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Genome Transplant Dynamics

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ClinicalTrials.gov Identifier: NCT02423070
Recruitment Status : Recruiting
First Posted : April 22, 2015
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Brief Summary:

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.

Condition or disease
Thoracic Organ Transplantation

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 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.

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Study Type : Observational
Estimated Enrollment : 495 participants
Observational Model: Cohort
Time Perspective: Prospective
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



Primary Outcome Measures :
  1. 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 ]
    Our approach is a multicenter, prospective cohort study involving 5 local transplant centers, all of which have pre-transplant and post-transplant clinics. All transplant waitlist patients have regular clinic monitoring visits while they transplant. Occasionally, pre-transplantpatients with high disease burden are hospitalized untiltransplantation. After transplantation, patients arehospitalized for an average of 1-2 weeks. After discharge, patients are then followed regularly in transplant clinics and undergo scheduledbiopsies to monitor for rejection. Patients with signs of graft dysfunction undergo unscheduled biopsy and/or clinic visits. Clinic and biopsy schedules for each center are shown in Appendix III.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
-Lung and heart transplant candidates@@@-Subjects who have undergone lung or heart transplants within 3 months of transplantation.@@@-18 years and older@@@-Able to understand and willing to sign the informed consent form
Criteria
  • INCLUSION CRITERIA:
  • Lung and heart transplant candidates
  • Subjects who have undergone lung or heart transplants within 3 months of transplantation.
  • 18 years and older
  • Able to understand and willing to sign the informed consent form

EXCLUSION CRITERIA:

-Pregnancy


Information from the National Library of Medicine

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


Contacts
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Contact: Sean T Agbor-Enoh, M.D. (703) 677-4630 agborenohst@mail.nih.gov

Locations
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United States, District of Columbia
MedStar Health Institutions Recruiting
Washington, District of Columbia, United States
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21205
University of Maryland at Baltimore/MPRC Recruiting
Catonsville, Maryland, United States, 21228
United States, Virginia
INOVA Fairfax Hospital Recruiting
Falls Church, Virginia, United States, 22042
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23284
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Sean T Agbor-Enoh, M.D. National Institutes of Health Clinical Center (CC)

Publications:
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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT02423070     History of Changes
Other Study ID Numbers: 999915115
15-H-N115
First Posted: April 22, 2015    Key Record Dates
Last Update Posted: June 11, 2019
Last Verified: June 7, 2019

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Cell-free DNA
Acute Rejection
Thoracic Organ Transplantation
Non-Invasive Testing
Chronic Rejection