Genome Transplant Dynamics: Non-invasive Sequencing-based Diagnosis of Rejection

Completed

• Conditions: Lung Transplant Rejection; Cardiac Transplant Rejection

• Registration Number: NCT01985412
• Lead Sponsor: Stanford University

Brief Summary

The purpose of this study is to determine whether shotgun sequencing technology, which can be used to detect donor DNA in recipient plasma, can be used as a rapid, accurate, non-invasive method to detect Acute Cellular Rejection (ACR) after heart transplantation. Currently, all heart transplant recipients undergo invasive heart biopsies to diagnose ACR. Thus, there is an ongoing need to monitor patients for the development of acute and chronic rejection, with the primary goal of non-invasive early detection and treatment to prevent organ damage.

Detailed Description

Previous attempts to develop a non-invasive marker of graft rejection have focused on recipient-specific immune responses, and thus have inherent limitations in both sensitivity and selectivity, especially in distinguishing rejection from infection. The investigators' goal is to use a novel DNA sequencing technology to develop a rapid, inexpensive, and non-invasive method for monitoring organ transplant recipients for graft rejection. The investigators' research is driven by the fact that acute and chronic rejection of thoracic organ transplants remain major causes of patient morbidity and mortality, and require intense resource utilization. The investigators' novel approach is the first to focus on a donor-specific marker of acute rejection. The investigators will use high throughput next generation sequencing to monitor the proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection. This approach is enabled by the fact that an organ transplant is also effectively a genome transplant, and by monitoring single nucleotide polymorphisms that are specific to the donor's genome (and are not shared with the recipient's genome) one can measure the relative health of the transplanted organ. The investigators' preliminary studies show that cell-free donor DNA levels in the serum of heart transplant recipients increase prior to diagnosis of acute rejection by endomyocardial biopsy, but remain at stable low levels in the absence of acute rejection.

Study Timeline

• Study Start: 2010-03
• Study First Submitted: 2013-05-28
• Primary Completion: 2013-09-29
• Study Completion: 2013-09-29
• Study First Submitted QC: 2013-11-08
• Study First Posted: 2013-11-15
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-02
• Last Update Posted: 2019-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

1. All ages of heart or lung transplant recipients
2. Recipients of re-do heart or re-do lung transplants

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Exclusion Criteria

1. Patients wait-listed for multiple organ transplantation (e.g. heart-kidney, heart-liver, heart and lung.)
2. Unable or unwilling to return to Stanford for biopsy and follow-up procedures
3. Followed by Palo Alto VA Hospital after transplant surgery (VA patients are transplanted at Stanford, but all subsequent clinical care is performed at VA hospitals)

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.	The outcome measure is assessed for each patient up to 5 years post-transplant. Sampling timepoints include: Days 1, 2, 3, Weeks 1, 2, 4, 6, 8, 10, 12, Months 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 and quarterly through year 5	We will use high throughput next generation sequencing to monitor the proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.

Trial Locations

Locations (2)

Stanford University Hospital and Clinics; 🇺🇸 Stanford, California, United States

Kaiser Permanente Northern California; 🇺🇸 Santa Clara, California, United States