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

Sponsor

Stanford University (Other)

Overall Status

Completed

CT.gov ID

NCT01985412

Collaborator

Kaiser Foundation Research Institute (Other)

Enrollment

Locations

Duration (Months)

32.5

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Transplant Rejection Lung Transplant Rejection

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 Design

Study Type:

Observational

Actual Enrollment :

65 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Genome Transplant Dynamics: Non-Invasive Sequencing-Based Diagnosis of Rejection

Study Start Date :

Mar 1, 2010

Actual Primary Completion Date :

Sep 29, 2013

Actual Study Completion Date :

Sep 29, 2013

Arms and Interventions

Arm	Intervention/Treatment
Adult Heart Transplant Recipients Patients >18 yrs old that received a heart-only transplant and are followed at Stanford Hospital
Pediatric Heart Transplant Recipients Patients <18 yrs old that received a heart-only transplant and are followed at Lucile Packard Hospital
Adult Lung Transplant Recipients Patients >18 yrs old that received a lung-only transplant and are followed at Stanford Hospital
Pediatric Lung Transplant Recipients Patients <18 yrs old that received a lung-only transplant and are followed at Lucile Packard Hospital
Kaiser Adult Heart Transplant Recipients Patients >18 yrs old that received a heart-only transplant at Stanford Hospital but are followed at Kaiser Permanente in Santa Clara

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Patients wait-listed for multiple organ transplantation (e.g. heart-kidney, heart-liver, heart and lung.)
Unable or unwilling to return to Stanford for biopsy and follow-up procedures
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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente Northern California	Santa Clara	California	United States	95051
2	Stanford University Hospital and Clinics	Stanford	California	United States	94305