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

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ClinicalTrials.gov Identifier: NCT01985412
Recruitment Status : Completed
First Posted : November 15, 2013
Last Update Posted : October 4, 2019
Sponsor:
Collaborator:
Kaiser Foundation Research Institute
Information provided by (Responsible Party):
Kiran Khush, 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.

Condition or disease
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.

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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 : March 2010
Actual Primary Completion Date : September 29, 2013
Actual Study Completion Date : September 29, 2013

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



Primary Outcome Measures :
  1. 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.


Biospecimen Retention:   Samples With DNA
A single whole blood specimen from both the donor and recipient of the organ prior to transplant. Additionally, blood samples are taken post-transplant at specified timepoints and spun down into a plasma, buffycoat layer. The plasma and buffycoat are retained while the rest is discarded.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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)

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): NCT01985412


Locations
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United States, California
Kaiser Permanente Northern California
Santa Clara, California, United States, 95051
Stanford University Hospital and Clinics
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Kaiser Foundation Research Institute
Investigators
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Principal Investigator: Kiran Khush, MD MAS FACC Stanford University Hospital and Clinics

Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kiran Khush, Kiran Khush, MD, MAS, FACC, Stanford University
ClinicalTrials.gov Identifier: NCT01985412     History of Changes
Other Study ID Numbers: 17666
First Posted: November 15, 2013    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019
Keywords provided by Kiran Khush, Stanford University:
Rejection
Transplant
Cardiac
Pulmonary
Heart
Lung
Cell-Free DNA
cfDNA
Cell
Free
DNA
Biopsy
Non-Invasive