Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

June 28, 2011
September 10, 2014
September 2011
June 2013   (final data collection date for primary outcome measure)
  • 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.
Same as current
Complete list of historical versions of study NCT01406210 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
RESULT (REflux Surgery in Lung Transplantation) Preliminary Study Protocol
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

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.

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.

Observational
Observational Model: Case-Only
Not Provided
Retention:   Samples Without DNA
Description:

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.

Non-Probability Sample

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.

  • Reflux
  • Gastroesophageal Reflux Disease (GERD)
Not Provided
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
647
August 2013
June 2013   (final data collection date for primary outcome measure)

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
Both
16 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01406210
Pro00025618, 1R34HL105422-01
No
Duke University
Duke University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Robert D. Davis, MD Duke University
Principal Investigator: Scott Palmer, MD Duke University
Duke University
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP