Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation

Recruiting

• Conditions: Liver Dysfunction

• Registration Number: NCT03193151
• Lead Sponsor: University of Alberta

Brief Summary

INTERLIVER is a prospective observational study of the relationship of the molecular phenotype of 300 liver transplant biopsies to the histologic phenotype and the clinical features and outcomes. A segment of a biopsy performed as standard-of-care for indications, or by center protocol, will be used for gene expression study.

Detailed Description

The current standard for biopsy-based diagnoses of dysfunction of liver transplants is histology (the Banff system), an arbitrary international empirical consensus based on lesions and rules, similar in principle to the kidney, heart, and lung histology systems. Recent data-driven approaches using molecular and conventional technologies indicate that such systems frequently produce incorrect diagnoses - perhaps 40-50% in abnormal kidney or heart transplant biopsies and even more in lung biopsies, with great potential for harm to patients due to inappropriate treatment.

To address this unmet need and improve diagnostics in the area of organ transplantation, the Alberta Transplant Applied Genomics Centre (ATAGC, University of Alberta) has developed a new diagnostic system - the Molecular Microscope® Diagnostic System (MMDx) that interprets biopsies in terms of their molecular phenotype, and combines the molecular and histopathological features of transplant biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. The MMDx, developed first in kidney transplant biopsies because phenotypes are well established, will now be adapted to liver transplant biopsies. The present study will develop a Reference Set of liver biopsies, adapt the MMDx system to assess and report molecular phenotype of liver biopsies; and validate and refine this system in 300 unselected prospectively collected for clinical indications and a standard of care biopsies from North American and European Centers. In addition to demonstrating the real-time feasibility and potential value of this System in patient care, the study will develop and optimize a transparent and user-friendly reporting format to communicate this information to clinicians and obtain detailed feedback to improve its utility.

Thanks to increasing interest and support from participating centers, INTERLIVER has already received 861 biopsies from 739 participants and will extend the Reference Set to 900 biopsies.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-06-15
• Study First Submitted QC: 2017-06-15
• Study First Posted: 2017-06-20
• Study Start: 2017-12-19
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-02
• Last Update Posted: 2024-12-04
• Primary Completion: 2025-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• biopsy for clinical indications

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Exclusion Criteria

• no consent, pregnant women

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in liver transplant biopsies, in a reference set of 100 biopsies	two years	Based on the reference set, create molecular classifier that predicts antibody mediated and T cell mediated rejection for next 200 biopsies

Secondary Outcome Measures

Name	Time	Method
Assign in real time (two working days upon biopsy receipt) molecular scores (probability) of T cell mediated rejection and antibody mediated rejection.	1 year	The molecular phenotype of a newly acquired sample predicts the histologic and clinical features of this sample when compared to the reference set.

Trial Locations

Locations (15)

University of California San Francisco, Transplant Research Unit; 🇺🇸 San Francisco, California, United States

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States

University of Maryland School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Henry Ford Transplant Institute; 🇺🇸 Detroit, Michigan, United States

Vanderbilt University Medical Center, Vanderbilt Transplant Center; 🇺🇸 Nashville, Tennessee, United States

Baylor University Medical Center, Annette C. and Harold C. Simmons Transplant Institute; 🇺🇸 Dallas, Texas, United States

Transplant Surgery, VCU Medical Center; 🇺🇸 Richmond, Virginia, United States

Division of Transplant Surgery, University of Washington; 🇺🇸 Seattle, Washington, United States

Centenary Institute of Cancer Medicine & Cell Biology, Royal Prince Alfred Hospital; 🇦🇺 Camperdown, Australia

University of Alberta, Laboratory Medicine and Pathology; 🇨🇦 Edmonton, Alberta, Canada

Dep. of Nephrology, Transplantation & Internal Med., Samodzielny Publiczny Szpital Kliniczny im. A. Mieleckiego; 🇵🇱 Katowice, Poland

Independent Public Composite Regional Hospital; 🇵🇱 Szczecin, Poland

Warsaw Medical University, Jesus the Child Clinical Hospital; 🇵🇱 Warszawa, Poland

Warsaw Medical University, Independent Public Clinical Hospital; 🇵🇱 Warszawa, Poland

Institute for Liver Science, King's College London; 🇬🇧 London, United Kingdom