Genome Transplant Dynamics: Non-invasive Sequencing-based Diagnosis of Rejection (GTD)
2019年10月2日 更新者: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.
研究概览
详细说明
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.
研究类型
观察性的
注册 (实际的)
65
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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California
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Santa Clara、California、美国、95051
- Kaiser Permanente Northern California
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Stanford、California、美国、94305
- Stanford University Hospital and Clinics
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 孩子
- 成人
- 年长者
接受健康志愿者
不
有资格学习的性别
全部
取样方法
非概率样本
研究人群
Stanford and Lucille Packard adult and pediatric, lung or heart transplant recipients and Kaiser adult heart transplant recipients.
描述
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)
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
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Adult Heart Transplant Recipients
Patients >18 yrs old that received a heart-only transplant and are followed at Stanford Hospital
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Pediatric Heart Transplant Recipients
Patients <18 yrs old that received a heart-only transplant and are followed at Lucile Packard Hospital
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Adult Lung Transplant Recipients
Patients >18 yrs old that received a lung-only transplant and are followed at Stanford Hospital
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Pediatric Lung Transplant Recipients
Patients <18 yrs old that received a lung-only transplant and are followed at Lucile Packard Hospital
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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
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Proportion of cell-free donor DNA to recipient DNA in the recipient's blood stream as a marker of rejection.
大体时间: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
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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.
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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
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Kiran Khush, MD MAS FACC、Stanford University Hospital and Clinics
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- 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.
- Keller M, Bush E, Diamond JM, Shah P, Matthew J, Brown AW, Sun J, Timofte I, Kong H, Tunc I, Luikart H, Iacono A, Nathan SD, Khush KK, Orens J, Jang M, Agbor-Enoh S. Use of donor-derived-cell-free DNA as a marker of early allograft injury in primary graft dysfunction (PGD) to predict the risk of chronic lung allograft dysfunction (CLAD). J Heart Lung Transplant. 2021 Jun;40(6):488-493. doi: 10.1016/j.healun.2021.02.008. Epub 2021 Feb 20.
- Agbor-Enoh S, Jackson AM, Tunc I, Berry GJ, Cochrane A, Grimm D, Davis A, Shah P, Brown AW, Wang Y, Timofte I, Shah P, Gorham S, Wylie J, Goodwin N, Jang MK, Marishta A, Bhatti K, Fideli U, Yang Y, Luikart H, Cao Z, Pirooznia M, Zhu J, Marboe C, Iacono A, Nathan SD, Orens J, Valantine HA, Khush K. Late manifestation of alloantibody-associated injury and clinical pulmonary antibody-mediated rejection: Evidence from cell-free DNA analysis. J Heart Lung Transplant. 2018 Jul;37(7):925-932. doi: 10.1016/j.healun.2018.01.1305. Epub 2018 Jan 31.
- 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 21;155(5):1178-87. doi: 10.1016/j.cell.2013.10.034.
- 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(241):241ra77. doi: 10.1126/scitranslmed.3007803.
- Vollmers C, De Vlaminck I, Valantine HA, Penland L, Luikart H, Strehl C, Cohen G, Khush KK, Quake SR. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study. PLoS Med. 2015 Oct 14;12(10):e1001890. doi: 10.1371/journal.pmed.1001890. eCollection 2015 Oct.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2010年3月1日
初级完成 (实际的)
2013年9月29日
研究完成 (实际的)
2013年9月29日
研究注册日期
首次提交
2013年5月28日
首先提交符合 QC 标准的
2013年11月8日
首次发布 (估计)
2013年11月15日
研究记录更新
最后更新发布 (实际的)
2019年10月4日
上次提交的符合 QC 标准的更新
2019年10月2日
最后验证
2019年10月1日
更多信息
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