Proteogenomic Monitoring and Assessment of Liver Transplant Recipients

Hepatitis C Clinical Trial

— "Mini-Liver"  

Official title:

Proteogenomic Monitoring and Assessment of Liver Transplant Recipients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01644903
• Other study ID #: STU 26737
• Status: Recruiting
• Start date: April 2010
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Northwestern University
• Contact: Misael Villegas, BA
• Email: misael.villegas[@]northwestern.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is being done to test blood, urine and tissue samples to see if this can help decide if CKD (Chronic Kidney Disease), AR (Acute Rejection) and HCV (Hepatitis C Virus) can be identified in its early stages. CKD damage to the kidneys, AR and HCV all lower the body's ability to function properly. Early detection of these conditions could assist with successful treatment and possibly lead to less repeat organ transplants.

Description:

With the advent of more sensitive molecular techniques, biomarkers of kidney transplant rejection have been proposed that are potentially much more sensitive, specific and rapidly testable than conventional predictors of graft function such as GFR or tissue biopsies. Some of the early biomarkers during this evolution were the Cytotoxic T-cell (CTL) transcripts like perforin, granzyme B and fas ligand 11-13 for acute rejection. In the case of CAN/IFTA and CKD the molecular mechanisms and testable biomarkers also remain unclear. A few studies have reported the involvement of TGF-beta, extracellular matrix proteins like fibronectin and thrombopondin and tissue inhibitors of metalloproteins (TIMPs) as being upregulated in patients with Chronic Allograft Nephropathy (CAN/IFTA). Most of these studies were done in kidney transplant biopsies and the challenge of testing their expression and correlation in PBL as a minimally invasive tool was only addressed in a few studies. Another limitation of these first studies was the lack of the power to profile genes globally. To this end the advent of DNA microarrays has brought about a quantum leap in the ability to profile thousands of genes simultaneously. Thus far, microarray analysis has been reported in kidney transplant studies implicating gene signatures for acute rejection in transplant biopsies as well as for the first time by us in peripheral blood. To our knowledge only two studies have tried to profile CAN/IFTA in peripheral blood. A recent study attempted to validate three genes that were derived from a microarray analysis of kidney biopsies using RT-qPCR. All three genes were significantly differentially expressed in urine but not in PBL. Another study using microarrays showed that among a panel of 49 peripheral blood genes that were purported to distinguish "operational tolerance" in kidney rejection, 33 genes could also distinguish "chronic rejection" with 86% specificity.

Most of the studies in the literature, including our own, as well as our more recent unpublished peripheral blood gene expression studies of AR and CAN/IFTA reveal clear molecular signatures for both these forms of transplant outcomes. In sum, these data establish a first proof of concept that peripheral blood gene expression profiling can be used to develop markers of kidney allograft rejection and chronic kidney injury.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male and female recipients of all races, =18 years of age.

2. Patients undergoing primary or subsequent living or deceased donor liver transplantation.

3. Subject and/or guardian must be able to provide informed consent.

4. Subject and/or guardian must be able to comply with the study protocol.

Exclusion Criteria:

1. Inability or unwillingness of a participant and/or guardian to provide informed consent.

Related Conditions & MeSH terms

• Acute Rejection
• Chronic Kidney Disease
• Hepatitis C
• Kidney Diseases
• Liver Transplant
• Renal Insufficiency, Chronic

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	The Scripps Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proteogenomic Biomarkers for CKD, AR and HCV	To validate specific proteogenomic biomarker panels for CKD and AR (and HCV) in a prospective serial blood and urine monitoring study of liver transplant recipients	At time of liver biopsy