RESULT (REflux Surgery in Lung Transplantation) Preliminary Study Protocol

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01406210
First received: June 28, 2011
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

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.


Condition
Reflux
Gastroesophageal Reflux Disease (GERD)

Study Type: Observational
Study Design: Observational Model: Case-Only
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • BAL aspiration markers [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    For the prospective study analysis, we will be assessing the relationship of gastroesophageal reflux and aspiration post lung transplantation with the occurrence of lung allograft dysfunction by reviewing BAL samples prospectively collected in approximately 125 subjects. These BAL samples will be assayed for bile acids; pepsin, pepsinogen I and II; trypsin; gastrin, and LPS content. The correlation of the aspiration biomarkers to acute rejection, BOS, death and FEV-1 at one year will be assessed.

  • Death [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    For the retrospective study, the first specific goal of data collection is outcome event rates for subjects with and without GERD for survival and the estimated treatment effect of fundoplication on the above event rates. A threshold effect for death is more likely to occur at higher or more proximal acid or non-acid contact times. Up to 5 years of follow-up data will be available for analysis with the primary comparison at one year. These data will be used to better design and coordinate a multicenter prospective study.

  • BOS [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    For the retrospective study, the second specific goal of data collection is event rates for subjects with and without GERD for BOS and the estimated treatment effect of fundoplication on the above event rates. A threshold effect for BOS is more likely to occur at higher or more proximal acid or non-acid contact times. Up to 5 years of follow-up data will be available for analysis with the primary comparison at one year. These data will be used to better design and coordinate a multicenter prospective study.

  • FEV-1 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    For the retrospective study, the third goal of data collection is evaluation of FEV-1 changes for subjects with and without GERD and the estimated treatment effect of fundoplication. Up to 5 years of follow-up data will be available for analysis with the primary comparison at one year. Data will be used to design a multicenter prospective study, address the role of 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.

  • Acute Rejection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    For the retrospective study, the final goal of data collection is evaluation of acute rejection episodes for subjects with and without GERD and the estimated treatment effect of fundoplication. Up to 5 years of follow-up data will be available for analysis with the primary comparison at one year. Data will be used to design a multicenter prospective study and to address the role of 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.


Biospecimen Retention:   Samples Without DNA

The bronchiolar lavage fluid (BALF) will be drawn during the bronchoscopy site and approximately up to 10 ml of the bronchiolar lavage (BAL) fluid will be placed in 7 storage vials (approximately 1.5 ml per vial), frozen using liquid nitrogen as the freezing agent, and shipped on dry ice to Duke University Medical Center and/or University of Toronto. Frozen samples will be stored at -80 °C to -85 °C until shipping, and the time between collection and freezing will be recorded.

The tests used to assess the bronchiolar lavage fluid (BALF) may include, but are not limited to the following: Gastrin, Pepsinogen I, Pepsinogen II, Lipopolysaccharide (LPS), Bile acids (colorimetric and enzymatic approaches), and proteome assessment by mass spectrometry.


Enrollment: 647
Study Start Date: September 2011
Study Completion Date: August 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Prospective Group
Those patients that will be consented and data collected prospectively
Retrospective Group
Those charts that will be utilized to collect retrospective data, waiver of consent will be granted by the IRBs.

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

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01406210

Locations
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Canada, Ontario
University of Toronto
Toronto, Ontario, Canada, M5G2C4
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Robert D. Davis, MD Duke University
Principal Investigator: Scott Palmer, MD Duke University
  More Information

Publications:
Hadjiliadis D, Davis RD, Lawrence CM, Rea JB, Tapson V, Brazer SR, Palmer SM. Associatioin of Bronchiolitis Obliterans Syndrome (BOS) With Gastroesophageal Reflux Disease (GERD) in Lung Transplant Recipients. Am J Respir Crit Care Med. 2001;163(5):A325.
V. Mertens1 KB, A. Paulwels1, R. Vos2 B. Vanaudenaerde2, D.E., Van Raemdonck2, 2, G.M Verleden2,3 D. Sifrim1, L.J. Dupont2,3. Aspiration of Gastric Components in Lung Transplant Recipients: Do Bile Acids Account for the Inflammatory Reaction? The Journal of Heart and Lung Transplantation. 2009, February;28(2):S214.
Lau CL, Palmer SM, Hadjiliadis D, Pappas TN, Eubanks W, Davis RD. Anti-reflux surgery improves pulmonary function in lung transplant recipients. J Heart Lung Transplant. 2002;21(1):108.

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01406210     History of Changes
Other Study ID Numbers: Pro00025618, 1R34HL105422-01
Study First Received: June 28, 2011
Last Updated: September 10, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Lung Transplant
REflux Surgery
Gastroesophageal Reflux Disease (GERD)
Fundoplication

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on October 16, 2014