TruGraf and TRAC In Pediatrics Study

Kidney Transplant Rejection Clinical Trial

— TTIPS  

Official title:

The Role of TruGraf® to Optimize Outcomes in Pediatric Renal Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05335538
• Other study ID #: TGRP08
• Status: Recruiting
• Start date: November 30, 2021
• Est. completion date: March 1, 2023

Study information

• Verified date: August 2021
• Source: Transplant Genomics, Inc.
• Contact: Cortney Miller, PhD
• Phone: 5107753326
• Email: cortneymiller[@]eurofins-tgi.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a pilot 3 center prospective study of pediatric renal kidney recipients undergoing protocol biopsies examining the performance of the TruGraf gene expression test in children and adolescents.

Description:

In pediatric renal transplant recipients, subclinical rejection in protocol biopsies is associated with a significantly increased incidence of acute rejection and/or allograft loss at 5 years post-transplant. Currently, TruGraf is the only noninvasive test designed and validated in adult kidney transplant recipients for use in ruling out silent subacute rejection in that has been approved by Medicare as an alternative to surveillance biopsies. The first step to the use of TruGraf in pediatrics is to perform a validation study in children and adolescents. Specifically, if validated in children and adolescents, a TruGraf result would enable a pediatric transplant physician to identify patients in whom no intervention is necessary without the need of a protocol biopsy. Therefore the aim of this study is to examine the concordance between the results of the TruGraf tests and protocol biopsies taken from stable pediatric renal transplant patients concurrently.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: March 1, 2023
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

Inclusion Criteria:

• Patients aged 1-= 18 years and recipients of either living or deceased donor transplants Undergoing a protocol biopsy at either 3, 6, 12, 24 or 36 months
• Serum creatinine at the time of the clinic visit prior to the scheduled biopsy within 30% of a baseline calculated as the mean of the recipient's last 3 serum creatinine levels
• Serum creatinine level at the time of protocol biopsy = 1.7 mg/dl.
• Patient receiving immunosuppression with a calcineurin inhibitor (either tacrolimus or cyclosporine) and/or an antimetabolite (either mycophenolate mofetil, mycophenolic acid EC or azathioprine) and/or an mTOR inhibitor (either sirolimus or everolimus) and/or corticosteroids.
• Absence of any systemic or urinary bacterial, viral or fungal infection
• Absence of significant BK viremia (as determined by the laboratory where the determination is run) at the time of the last clinical determination and at the time of the protocol biopsy
• Parents or guardians are capable of reading and understanding the Informed Consent document and willing to participate; if appropriate, patient is also able to understand the Informed Consent. If patient is older than 13 years, patient should be able to give Assent as written on Assent Form.
• For females of child-bearing age, a negative pregnancy test within 6 weeks of the protocol biopsy.

Exclusion Criteria:

• Refusal to undergo clinical standard-of-care protocol biopsy by either parent/guardian or patient.
• Inability to obtain adequate tissue on protocol biopsy
• Current participation in another interventional research study; patients who have completed the drug in another interventional study are eligible if they meet all other inclusion criteria.
• Serum creatinine at the clinic visit prior to the biopsy is > 30% of a baseline calculated as the mean of the recipient's last 3 serum creatinine levels.
• Serum creatinine at the time of the protocol biopsy = 1.8 mg/dl. If the patient had a baseline < 1.8, and the creatinine on the day of biopsy is = 1.8, at the discretion of the PI, the patient will be instructed to hydrate for 4 days and a serum creatinine will be obtained at that time. This is standard clinical practice. If the creatinine returns to the baseline (i.e., = 30%) range, the patient will be classified as having stable renal function, while if the patient's serum creatinine does not return to the = 30% range, he/she will be classified as having renal dysfunction
• Patients who, in the estimation of the investigator, are undergoing "for-cause" biopsies.
• Presence of any current and active bacterial, viral or fungal infection
• Presence of BK viremia judged to be significant by the site PI.
• Presence of BK nephropathy
• History of PTLD or malignancy
• Parents / guardians do not understand Informed Consent and / or are unwilling to participate; patient, if of appropriate age, is unwilling to participate
• Patients manifesting recurrent disease in their transplant (such as FSGS/nephrotic syndrome, C3 Glomeruopathy, MPGN, hyperoxaluria)
• Abnormal proteinuria as determined by a urinary protein: creatinine ratio of >1.
• Recipients of multi-organ transplants.

Related Conditions & MeSH terms

• Kidney Transplant Rejection

Intervention

Diagnostic Test:
• Patients monitored with TruGraf and TRAC testing
This is an observational study there are no protocol mandated interventions. TruGraf and TRAC results will be utilized in conjunction with standard of care assessments to determine patient management.

Locations

Country	Name	City	State
Canada	British Columbia Children's Hospital	Vancouver
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	UCLA Mattel Children's Hospital	Los Angeles	California

Sponsors (4)

Lead Sponsor	Collaborator
Transplant Genomics, Inc.	University of Alabama at Birmingham, University of British Columbia, University of California, Los Angeles

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (62)

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Ho J, Rush DN, Karpinski M, Storsley L, Gibson IW, Bestland J, Gao A, Stefura W, HayGlass KT, Nickerson PW. Validation of urinary CXCL10 as a marker of borderline, subclinical, and clinical tubulitis. Transplantation. 2011 Oct 27;92(8):878-82. doi: 10.1097/TP.0b013e31822d4de1. — View Citation

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Kurian SM, Velazquez E, Thompson R, Whisenant T, Rose S, Riley N, Harrison F, Gelbart T, Friedewald JJ, Charette J, Brietigam S, Peysakhovich J, First MR, Abecassis MM, Salomon DR. Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform. Am J Transplant. 2017 Aug;17(8):2103-2116. doi: 10.1111/ajt.14224. Epub 2017 Apr 3. — View Citation

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United States Renal Data System 2018 Annual Data Report Volume 2 ESRD Chapter 5

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* Note: There are 62 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concordance of Biomarkers with protocol biopsy	Examination of the concordance between the results of the TruGraf tests and protocol biopsies taken from stable pediatric renal transplant concurrently.	1 year
Secondary	Concordance between the results of the TruGraf test and the histological finding of borderline changes vs. TCMR vs. AMR.	Separately examine the concordance between the results of the TruGraf test and the histological finding of borderline changes vs. TCMR vs. AMR.	1 year
Secondary	Compare TruGraf results in patients = 11 years old vs = 12 years old	Compare the agreement between protocol biopsies and TruGraf results in patients = 11 years old vs = 12 years old	1 year
Secondary	Relationship between de novo DSA, a normal protocol biopsy and the TruGraf result.	Assess the relationship, if any, between the appearance of de novo DSA, a normal protocol transplant biopsy and the TruGraf result.	1 year
Secondary	Examine TruGraf results and the %CV tacrolimus levels- index of medication nonadherence.	Examine the relationship between the TruGraf results and the %CV tacrolimus levels as an index of medication nonadherence.	1 year
Secondary	Relationship between urinary CXCL10 and subclinical rejection affecting the predictive value of TruGraf.	Examine the relationship between urinary CXCL10 and subclinical rejection in this patient cohort to examine whether it improves the performance metrics by improving the negative or positive predictive of TruGraf.	1 year
Secondary	Examine relationship between ddcfDNA and subclinical rejection	Examine the relationship between ddcfDNA and subclinical rejection in this patient cohort	1 year