this year, and aside from lung transplantation, which only 1% will receive, there is no FDA-approved therapy. Over the last decade, a potential role for gastro-esophageal reflux (GER) and microaspiration in the progression of IPF has been suggested. Both acid and non-acid reflux are likely important, and preliminary data from IPF patients suggest an increased benefit of laparoscopic fundoplication over medical antacid therapy alone in slowing disease progression. Laparoscopic fundoplication has been safely performed in patients with IPF and other forms of advanced lung disease awaiting lung transplantation. These data provide a compelling argument for a trial of laparoscopic fundoplication in patients with IPF and associated GER. In the clinical proposal, we hypothesize that the reduction of abnormal GER with laparoscopic fundoplication will slow the progression of IPF as measured by the forced vital capacity (FVC). To address this hypothesis, we propose the following aims:
Aim 1 : To determine the impact of laparoscopic fundoplication on change in FVC over 48 weeks in IPF.
Aim 2 : To correlate the reduction in acid and non-acid reflux events with change in FVC over 48 weeks in IPF.
Aim 3 : To determine the safety of laparoscopic fundoplication in patients with IPF.
Aim 4 : To explore the impact of laparoscopic fundoplication on key secondary endpoints over 48 weeks in IPF. In the ancillary proposal, we will test the hypothesis that abnormal GER contributes to the profibrotic phenotype of lung epithelial cells in IPF by using molecular biomarkers in the serum, bronchoalveolar lavage, and airway epithelial cells to assess the biological relevance of the presence and treatment of abnormal GER. CLINICAL STUDY

Public Health Relevance

This proposal will test the hypothesis that the reduction of abnormal GER with laparoscopic fundoplication slows the progression of IPF, and investigate the impact of abnormal GER on the profibrotic phenotype of lung epithelial cells. We have assembled a group of researchers that is committed to this proposal's successful completion. The results of this study will directly inform the design of a future definitive phase III study and provide important insight into the pathobiology of disease progression in IPF.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
1UM1HL119089-01
Application #
8544569
Study Section
Special Emphasis Panel (ZHL1-CSR-F (M1))
Program Officer
Eu, Jerry Pc
Project Start
2013-08-01
Project End
2016-05-31
Budget Start
2013-08-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$1,075,825
Indirect Cost
$189,390
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143