Genome Transplant Dynamics
- Conditions
- Thoracic Organ Transplantation
- Registration Number
- NCT02423070
- Brief Summary
Study Description:
Heart and lung transplants can save lives, but long-term success is often limited by organ rejection that is hard to detect early. This study is testing a new, non-invasive blood test that looks for small pieces of DNA from the donor organ in the patient s blood. We believe higher levels of this donor DNA may signal early rejection before damage becomes permanent.
Hypothesis:
We believe that measuring donor-derived DNA in the blood can help detect early signs of rejection and improve outcomes for transplant patients.
The study also collects genetic and biological samples to explore why some people are more at risk of complications after transplant. This may help guide future research and treatments.
Who Can Join the Study:
People receiving a heart or lung transplant (or both), age 14 and older
People who are within three months of their transplant
People who can understand and agree to take part in the study
Participants will be asked to provide blood and other samples, and some of these will be used in lab research to explore new ideas about how and why transplant rejection happens.
This research could lead to better ways to monitor and treat patients after a heart or lung transplant - and help improve long-term survival and quality of life....
- Detailed 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 donor-derived cell-free DNA (cfDNA) correlate with AR diagnosis and severity as detected by biopsy. The performance receiver operator curve (ROC) of cfDNA yielded an area under the curve (AUC) of 0.83. Using this technique, we can diagnose AR by measuring elevations in cfDNA up to 5 months before EMB-detected pathology. While these findings suggest that monitoring cfDNA 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 is 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 cfDNA for AR in a multicenter, prospective cohort study of heart and lung transplant patients, recruited through a consortium of 5 transplant centers in Washington, DC metropolitan area. The 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., chronic lung allograft dysfunction (CLAD) or chronic allograft vasculopathy (CAV). The exploratory objectives are: 1) to compare cfDNA characteristics in AMR (antibody-mediated rejection) and ACR (acute cellular rejection), 2) to study early immunological changes associated with a significant rise in cfDNA, and 3) to examine changes in microbiome architecture and other cell-free nucleic acids in rejection, 4) to determine if cfDNA trends correlate with treatment response for transplant complications, 5) to determine if the level of pre-transplant cfDNA identify patients at high risk of rejection post-transplant, 6) to determine genetic variants associated with post-transplant risk of rejection, high cfDNA levels and other complications.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 991
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To validate the predictive accuracy and ROC characteristics of circulating cell- free donor derived DNA (cfDNA) in multicenter, prospective cohort study of heart and lung transplant patients, recruited through a consortium of 5 transplant center... At the time of biopsy-proven rejection Fold change in cfDNA at the time of biopsy-proven rejection
- Secondary Outcome Measures
Name Time Method To determine the association between early graft injury caused by acute rejection and infection and the development of chronic rejection, ie.,chronic lung allograft dysfunction (CLAD) or chronic allograft vasculopathy (CAV). End of Study cfDNA in rejection grades 1R, 2R, and 3R, cfDNA at 1 month before biopsy diagnosis of AR, cfDNA after treatment of AR, cfDNA in ACR and AMR, spirometry grade of CLAD, angiographic grade of CAV, and number of AR per year, severity grade of clinically determined graft dysfunction, mean (cfDNA), all-cause mortality.
Trial Locations
- Locations (6)
MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
INOVA Fairfax Medical
🇺🇸Falls Church, Virginia, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States