Genomics of Chronic Renal Allograft Rejection (The GoCAR Study)

This study has been completed.

Sponsor:

ClinicalTrials.gov Identifier:

NCT00611702

First Posted: February 11, 2008

Last Update Posted: May 14, 2015

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

Doctors have had success preventing certain types of kidney transplant rejection by suppressing the immune system. However, an individual's genetic make-up and the strength of an immune response to a transplant may also determine whether a transplanted organ is rejected. The purpose of this study is to look at the genetic profile and immune response of people who have had kidney transplants and to correlate the findings with kidney transplant rejection episodes. Donor genetic profiles will also be studied and correlated with the recipient's information.

Condition	Intervention
Kidney Transplantation	Procedure: Kidney biopsy


Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Genomics of Chronic Renal Allograft Rejection

Resource links provided by NLM:

MedlinePlus related topics: Biopsy

U.S. FDA Resources

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

Primary Outcome Measures:

Correlation of chronic rejection with patterns and intensity of recipient alloreactivity [ Time Frame: Throughout study ]
Correlation of chronic rejection with recipient gene expression profiles [ Time Frame: Throughout study ]
Correlation of chronic rejection with polymorphic variants of specific susceptibility genes in donor and recipient [ Time Frame: Throughout study ]

Secondary Outcome Measures:

Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with patterns and intensity of recipient alloreactivity [ Time Frame: Throughout study ]
Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with recipient gene expression profiles [ Time Frame: Throughout study ]
Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy with polymorphic variants of specific susceptibility genes in donor and recipient [ Time Frame: Throughout study ]
Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy with chronic rejection [ Time Frame: Throughout study ]
Correlation of the development of donor-specific antibodies after transplant and/or the presence of C4d staining of peritubular basement membranes on renal biopsy allograft dysfunction as defined by the protocol [ Time Frame: Throughout study ]

Biospecimen Retention: Samples With DNA

Blood from both kidney donor and recipient and transplant kidney biopsy samples


Enrollment:	588
Study Start Date:	June 2008
Study Completion Date:	July 2013
Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Intervention Details:

Kidney biopsy (recipients only) will be obtained for RT-PCR, microarray analyses and histology.

Detailed Description:

New immunosuppressive drugs have improved short-term transplant survival but have not affected long-term transplant survival. Rejection is caused by both immunological and non-immunological factors from both the donor and the recipient. Although the exact cause of chronic rejection is not known, it is associated with the presence of C4d, a degradation product of the antibody response cascade, and the presence of circulating donor-specific antibodies (DSAs). The purpose of this study is to determine the role of cell- and antibody-mediated responses in chronic rejection of transplants, to determine the gene expression profile associated with the development of chronic rejection, and to determine whether variants of specific genes cause susceptibility to rejection.

This is an observational study of people who will be receiving kidney transplants and participants will be followed for 2 years. Study visits for kidney transplant recipients will occur at study entry and at months 3, 6, 12, 18, and 24 after transplant. At these visits, adverse event assessment, rejection assessment, medication history questionnaire, and blood collection will occur. At some visits, a physical exam and a kidney biopsy will occur. Blood will also be collected from living kidney donors at the time of donation if both donor and recipient agree to be in the study. This study will be take place at 4 clinical sites: Mount Sinai School of Medicine, University of Wisconsin-Madison, Westmead Hospital, and Northwestern Memorial Hospital. Brigham and Women's Hospital and Massachusetts General Hospital will also participate in the study as central laboratories.

Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Individuals receiving a kidney transplant and individuals who are donating a kidney

Criteria

Inclusion Criteria:

Kidney transplant candidates from living or deceased donors
Male or female, ages 18-75 years
Subject must be able to understand and provide written informed consent
Living Donors - Recipient also consents to participate in the study

Exclusion Criteria:

Presence of Donor Specific Antibodies in living donor recipients prior to transplantation OR positive cross match according to site-specific technique in cadaveric donor recipients
Recipients of multiple organ transplants, with the exception of kidney/pancreas transplants.
Inability or unwillingness to comply with the study protocol.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00611702

Locations


United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, New York
Mt. Sinai School of Medicine
New York, New York, United States, 10029
United States, Wisconsin
University of Wisconsin-Madison
Madison, Wisconsin, United States, 53706
Australia, New South Wales
Westmead Hospital
Sydney, New South Wales, Australia, 2145

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Principal Investigator:	Barbara T. Murphy, MD	Division of Nephrology, Mt. Sinai School of Medicine

More Information

Additional Information:

National Institute of Allergy and Infectious Diseases (NIAID) This link exits the ClinicalTrials.gov site

Publications:

Vitalone MJ, O'Connell PJ, Wavamunno M, Fung CL, Chapman JR, Nankivell BJ. Transcriptome changes of chronic tubulointerstitial damage in early kidney transplantation. Transplantation. 2010 Mar 15;89(5):537-47. doi: 10.1097/TP.0b013e3181ca7389.

