Proteogenomic Biomarker Panels in a Serial Blood & Urine Monitoring Study of Kidney Transplant Recipients

Kidney Transplantation Clinical Trial

— PROGENI-KI  

Official title:

Discovery and Validation of Proteogenomic Biomarker Panels in a Prospective Serial Blood & Urine Monitoring Study of Kidney Transplant Recipients - Transplant Proteogenomics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01289717
• Other study ID #: DAIT CTOT-08
• Status: Completed
• Phase: N/A
• First received: February 2, 2011
• Last updated: August 10, 2017
• Start date: March 2011
• Est. completion date: June 2016

Study information

• Verified date: August 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Transplant
• Kidney Transplantation

Locations

Country	Name	City	State
United States	Medical University of South Carolina, Division of Transplant	Charleston	South Carolina
United States	Northwestern University, Feinberg School of Medicine, Division of Organ Transplantation	Chicago	Illinois
United States	The Cleveland Clinic	Cleveland	Ohio
United States	The Scripps Research Institute, Scripps Center for Organ and Cell Transplantation,	La Jolla	California
United States	Mayo Clinic, Division of Nephrology	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Clinical Trials in Organ Transplantation

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. Epub 2007 Sep 14. — View Citation

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. — View Citation

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, Abeca — View Citation

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. — View Citation

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. — View Citation

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. Epub 2007 Feb 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		12 and 24 months
Secondary	Incidence of Death		Baseline to month 24
Secondary	Incidence of Graft Loss		Baseline to month 24
Secondary	Incidence of Opportunistic infections		Baseline to month 24
Secondary	Incidence of BKV, CMV, and EBV Infection		Baseline to month 24
Secondary	Incidence of Treated Urinary Tract Infection		Baseline to month 24
Secondary	Incidence of Malignancy		Baseline to month 24
Secondary	Changes that Occur in Blood, Urine, and Kidney Tissue Gene Expression Signature		Month 1 to month 24
Secondary	Changes in Plasma Protein Expression Profile		Month 1 to month 24
Secondary	Changes in Urine Protein Expression Profile		Month 1 to month 24
Secondary	Changes in Blood MicroRNA Expression Profile		Month 1 to month 24
Secondary	Evolution of Gene and Protein Expression Profiles During Response to Therapy for AR		Month 1 to month 24
Secondary	Evolution of Gene and Protein Expression Profiles During Progression or Regression of CAN/IFTA on Protocol Biopsies		Month 1 to month 24

External Links

•   Clinical Trials in Organ Transplantation (CTOT)
•   National Institutes of Allergy and Infectious Diseases (NIAID)