Effects of Donor and Recipient Genetic Expression on Heart, Lung, Liver, or Kidney Transplant Survival

Kidney Transplantation Clinical Trial

Official title:

Correlation of Donor Proinflammatory mRNA Profiles With Early Outcomes of Thoracic and Abdominal Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00531921
• Other study ID #: DAIT CTOT-03
• Status: Completed
• Phase: N/A
• First received: September 18, 2007
• Last updated: June 3, 2013
• Start date: September 2007
• Est. completion date: August 2011

Study information

• Verified date: June 2013
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

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.

Description:

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:

• Heart: Participants will undergo a heart biopsy that is part of standard clinical care following a heart transplant. An echocardiogram and an electrocardiogram will occur at most visits.

• Kidney: Renal biopsies will be performed 1 hour after reperfusion at the time of surgery. Urine collection will occur at most visits.

• Liver: Liver biopsies will be performed at the time of procurement and within 1 hour of reperfusion.

• Lung: Participants will undergo bronchoalveolar lavage that is part of standard clinical care following a lung transplant. A chest x-ray, an arterial blood gas test, a pulmonary function test, and 6-minute walking test will occur at some visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 313
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 70 Years

Eligibility

Inclusion Criteria for all participants:

• Received single lung, heart, kidney, or liver transplant

• Specimens of donor tissues have been collected

• Parent or guardian willing to provide informed consent, if applicable

Inclusion Criteria for Kidney or Liver Transplant Participants:

• 70 years old or younger

Inclusion Criteria for Heart or Lung Transplant Participants:

• Between 16 and 70 years old

Exclusion Criteria for All Participants:

• Previous solid organ transplant

• Need for combined organ transplant

• HIV or hepatitis C virus infection

• Recipient of an organ from a hepatitis C virus-infected donor

• Clinical evidence of systemic bacterial infection in the recipient at the time of transplantation

• Living donor transplant recipient of either a kidney, liver, or lung

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Heart Transplantation
• Kidney Transplantation
• Liver Transplantation
• Lung Transplantation

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital (kidney and liver)	Chicago	Illinois
United States	Cornell University Medical College (kidney)	Ithaca	New York
United States	University of Wisconsin (heart and lung)	Madison	Wisconsin
United States	Columbia University (lung and liver)	New York	New York
United States	University of Pennsylvania (heart, kidney, liver, lung)	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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 — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Kaplan B, Srinivas TR, Meier-Kriesche HU. Factors associated with long-term renal allograft survival. Ther Drug Monit. 2002 Feb;24(1):36-9. Review. — View Citation

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. Review. — View Citation

Reding R, Gras J, Truong DQ, Wieërs G, Latinne D. The immunological monitoring of alloreactive responses in liver transplant recipients: a review. Liver Transpl. 2006 Mar;12(3):373-83. Review. — View Citation

Zheng XX, Sánchez-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No

External Links

•   Click here for the Clinical Trials in Organ Transplantation (CTOT) public Web site