Vitalone MJ, O'Connell PJ, Jimenez-Vera E, Yuksel A, Wavamunno M, Fung CL, Chapman JR, Nankivell BJ. Epithelial-to-mesenchymal transition in early transplant tubulointerstitial damage. J Am Soc Nephrol. 2008 Aug;19(8):1571-83. doi: 10.1681/ASN.2007050580. Epub 2008 May 14.

Dinavahi R, George A, Tretin A, Akalin E, Ames S, Bromberg JS, Deboccardo G, Dipaola N, Lerner SM, Mehrotra A, Murphy BT, Nadasdy T, Paz-Artal E, Salomon DR, Schröppel B, Sehgal V, Sachidanandam R, Heeger PS. Antibodies reactive to non-HLA antigens in transplant glomerulopathy. J Am Soc Nephrol. 2011 Jun;22(6):1168-78. doi: 10.1681/ASN.2010111183. Epub 2011 May 12.

Krüger B, Krick S, Dhillon N, Lerner SM, Ames S, Bromberg JS, Lin M, Walsh L, Vella J, Fischereder M, Krämer BK, Colvin RB, Heeger PS, Murphy BT, Schröppel B. Donor Toll-like receptor 4 contributes to ischemia and reperfusion injury following human kidney transplantation. Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3390-5. doi: 10.1073/pnas.0810169106. Epub 2009 Feb 13.

Wavamunno MD, O'Connell PJ, Vitalone M, Fung CL, Allen RD, Chapman JR, Nankivell BJ. Transplant glomerulopathy: ultrastructural abnormalities occur early in longitudinal analysis of protocol biopsies. Am J Transplant. 2007 Dec;7(12):2757-68. Epub 2007 Oct 6.

Gurkan S, Luan Y, Dhillon N, Allam SR, Montague T, Bromberg JS, Ames S, Lerner S, Ebcioglu Z, Nair V, Dinavahi R, Sehgal V, Heeger P, Schroppel B, Murphy B. Immune reconstitution following rabbit antithymocyte globulin. Am J Transplant. 2010 Sep;10(9):2132-2141. doi: 10.1111/j.1600-6143.2010.03210.x. Erratum in: Am J Transplant. 2010 Dec;10(12):2728.

Farris AB, Adams CD, Brousaides N, Della Pelle PA, Collins AB, Moradi E, Smith RN, Grimm PC, Colvin RB. Morphometric and visual evaluation of fibrosis in renal biopsies. J Am Soc Nephrol. 2011 Jan;22(1):176-86. doi: 10.1681/ASN.2009091005. Epub 2010 Nov 29.

Schröppel B, Krüger B, Walsh L, Yeung M, Harris S, Garrison K, Himmelfarb J, Lerner SM, Bromberg JS, Zhang PL, Bonventre JV, Wang Z, Farris AB, Colvin RB, Murphy BT, Vella JP. Tubular expression of KIM-1 does not predict delayed function after transplantation. J Am Soc Nephrol. 2010 Mar;21(3):536-42. doi: 10.1681/ASN.2009040390. Epub 2009 Dec 17.

Luan Y, Mosheir E, Menon MC, Wilson D, Woytovich C, Ochando J, Murphy B. Monocytic myeloid-derived suppressor cells accumulate in renal transplant patients and mediate CD4(+) Foxp3(+) Treg expansion. Am J Transplant. 2013 Dec;13(12):3123-31. doi: 10.1111/ajt.12461. Epub 2013 Sep 18.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

O'Connell PJ, Zhang W, Menon MC, Yi Z, Schröppel B, Gallon L, Luan Y, Rosales IA, Ge Y, Losic B, Xi C, Woytovich C, Keung KL, Wei C, Greene I, Overbey J, Bagiella E, Najafian N, Samaniego M, Djamali A, Alexander SI, Nankivell BJ, Chapman JR, Smith RN, Colvin R, Murphy B. Biopsy transcriptome expression profiling to identify kidney transplants at risk of chronic injury: a multicentre, prospective study. Lancet. 2016 Sep 3;388(10048):983-93. doi: 10.1016/S0140-6736(16)30826-1. Epub 2016 Jul 22.


Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00611702 History of Changes
Other Study ID Numbers:	DAIT GTCRP-01
First Submitted:	February 7, 2008
First Posted:	February 11, 2008
Last Update Posted:	May 14, 2015
Last Verified:	May 2015

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):


ELISPOT RT-PCR Luminex Genomics

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