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

October 2, 2019 updated by: Kiran Khush, Stanford University

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

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.

Study Overview

Status

Completed

Conditions

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 Type

Observational

Enrollment (Actual)

65

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Santa Clara, California, United States, 95051
        • Kaiser Permanente Northern California
      • Stanford, California, United States, 94305
        • Stanford University Hospital and Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Stanford and Lucille Packard adult and pediatric, lung or heart transplant recipients and Kaiser adult heart transplant recipients.

Description

Inclusion Criteria:

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

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.
Time Frame: 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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

Kaiser Foundation Research Institute

Investigators

  • Principal Investigator: Kiran Khush, MD MAS FACC, Stanford University Hospital and Clinics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2010

Primary Completion (Actual)

September 29, 2013

Study Completion (Actual)

September 29, 2013

Study Registration Dates

First Submitted

May 28, 2013

First Submitted That Met QC Criteria

November 8, 2013

First Posted (Estimate)

November 15, 2013

Study Record Updates

Last Update Posted (Actual)

October 4, 2019

Last Update Submitted That Met QC Criteria

October 2, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 17666

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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