Genome Transplant Dynamics

NCT ID: NCT02423070

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 991 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-06-25
• Study Completion Date: 2034-11-30

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.

Conditions

Thoracic Organ Transplantation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Cohort 1

Heart and Lung Transplant patients

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Lung and heart transplant candidates. Dual organ transplants such as those that include lung or heart PLUS any other organ are also considered for enrollment.
• Subjects who have undergone lung or heart transplants and are within 3 months of transplantation.
• 14 years and older
• Able to understand and be willing to sign the informed consent form. Subjects undergoing a double transplant will sign a single consent.
• Retransplant candidates will be considered as a new transplants. These subjects will be approached for enrollment and if they consent to participate, they will be assigned a different SSPIN.

Exclusion Criteria

-Pregnancy

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sean T Agbor-Enoh, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status: COMPLETED

Johns Hopkins University

Baltimore, Maryland, United States

Site Status: RECRUITING

University of Maryland

Baltimore, Maryland, United States

Site Status: TERMINATED

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

INOVA Fairfax Medical

Falls Church, Virginia, United States

Site Status: RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

Sean T Agbor-Enoh, M.D.

Role: CONTACT

agborenohst@mail.nih.gov

(703) 677-4630

Facility Contacts

Jonathan Orens, M.D.

Role: primary

jorens@jhmi.edu

410-955-3468

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Role: primary

ccopr@nih.gov

800-411-1222 ext. TTY dial 711

Steven Nathan, M.D.

Role: primary

steven.nathan@inova.org

703-776-2213

References

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Other Identifiers

15-H-N115

Identifier Type: -

Identifier Source: secondary_id

999915115

Identifier Type: -

Identifier Source: org_study_id