Proteogenomic Biomarker Panels in a Serial Blood & Urine Monitoring Study of Kidney Transplant Recipients (PROGENI-KI)

• ClinicalTrials.gov Identifier: NCT01289717
• Recruitment Status: Completed
• First Posted: February 4, 2011
• Last Update Posted: August 14, 2017
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Clinical Trials in Organ Transplantation
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

There is a need to develop blood and/or urine tests that will help to detect early signs of rejection in people who have had kidney transplant. Researchers will examine blood, urine, and tissue samples and try to identify genetic markers for certain conditions like rejection, response to therapy, and scarring of the kidney. By studying gene patterns, researchers hope to be able to diagnose these conditions earlier and improve kidney survival.

Condition or disease
Kidney Transplant; Kidney Transplantation

Detailed Description:

Kidney transplantation is a good treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it working for a long time. One field of interest is how one's cellular make-up might affect the body's immune response (body's natural defense system to illness and foreign things) to a kidney transplant. Cellular tests, like gene expression, help doctors to study a person's cellular traits. Gene expression is when information found in one's DNA is translated into RNA and eventually proteins. These components are present in each of the body's cells. In this study, researchers are trying to learn if certain changes in the RNA and proteins found in blood, urine, or transplant biopsy tissue can detect rejection before injury can occur or become too severe. The blood and urine tests will look for patterns in one's DNA (called genetic markers).

This study will follow subjects for 2 years after transplant. There will be a total of 12 study visits with additional study visits if rejection occurs. The study requires additional samples of blood, urine, and tissue to be collected during routine clinical visits and biopsies (a procedure to remove and examine a small piece of kidney tissue).

Study Design

• Study Type: Observational
• Actual Enrollment: 307 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Discovery and Validation of Proteogenomic Biomarker Panels in a Prospective Serial Blood & Urine Monitoring Study of Kidney Transplant Recipients - Transplant Proteogenomics
• Study Start Date: March 2011
• Actual Primary Completion Date: June 2016
• Actual Study Completion Date: June 2016

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Incidence of Biopsy Proven Acute Rejection (AR)-Clinical and Sub-Clinical), Chronic Allograft Nephropathy/Interstitial Fibrosis and Tubular Atrophy (CAN/IFTA), and Normal Renal Biopsy with Stable, Good Kidney Function [ Time Frame: 12 and 24 months ]

Secondary Outcome Measures :

1. Incidence of Death [ Time Frame: Baseline to month 24 ]
2. Incidence of Graft Loss [ Time Frame: Baseline to month 24 ]
3. Incidence of Opportunistic infections [ Time Frame: Baseline to month 24 ]
4. Incidence of BKV, CMV, and EBV Infection [ Time Frame: Baseline to month 24 ]
5. Incidence of Treated Urinary Tract Infection [ Time Frame: Baseline to month 24 ]
6. Incidence of Malignancy [ Time Frame: Baseline to month 24 ]
7. Changes that Occur in Blood, Urine, and Kidney Tissue Gene Expression Signature [ Time Frame: Month 1 to month 24 ]
8. Changes in Plasma Protein Expression Profile [ Time Frame: Month 1 to month 24 ]
9. Changes in Urine Protein Expression Profile [ Time Frame: Month 1 to month 24 ]
10. Changes in Blood MicroRNA Expression Profile [ Time Frame: Month 1 to month 24 ]
11. Evolution of Gene and Protein Expression Profiles During Response to Therapy for AR [ Time Frame: Month 1 to month 24 ]
12. Evolution of Gene and Protein Expression Profiles During Progression or Regression of CAN/IFTA on Protocol Biopsies [ Time Frame: Month 1 to month 24 ]

Biospecimen Retention:   Samples With DNA

Samples of blood, urine, and tissue

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Adults undergoing kidney transplantation.

Criteria

Inclusion Criteria:

• Subjects undergoing primary or subsequent deceased-donor or living donor kidney transplantation
• Subject and/or parent guardian must be able to understand and provide informed consent
• Female subjects of childbearing potential must have a negative pregnancy test within 6 weeks of study entry.

Exclusion Criteria:

• Need for combined organ transplantation with an extra-renal organ and/or islet
• Recipient of previous non-renal solid organ and/or islet cell transplantation
• Infection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV)
• Inability or unwillingness of a participant to give written informed consent or comply with study protocol
• Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic, Division of Nephrology

Phoenix, Arizona, United States, 85054

United States, California

The Scripps Research Institute, Scripps Center for Organ and Cell Transplantation,

La Jolla, California, United States, 92037

United States, Illinois

Northwestern University, Feinberg School of Medicine, Division of Organ Transplantation

Chicago, Illinois, United States, 60611

United States, Ohio

The Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, South Carolina

Medical University of South Carolina, Division of Transplant

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Clinical Trials in Organ Transplantation

Investigators

• Principal Investigator: Michael Abecassis, MD, MBA; Northwestern University
• Study Chair: John J Friedewald, MD; Northwestern University

More Information

Additional Information:

National Institutes of Allergy and Infectious Diseases (NIAID) 

Clinical Trials in Organ Transplantation (CTOT) 

Publications of Results:

Kurian SM, Williams AN, Gelbart T, Campbell D, Mondala TS, Head SR, Horvath S, Gaber L, Thompson R, Whisenant T, Lin W, Langfelder P, Robison EH, Schaffer RL, Fisher JS, Friedewald J, Flechner SM, Chan LK, Wiseman AC, Shidban H, Mendez R, Heilman R, Abecassis MM, Marsh CL, Salomon DR. Molecular classifiers for acute kidney transplant rejection in peripheral blood by whole genome gene expression profiling. Am J Transplant. 2014 May;14(5):1164-72. doi: 10.1111/ajt.12671. Epub 2014 Apr 11.

Other Publications:

Kurian SM, Heilman R, Mondala TS, Nakorchevsky A, Hewel JA, Campbell D, Robison EH, Wang L, Lin W, Gaber L, Solez K, Shidban H, Mendez R, Schaffer RL, Fisher JS, Flechner SM, Head SR, Horvath S, Yates JR, Marsh CL, Salomon DR. Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood. PLoS One. 2009 Jul 10;4(7):e6212. doi: 10.1371/journal.pone.0006212.

Brouard S, Mansfield E, Braud C, Li L, Giral M, Hsieh SC, Baeten D, Zhang M, Ashton-Chess J, Braudeau C, Hsieh F, Dupont A, Pallier A, Moreau A, Louis S, Ruiz C, Salvatierra O, Soulillou JP, Sarwal M. Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15448-53. doi: 10.1073/pnas.0705834104. Epub 2007 Sep 14.

Mas VR, Mas LA, Archer KJ, Yanek K, King AL, Gibney EM, Cotterell A, Fisher RA, Posner M, Maluf DG. Evaluation of gene panel mRNAs in urine samples of kidney transplant recipients as a non-invasive tool of graft function. Mol Med. 2007 May-Jun;13(5-6):315-24. doi: 10.2119/2007-00017.Mas.

Muthukumar T, Dadhania D, Ding R, Snopkowski C, Naqvi R, Lee JB, Hartono C, Li B, Sharma VK, Seshan SV, Kapur S, Hancock WW, Schwartz JE, Suthanthiran M. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N Engl J Med. 2005 Dec 1;353(22):2342-51. doi: 10.1056/NEJMoa051907.

Veronese F, Rotman S, Smith RN, Pelle TD, Farrell ML, Kawai T, Benedict Cosimi A, Colvin RB. Pathological and clinical correlates of FOXP3+ cells in renal allografts during acute rejection. Am J Transplant. 2007 Apr;7(4):914-22. doi: 10.1111/j.1600-6143.2006.01704.x. Epub 2007 Feb 7.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01289717
• Other Study ID Numbers: DAIT CTOT-08
• First Posted: February 4, 2011
• Last Update Posted: August 14, 2017
• Last Verified: August 2017

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

biomarkers; proteogenomic profiling; acute rejection; chronic allograft nephropathy/interstitial fibrosis and tubular atrophy