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Kidney TransplantationNCT00611702

Genomics of Chronic Renal Allograft Rejection (The GoCAR Study)

An observational study of Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Kidney Transplantation
What is being tested?
Kidney biopsy
Type of treatment
Surgery or procedure
How many people
588 participants
Where
5 sitesin 2 countries
Study dates
Jun 2008to Jul 2013
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Individuals receiving a kidney transplant and individuals who are donating a kidney

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

5 sites in 2 countries.

5 sites in 2 countries

United States4 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Northwestern Memorial Hospital

    Chicago, Illinois, 60611

  • University of Wisconsin-Madison

    Madison, Wisconsin, 53706

  • Mt. Sinai School of Medicine

    New York, New York, 10029

Other trials in United States

Australia1 site

  • Westmead Hospital

    Sydney, New South Wales, 2145

Other trials in Australia

About this study

Official title: Genomics of Chronic Renal Allograft Rejection

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.

Read the 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.

Being tested
Kidney biopsy
Keywords
ELISPOT, RT-PCR, Luminex, Genomics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Kidney biopsyProcedure or surgery

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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Correlation of chronic rejection with patterns and intensity of recipient alloreactivity

    Measured: Throughout study

  2. Correlation of chronic rejection with recipient gene expression profiles

    Measured: Throughout study

  3. Correlation of chronic rejection with polymorphic variants of specific susceptibility genes in donor and recipient

    Measured: Throughout study

Secondary outcomes (5)

  1. Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with patterns and intensity of recipient alloreactivity

    Measured: Throughout study

  2. Correlation of the development of donor specific antibodies after transplant and/or the presence of C4d staining with recipient gene expression profiles

    Measured: Throughout study

  3. 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

    Measured: Throughout study

  4. 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

    Measured: Throughout study

  5. 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

    Measured: Throughout study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Feb 2008 (estimated)
  2. Study startJun 2008
  3. Primary completionJul 2013
  4. Study completionJul 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
588 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00611702
Sponsor's protocol ID
DAIT GTCRP-01
Status last verified
May 2015
First submitted
7 Feb 2008
Last updated
14 May 2015
Results posted
No
Data monitoring committee
Yes

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.

    PubMed 20147884

  • 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.

    PubMed 18480317

  • 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, Schroppel 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.

    PubMed 21566057

  • Kruger B, Krick S, Dhillon N, Lerner SM, Ames S, Bromberg JS, Lin M, Walsh L, Vella J, Fischereder M, Kramer BK, Colvin RB, Heeger PS, Murphy BT, Schroppel 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.

    PubMed 19218437

  • 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. doi: 10.1111/j.1600-6143.2007.01995.x. Epub 2007 Oct 6.

    PubMed 17924997

  • 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.

    PubMed 20883548

  • 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.

    PubMed 21115619

  • Schroppel B, Kruger 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.

    PubMed 20019169

  • 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.

    PubMed 24103111

  • O'Connell PJ, Zhang W, Menon MC, Yi Z, Schroppel 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.

    PubMed 27452608

Questions about this trial

What is this clinical trial studying?

An observational study of Kidney Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Correlation of chronic rejection with patterns and intensity of recipient alloreactivity (time frame: Throughout study). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00611702, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2015.

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