Genome Transplant Dynamics
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|ClinicalTrials.gov Identifier: NCT02423070|
Recruitment Status : Recruiting
First Posted : April 22, 2015
Last Update Posted : September 14, 2021
- 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.
- To see if a new blood test can be used instead of biopsies to diagnose rejection after transplant.
- Adults 18 years and older who are on the lung or heart transplant waitlist.
- 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.
|Condition or disease|
|Thoracic Organ Transplantation|
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 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 %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 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 %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.
|Study Type :||Observational|
|Estimated Enrollment :||741 participants|
|Official Title:||Genome Transplant Dynamics|
|Actual Study Start Date :||June 25, 2015|
|Estimated Primary Completion Date :||November 1, 2024|
|Estimated Study Completion Date :||November 30, 2024|
Heart and Lung Transplant patients
- To validate the predictive accuracy and ROC characteristics of the percentage of circulating cell-free donor-derived DNA (%ccfdDNA) in a multicenter, prospective cohort study of heart-and lung-transplant patients, recruited through a consortium ... [ Time Frame: 5 years ]Fold change in %ccfdDNA at the time of biopsy-proven rejection
- 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). [ Time Frame: End of Study ]%ccfdDNA in rejection grades 1R, 2R, and 3R, %ccfdDNA at 1 month before biopsy diagnosis of AR, %ccfdDNA after treatment of AR, %ccfdDNA 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(%ccfdDNA), all-cause mortality.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423070
|Contact: Lydiah Mutumbi||(301) email@example.com|
|Contact: Sean T Agbor-Enoh, M.D.||(703) firstname.lastname@example.org|
|United States, Maryland|
|Johns Hopkins University||Recruiting|
|Baltimore, Maryland, United States, 21205|
|Contact: Jonathan Orens, M.D. 410-955-3468 email@example.com|
|United States, Virginia|
|INOVA Fairfax Hospital||Recruiting|
|Falls Church, Virginia, United States, 22042|
|Contact: Palak Shah, M.D. 703-776-2213 firstname.lastname@example.org|
|Principal Investigator:||Sean T Agbor-Enoh, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|