Identifying Genetic Characteristics That Increase Risk of Primary Graft Dysfunction Following Lung Transplantation

Genetics of Primary Graft Dysfunction

Primary graft dysfunction (PGD) is a severe lung injury that can occur in the days following lung transplant surgery. The purpose of this study is to identify genetic factors that may put someone at risk for developing PGD.

Study Overview

• Status: Recruiting
• Conditions: Lung Transplantation; Primary Graft Dysfunction

Detailed Description

PGD is a severe complication that affects up to 25% of lung transplant patients following surgery. Pulmonary edema, which is an abnormal build-up of fluid in the lungs, and hypoxemia, which is low blood oxygen levels, are two common symptoms that individuals with PGD experience. Treatment for this condition is often expensive, and it is the leading cause of death following lung transplant. Many potential donors and recipients are considered unsuitable for lung transplant because of concern for the development of PGD. Therefore, the ability to accurately predict which individuals are at risk for developing PGD may allow more lung transplants to be performed. Specific characteristics in both lung donors and recipients may play an important role in determining the risk of PGD. For example, genetic variations in how the body deals with harmful chemicals called oxidants may be associated with the development of PGD. The purpose of this study is to identify the specific genetic biomarkers in donors and recipients that put individuals at risk for developing PGD following a lung transplant.

This study will enroll individuals who are undergoing lung transplantation. Blood samples will be collected from lung donors and from participants prior to surgery, immediately following surgery, and 24 hours after surgery. Study researchers will monitor participants for 72 hours following surgery for symptoms of PGD. There will be no additional study visits.

• Study Type: Observational
• Enrollment (Estimated): 1150

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Jason D. Christie, MD; Phone Number: 215-573-3209; Email: jchristi@mail.med.upenn.edu
      • Contact: Michelle Oyster, MS; Phone Number: 215-573-4767; Email: oysterm@mail.med.upenn.edu
      • Principal Investigator: Jason D. Christie, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients going under lung transplant or heart & lung transplants

Description

Inclusion Criteria:

• Undergoing lung transplant surgery

Exclusion Criteria:

- Individuals undergoing multi-organ transplantation except heart/lung transplants

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary graft dysfunction	ISHLT standard definition and grading system will be used	First 72 hours post lung transplantation

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Johns Hopkins University; National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham; University of Chicago; Columbia University; University of Pittsburgh; University of Michigan; Duke University; Vanderbilt University; Stanford University
• Investigators: Principal Investigator: Jason D. Christie, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Diamond JM, Akimova T, Kazi A, Shah RJ, Cantu E, Feng R, Levine MH, Kawut SM, Meyer NJ, Lee JC, Hancock WW, Aplenc R, Ware LB, Palmer SM, Bhorade S, Lama VN, Weinacker A, Orens J, Wille K, Crespo M, Lederer DJ, Arcasoy S, Demissie E, Christie JD; Lung Transplant Outcomes Group. Genetic variation in the prostaglandin E2 pathway is associated with primary graft dysfunction. Am J Respir Crit Care Med. 2014 Mar 1;189(5):567-75. doi: 10.1164/rccm.201307-1283OC.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: April 5, 2007
• First Submitted That Met QC Criteria: April 5, 2007
• First Posted (Estimated): April 9, 2007

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: PGD
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Reperfusion Injury; Primary Graft Dysfunction
• Other Study ID Numbers: 1380; R01HL081619 (U.S. NIH Grant/Contract)