Last updated on December 2019

Genome Transplant Dynamics


Brief description of study

Background
  • Some people with advanced heart and lung disease have heart and lung transplants. But the organs are often rejected. When this happens, the organ recipients must have repeated biopsies. These are invasive and expensive. Researchers want to see if a blood test can predict rejection and take the place of biopsies. The test shows how much donor DNA is in a recipient s blood.
    Objective
  • To see if a new blood test can be used instead of biopsies to diagnose rejection after transplant.
    Eligibility
  • Adults 18 years and older who are on the lung or heart transplant waitlist.
    Design
  • Participants will have about 4 teaspoons of blood drawn from the arm before having their transplant.
  • Researchers will collect demographic data about participants. They will also collect basic medical information about their condition.
  • After surgery, while still in the hospital, participants will have 2 teaspoons of blood drawn twice a week until they go home.
  • At each biopsy visit after the transplant, participants will have 4 teaspoons of blood drawn for testing for up to 5 years.

Detailed Study Description

Acute rejection (AR) occurs within the first 6 months after transplantation in 20 percent of heart-transplant patients and in 50 percent of lung-transplant patients. Given the often silent clinical presentation of AR, these patients require monitoring with repeated invasive and costly endomyocardial (EMB) or transbronchial biopsies (TBBx). Since organ transplantation is essentially genomic transplantation, our prior studies leveraged the use of distinctive graft and recipient genotype single-nuclear polymorphisms (SNPs) to barcode donor DNA circulating in recipient serum. We have shown that levels of donor DNA measured as the percentage of circulating cell-free donor-derived DNA (%ccfdDNA) correlates with AR diagnosis and severity as detected by biopsy. The performance receiver operator curve (ROC) of %ccfdDNA yielded an area under the curve (AUC) of 0.83. Using this technique, we can diagnose AR by measuring elevations in %ccfdDNA up to 5 months before EMB-detected pathology. While these findings suggest that monitoring %ccfdDNA may offer a high-performing, non-invasive, and early diagnostic tool of AR, further validation studies are required to determine its clinical utility. The ability to diagnose AR earlier than possible with a biopsy offers an opportunity to investigate the pathogenesis of rejection as well as to identify potential AR biomarkers. Thus, the primary objective of this study is to validate the predictive accuracy and ROC characteristics of %ccfdDNA for AR in a multicenter, prospective cohort study of heart- and lung-transplant patients, recruited through a consortium of 5 transplant centers in the Washington, DC metropolitan area. The major secondary objective is to determine the association between early graft injury caused by acute rejection and infection and the development of chronic rejection, i.e., bronchiolitis obliterans syndrome (BOS) or chronic allograft vasculopathy (CAV). The exploratory secondary objectives are: 1) to compare %ccfdDNA characteristics in AMR (antibody-mediated rejection) and ACR (acute cellular rejection), 2) to study early immunological changes associated with a significant rise in %ccfdDNA, and 3) to examine changes in microbiome architecture and other cell-free nucleic acids in rejection.

Clinical Study Identifier: NCT02423070

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