Molecular Biomarkers in Renal Transplantation Via TruGraf® Test

Kidney Transplant Rejection Clinical Trial

Official title:

Molecular Biomarkers in Renal Transplantation Via TruGraf® Test

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04398498
• Other study ID #: TGRP05-US005
• Status: Enrolling by invitation
• Start date: April 13, 2020
• Est. completion date: November 30, 2022

Study information

• Verified date: August 2021
• Source: Transplant Genomics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The TruGraf® test is a non-invasive blood test that measures molecular gene expression profiles associated with clinical conditions previously only diagnosed by biopsy in kidney transplant recipients. The results of the TruGraf test provide additional information about the adequacy of immunosuppression and may be used to support decisions in patient management.

Description:

This is a single-center, prospective, randomized study to evaluate clinical utility of TruGraf testing in patients with the following characteristics:1.Stable serum creatinine: current serum creatinine <2.3 mg/dl, <20% increase compare to the average of the previous 3 serum creatinine levels2.Kidney transplant patients who are:•more than 60 days post-transplant will be included in this study (Study A) •more than 2-yearspost-transplant but less than 5 years post-transplant (>24 months but < 60 months) will be included in this study (Study B) Scripps will enroll subjects who are post-transplant and are undergoing routine management. In Study A, patients will receive testing eight times: Month 2 (at time of surveillance biopsy) 6(at time of surveillance biopsy), 9, 12(at time of surveillance biopsy), 15, 18, 21 and 24(at time of surveillance biopsy) (plus or minus two weeks). Results of the genomic analysis will be considered in determining patient treatment plans and as a molecular guide to perform a surveillance biopsy. Clinical data elements using the Scripps EHR and cost of care will be collected for all subjects. In Study B, patients who are at least 2 years post transplant up to 5 years post-transplant will receive testing 8 times: Months 3 ,6, 9, 12, 15, 18, 21 and 24 (plus or minus two weeks)from the time of enrollment into the study. Results of the genomic analysis will be considered in determining patient treatment plans and whether any change is needed, such as whether to perform a surveillance biopsy. Clinical data elements using the Scripps EHR and cost of care will be collected for all subjects. We expect Study A to be completed 24-30months and Study B to be completed in 24-30 months.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 50
• Est. completion date: November 30, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Recipient of a primary or subsequent deceased-donor or living donor kidney transplantation.

• Stable serum creatinine (current serum creatinine <2.3 mg/dl, <20% increase compared to the average of the previous 3 serum creatinine levels).

• Kidney transplant patients who are: > 60 days post-transplant (Cohort A); > 2-years post-transplant (Cohort B)

Exclusion Criteria:

• Need for combined organ transplantation with an extra-renal organ and/or islet cell transplant.

• Recipients of previous non-renal solid organ and/or islet cell transplantation.

• Infection with HIV.

• Infection with BK.

• Patients that have nephritic proteinuria (urine protein >3 gm/day).

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

Diagnostic Test:
• Diagnostic Test: TruGraf® Testing
5 mL collection PAXgene blood sample

Locations

Country	Name	City	State
United States	Scripps Clinic	La Jolla	California

Sponsors (2)

Lead Sponsor	Collaborator
Transplant Genomics, Inc.	Scripps Health

Country where clinical trial is conducted

United States, 

References & Publications (15)

Heilman RL, Devarapalli Y, Chakkera HA, Mekeel KL, Moss AA, Mulligan DC, Mazur MJ, Hamawi K, Williams JW, Reddy KS. Impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy in kidney transplant recipients. Am J Transplant. 2010 Mar;10(3):563-70. doi: 10.1111/j.1600-6143.2009.02966.x. Epub 2010 Feb 1. — View Citation

Kirk AD, Jacobson LM, Heisey DM, Radke NF, Pirsch JD, Sollinger HW. Clinically stable human renal allografts contain histological and RNA-based findings that correlate with deteriorating graft function. Transplantation. 1999 Nov 27;68(10):1578-82. — View Citation

Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United States: a critical reappraisal. Am J Transplant. 2011 Mar;11(3):450-62. doi: 10.1111/j.1600-6143.2010.03283.x. Epub 2010 Oct 25. — View Citation

