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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Activity of genes in donor tissues that are involved in inflammation are thought to be involved with early organ dysfunction, increased immune responses in transplant recipients, and organ rejection. The purpose of this study is to determine the relationship between genetic expression in donor and recipient tissue with transplant survival. Participants in this study will have received heart, lung, liver, or kidney transplants.
Inflammation and injuries to transplanted organs during the immediate post-operative period may be linked to early organ dysfunction and higher rates of transplant rejection in the recipient. Currently, mRNA expression of proinflammatory genes in donor tissues is thought to be a risk factor for early organ transplant dysfunction, increased expression of the recipients cell-mediated immunity genes, and organ rejection. The purpose of this study is to test the association between proinflammatory mRNA expression in donor samples and subsequent development of early organ dysfunction in kidney, lung, and liver transplant recipients. This study will also test the effects of proinflammatory mediators expressed in the transplanted organ pre- and post-reperfusion on organ rejection and genes expressed in cell mediated immune responses. This will be achieved by identifying the proinflammatory immune responses and their mechanisms.
This study will consist of up to 11 study visits over a period of 2 years. The baseline visit will occur 24 hours prior to organ transplantation. Follow-up visits will occur daily for Days 1 to 3 (for lung transplant recipients only) and on Day 7, Week 6, and Months 3, 6, 9, 12, 18, and 24 post-transplant. At the baseline visit, a physical exam, medical history, demographics, vital signs measurements, blood collection, and collection of donor tissue sample will occur. For most or all other study visits, medication and adverse events tracking and blood collection will occur. Depending on the transplant type, participants will undergo the following procedures:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Kidney transplants | patients from 5 specific sites | ||
| Liver transplants | patients from 5 specific sites | ||
| Heart transplants | patients from 5 specific sites | ||
| Lung transplants | patients from 5 specific sites |
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| Measure | Description | Time Frame |
|---|---|---|
| Association between proinflammatory mRNA expression in donor samples and subsequent development of early organ dysfunction in the immediate period following transplantation | Within first 7 days after transplant | |
| Association of mRNA expression of proinflammatory mediatros in the transplanted organ in the immediate pre and post-reperfusion period with subsequent incidence of acute rejection and expression of genes involved in cell mediated immunity | 12 months after transplant |
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Inclusion Criteria for all participants:
Inclusion Criteria for Kidney or Liver Transplant Participants:
Inclusion Criteria for Heart or Lung Transplant Participants:
Exclusion Criteria for All Participants:
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Transplant patients evaluated for the association between proinflammatory mRNA expression from donor samples and subsequent development of early organ dysfunction
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| Name | Affiliation | Role |
|---|---|---|
| Abraham Shaked, MD, PhD | University of Pennsylvania Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern Memorial Hospital (kidney and liver) | Chicago | Illinois | 60611 | United States | ||
| Cornell University Medical College (kidney) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11867677 | Background | Fox-Marsh A, Harrison LC. Emerging evidence that molecules expressed by mammalian tissue grafts are recognized by the innate immune system. J Leukoc Biol. 2002 Mar;71(3):401-9. | |
| 9626898 | Background | Isobe M, Suzuki J. New approaches to the management of acute and chronic cardiac allograft rejection. Jpn Circ J. 1998 May;62(5):315-27. doi: 10.1253/jcj.62.315. |
| Label | URL |
|---|---|
| Click here for the Clinical Trials in Organ Transplantation (CTOT) public Web site | View source |
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Blood and tissue samples to evaluate the heart, kidney, liver, and lung
| Ithaca |
| New York |
| 14850 |
| United States |
| Columbia University (lung and liver) | New York | New York | 10032 | United States |
| University of Pennsylvania (heart, kidney, liver, lung) | Philadelphia | Pennsylvania | 19104 | United States |
| University of Wisconsin (heart and lung) | Madison | Wisconsin | 53706 | United States |
| 17168794 | Background | Jiang S, Lechler RI. CD4+CD25+ regulatory T-cell therapy for allergy, autoimmune disease and transplant rejection. Inflamm Allergy Drug Targets. 2006 Dec;5(4):239-42. doi: 10.2174/187152806779010981. |
| 11805720 | Background | Kaplan B, Srinivas TR, Meier-Kriesche HU. Factors associated with long-term renal allograft survival. Ther Drug Monit. 2002 Feb;24(1):36-9. doi: 10.1097/00007691-200202000-00007. |
| 17202291 | Background | Lande JD, Patil J, Li N, Berryman TR, King RA, Hertz MI. Novel insights into lung transplant rejection by microarray analysis. Proc Am Thorac Soc. 2007 Jan;4(1):44-51. doi: 10.1513/pats.200605-110JG. |
| 16498661 | Background | Reding R, Gras J, Truong DQ, Wieers G, Latinne D. The immunological monitoring of alloreactive responses in liver transplant recipients: a review. Liver Transpl. 2006 Mar;12(3):373-83. doi: 10.1002/lt.20704. |
| 14563315 | Background | Zheng XX, Sanchez-Fueyo A, Sho M, Domenig C, Sayegh MH, Strom TB. Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance. Immunity. 2003 Oct;19(4):503-14. doi: 10.1016/s1074-7613(03)00259-0. |
| 23710539 | Result | Cantu E, Lederer DJ, Meyer K, Milewski K, Suzuki Y, Shah RJ, Diamond JM, Meyer NJ, Tobias JW, Baldwin DA, Van Deerlin VM, Olthoff KM, Shaked A, Christie JD; CTOT Investigators. Gene set enrichment analysis identifies key innate immune pathways in primary graft dysfunction after lung transplantation. Am J Transplant. 2013 Jul;13(7):1898-904. doi: 10.1111/ajt.12283. Epub 2013 May 24. |
| 20677285 | Derived | Olthoff KM, Kulik L, Samstein B, Kaminski M, Abecassis M, Emond J, Shaked A, Christie JD. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010 Aug;16(8):943-9. doi: 10.1002/lt.22091. |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D007674 | Kidney Diseases |
| D008107 | Liver Diseases |
| D017093 | Liver Failure |
| D008171 | Lung Diseases |
| D012059 | Rejection, Psychology |
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D004066 | Digestive System Diseases |
| D048550 | Hepatic Insufficiency |
| D012140 | Respiratory Tract Diseases |
| D012919 | Social Behavior |
| D001519 | Behavior |
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