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

NCT ID: NCT00531921

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 313 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2011-08-31

Brief 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.

Detailed 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.

Conditions

Heart Transplantation; Kidney Transplantation; Liver Transplantation; Lung Transplantation

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Kidney transplants

patients from 5 specific sites

No interventions assigned to this group

Liver transplants

patients from 5 specific sites

No interventions assigned to this group

Heart transplants

patients from 5 specific sites

No interventions assigned to this group

Lung transplants

patients from 5 specific sites

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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

• 70 years old or younger

• Between 16 and 70 years old

Exclusion Criteria

• 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

• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Abraham Shaked, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania Medical Center

Locations

Northwestern Memorial Hospital (kidney and liver)

Chicago, Illinois, United States

Cornell University Medical College (kidney)

Ithaca, New York, United States

Columbia University (lung and liver)

New York, New York, United States

University of Pennsylvania (heart, kidney, liver, lung)

Philadelphia, Pennsylvania, United States

University of Wisconsin (heart and lung)

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 11867677 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9626898 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17168794 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11805720 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17202291 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16498661 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14563315 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23710539 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 20677285 (View on PubMed)

Related Links

http://www.ctotstudies.org

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

Other Identifiers

DAIT CTOT-03

Identifier Type: -

Identifier Source: org_study_id