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

Lung Transplant Rejection Clinical Trial

— GTD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01985412
• Other study ID #: 17666
• Status: Completed
• Start date: March 2010
• Est. completion date: September 29, 2013

Study information

• Verified date: October 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: September 29, 2013
• Est. primary completion date: September 29, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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)

Related Conditions & MeSH terms

• Cardiac Transplant Rejection
• Lung Transplant Rejection

Locations

Country	Name	City	State
United States	Kaiser Permanente Northern California	Santa Clara	California
United States	Stanford University Hospital and Clinics	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Kaiser Foundation Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (3)

De Vlaminck I, Khush KK, Strehl C, Kohli B, Luikart H, Neff NF, Okamoto J, Snyder TM, Cornfield DN, Nicolls MR, Weill D, Bernstein D, Valantine HA, Quake SR. Temporal response of the human virome to immunosuppression and antiviral therapy. Cell. 2013 Nov — View Citation

De Vlaminck I, Valantine HA, Snyder TM, Strehl C, Cohen G, Luikart H, Neff NF, Okamoto J, Bernstein D, Weisshaar D, Quake SR, Khush KK. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. 2014 Jun 18;6(24 — View Citation

Snyder TM, Khush KK, Valantine HA, Quake SR. Universal noninvasive detection of solid organ transplant rejection. Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6229-34. doi: 10.1073/pnas.1013924108. Epub 2011 Mar 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.	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

External Links

•   Circulating Cell-Free DNA Enables Noninvasive Diagnosis of Heart Transplant Rejection
•   Temporal Response of the Human Virome to Immunosuppression and Antiviral Therapy