Legendre C, Thervet E, Skhiri H, Mamzer-Bruneel MF, Cantarovich F, Noël LH, Kreis H. Histologic features of chronic allograft nephropathy revealed by protocol biopsies in kidney transplant recipients. Transplantation. 1998 Jun 15;65(11):1506-9. — View Citation

Matas AJ, Gillingham KJ, Humar A, Kandaswamy R, Sutherland DE, Payne WD, Dunn TB, Najarian JS. 2202 kidney transplant recipients with 10 years of graft function: what happens next? Am J Transplant. 2008 Nov;8(11):2410-9. doi: 10.1111/j.1600-6143.2008.02414.x. — View Citation

Matas AJ, Smith JM, Skeans MA, Thompson B, Gustafson SK, Stewart DE, Cherikh WS, Wainright JL, Boyle G, Snyder JJ, Israni AK, Kasiske BL. OPTN/SRTR 2013 Annual Data Report: kidney. Am J Transplant. 2015 Jan;15 Suppl 2:1-34. doi: 10.1111/ajt.13195. — View Citation

Montgomery RA. One kidney for life. Am J Transplant. 2014 Jul;14(7):1473-4. doi: 10.1111/ajt.12772. Epub 2014 May 9. — View Citation

Moreso F, Ibernon M, Gomà M, Carrera M, Fulladosa X, Hueso M, Gil-Vernet S, Cruzado JM, Torras J, Grinyó JM, Serón D. Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss. Am J Transplant. 2006 Apr;6(4):747-52. — View Citation

Nankivell BJ, Chapman JR. The significance of subclinical rejection and the value of protocol biopsies. Am J Transplant. 2006 Sep;6(9):2006-12. Epub 2006 Jun 22. Review. — View Citation

Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Yamaguchi Y, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999 Feb;55(2):713-23. — View Citation

Rana A, Gruessner A, Agopian VG, Khalpey Z, Riaz IB, Kaplan B, Halazun KJ, Busuttil RW, Gruessner RW. Survival benefit of solid-organ transplant in the United States. JAMA Surg. 2015 Mar 1;150(3):252-9. doi: 10.1001/jamasurg.2014.2038. — View Citation

Rush D, Nickerson P, Gough J, McKenna R, Grimm P, Cheang M, Trpkov K, Solez K, Jeffery J. Beneficial effects of treatment of early subclinical rejection: a randomized study. J Am Soc Nephrol. 1998 Nov;9(11):2129-34. — View Citation

Rush DN, Henry SF, Jeffery JR, Schroeder TJ, Gough J. Histological findings in early routine biopsies of stable renal allograft recipients. Transplantation. 1994 Jan;57(2):208-11. — View Citation

Serón D, Moreso F. Protocol biopsies in renal transplantation: prognostic value of structural monitoring. Kidney Int. 2007 Sep;72(6):690-7. Epub 2007 Jun 27. Review. — View Citation

Waldmann H. Drug minimization in transplantation: an opinion. Curr Opin Organ Transplant. 2014 Aug;19(4):331-3. doi: 10.1097/MOT.0000000000000099. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort A: Percent or total number of patients who physicians decided could forego a surveillance biopsy due to TruGraf results		12 months post-transplant
Primary	Cohort A: Percent or total number of patients who physicians decided could forego a surveillance biopsy due to TruGraf results		24 months post-transplant
Primary	Cohort A: Correlation of TruGraf test results with surveillance biopsy		2 years
Primary	Cohort A and B: Banff pathology	Banff pathology will be assessed and compared to TruGraf results.	2 years
Primary	Cohort A and B: Renal graft function	Renal graft function will be assessed by measuring Estimated Glomerular Filtration Rate (eGFR).	2 years
Primary	Cohort A and B: Renal graft function	Renal graft function will be assessed by measuring serum creatinine (sCr) levels.	2 years
Primary	Cohort A and B: Cost of patient care	The cost of patient care will be evaluated by measuring the total health care spending for health care services provided during the study period.	2 years
Secondary	Incidence of death		2 years
Secondary	Incidence of graft loss		2 years

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