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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00531921
First received: September 18, 2007
Last updated: June 3, 2013
Last verified: June 2013
  Purpose

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.


Condition
Heart Transplantation
Kidney Transplantation
Liver Transplantation
Lung Transplantation

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Correlation of Donor Proinflammatory mRNA Profiles With Early Outcomes of Thoracic and Abdominal Transplantation

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Association between proinflammatory mRNA expression in donor samples and subsequent development of early organ dysfunction in the immediate period following transplantation [ Time Frame: Within first 7 days after transplant ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 12 months after transplant ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood and tissue samples to evaluate the heart, kidney, liver, and lung


Enrollment: 313
Study Start Date: September 2007
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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.
  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Transplant patients evaluated for the association between proinflammatory mRNA expression from donor samples and subsequent development of early organ dysfunction

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531921

Locations
United States, Illinois
Northwestern Memorial Hospital (kidney and liver)
Chicago, Illinois, United States, 60611
United States, New York
Cornell University Medical College (kidney)
Ithaca, New York, United States, 14850
Columbia University (lung and liver)
New York, New York, United States, 10032
United States, Pennsylvania
University of Pennsylvania (heart, kidney, liver, lung)
Philadelphia, Pennsylvania, United States, 19104
United States, Wisconsin
University of Wisconsin (heart and lung)
Madison, Wisconsin, United States, 53706
Sponsors and Collaborators
Investigators
Principal Investigator: Abraham Shaked, MD, PhD University of Pennsylvania Medical Center
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00531921     History of Changes
Other Study ID Numbers: DAIT CTOT-03
Study First Received: September 18, 2007
Last Updated: June 3, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Heart Diseases
Kidney Diseases
Liver Diseases
Liver Failure
Lung Diseases
Transplant
Transplantation, Homologous
Rejection
Kidney Failure

ClinicalTrials.gov processed this record on September 30, 2014