Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation

Liver Dysfunction Clinical Trial

— INTERLIVER  

Official title:

Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation, a Multicenter Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03193151
• Other study ID #: ATAGC04
• Status: Recruiting
• Start date: December 19, 2017
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: University of Alberta
• Contact: Konrad S Famulski, PhD
• Phone: 1 780 492 1725
• Email: konrad[@]ualberta.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 processed 849 biopsies from 732 participants and will extend the Reference Set to 950 biopsies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• 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:

• biopsy for clinical indications

Exclusion Criteria:

• no consent, pregnant women

Related Conditions & MeSH terms

• Liver Diseases
• Liver Dysfunction

Intervention

Procedure:
• liver biopsy
5 mm fragment of liver transplant biopsy taken for clinical indication

Locations

Country	Name	City	State
Australia	Centenary Institute of Cancer Medicine & Cell Biology, Royal Prince Alfred Hospital	Camperdown
Canada	University of Alberta, Laboratory Medicine and Pathology	Edmonton	Alberta
Poland	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, Independent Public Clinical Hospital	Warszawa
Poland	Warsaw Medical University, Jesus the Child Clinical Hospital	Warszawa
United Kingdom	Institute for Liver Science, King's College London	London
United States	University of Maryland School of Medicine	Baltimore	Maryland
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Baylor University Medical Center, Annette C. and Harold C. Simmons Transplant Institute	Dallas	Texas
United States	Henry Ford Transplant Institute	Detroit	Michigan
United States	Vanderbilt University Medical Center, Vanderbilt Transplant Center	Nashville	Tennessee
United States	Transplant Surgery, VCU Medical Center	Richmond	Virginia
United States	University of California San Francisco, Transplant Research Unit	San Francisco	California
United States	Division of Transplant Surgery, University of Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Poland,  United Kingdom, 

References & Publications (3)

Madill-Thomsen K, Abouljoud M, Bhati C, Ciszek M, Durlik M, Feng S, Foroncewicz B, Francis I, Grat M, Jurczyk K, Klintmalm G, Krasnodebski M, McCaughan G, Miquel R, Montano-Loza A, Moonka D, Mucha K, Myslak M, Paczek L, Perkowska-Ptasinska A, Piecha G, Re — View Citation

Madill-Thomsen KS, Abouljoud M, Bhati C, Ciszek M, Durlik M, Feng S, Foroncewicz B, Francis I, Grat M, Jurczyk K, Klintmalm G, Krasnodebski M, McCaughan G, Miquel R, Montano-Loza A, Moonka D, Mucha K, Myslak M, Paczek L, Perkowska-Ptasinska A, Piecha G, Reichman T, Sanchez-Fueyo A, Tronina O, Wawrzynowicz-Syczewska M, Wiecek A, Zieniewicz K, Halloran PF. The molecular phenotypes of injury, steatohepatitis, and fibrosis in liver transplant biopsies in the INTERLIVER study. Am J Transplant. 2022 Mar;22(3):909-926. doi: 10.1111/ajt.16890. Epub 2021 Dec 3. — View Citation

Madill-Thomsen KS, Halloran PF. Precision diagnostics in transplanted organs using microarray-assessed gene expression: concepts and technical methods of the Molecular Microscope(R) Diagnostic System (MMDx). Clin Sci (Lond). 2024 Jun 5;138(11):663-685. doi: 10.1042/CS20220530. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in liver transplant biopsies, in a reference set of 100 biopsies	Based on the reference set, create molecular classifier that predicts antibody mediated and T cell mediated rejection for next 200 biopsies	two years
Secondary	Assign in real time (two working days upon biopsy receipt) molecular scores (probability) of T cell mediated rejection and antibody mediated rejection.	The molecular phenotype of a newly acquired sample predicts the histologic and clinical features of this sample when compared to the reference set.	1 year