Diagnostic and Therapeutic Applications of Microarrays in Liver Transplantation

NCT ID: NCT03193151

Last Updated: 2025-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

300 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-12-19

Study Completion Date

2027-12-31

Brief Summary

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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

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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 856 biopsies from 740 participants and will extend the Reference Set to 900 biopsies.

Conditions

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Liver Dysfunction

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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liver biopsy

5 mm fragment of liver transplant biopsy taken for clinical indication

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* biopsy for clinical indications

Exclusion Criteria

* no consent, pregnant women
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Alberta

OTHER

Sponsor Role lead

Responsible Party

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Philip Halloran

Distinguished Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Philip F Halloran, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

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University of California San Francisco, Transplant Research Unit

San Francisco, California, United States

Site Status COMPLETED

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status COMPLETED

University of Maryland School of Medicine

Baltimore, Maryland, United States

Site Status COMPLETED

Henry Ford Transplant Institute

Detroit, Michigan, United States

Site Status RECRUITING

Vanderbilt University Medical Center, Vanderbilt Transplant Center

Nashville, Tennessee, United States

Site Status WITHDRAWN

Baylor University Medical Center, Annette C. and Harold C. Simmons Transplant Institute

Dallas, Texas, United States

Site Status COMPLETED

Transplant Surgery, VCU Medical Center

Richmond, Virginia, United States

Site Status COMPLETED

Division of Transplant Surgery, University of Washington

Seattle, Washington, United States

Site Status COMPLETED

Centenary Institute of Cancer Medicine & Cell Biology, Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status COMPLETED

University of Alberta, Laboratory Medicine and Pathology

Edmonton, Alberta, Canada

Site Status COMPLETED

Dep. of Nephrology, Transplantation & Internal Med., Samodzielny Publiczny Szpital Kliniczny im. A. Mieleckiego

Katowice, , Poland

Site Status COMPLETED

Independent Public Composite Regional Hospital

Szczecin, , Poland

Site Status COMPLETED

Warsaw Medical University, Jesus the Child Clinical Hospital

Warsaw, , Poland

Site Status COMPLETED

Warsaw Medical University, Independent Public Clinical Hospital

Warsaw, , Poland

Site Status COMPLETED

Institute for Liver Science, King's College London

London, , United Kingdom

Site Status COMPLETED

Countries

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United States Australia Canada Poland United Kingdom

Central Contacts

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Konrad S Famulski, PhD

Role: CONTACT

1 780 492 1725

Robert Polakowski, PhD

Role: CONTACT

1 780 492 5091

Facility Contacts

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Dilip Moonka, MD

Role: primary

Sierra Foley

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 38819301 (View on PubMed)

Madill-Thomsen KS, Gauthier PT, Abouljoud M, Bhati C, Bruno D, Ciszek M, Durlik M, Feng S, Foroncewicz B, Grat M, Jurczyk K, Levitsky J, McCaughan G, Maluf D, Montano-Loza A, Moonka D, Mucha K, Myslak M, Perkowska-Ptasinska A, Piecha G, Reichman T, Tronina O, Wawrzynowicz-Syczewska M, Zeair S, Halloran PF. Defining an NK Cell-enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study. Transplantation. 2025 Aug 1;109(8):1367-1382. doi: 10.1097/TP.0000000000005269. Epub 2025 Jan 9.

Reference Type RESULT
PMID: 39780312 (View on PubMed)

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, Reichman T, Sanchez-Fueyo A, Tronina O, Wawrzynowicz-Syczewska M, Wiecek A, Zieniewicz K, Halloran PF. The molecular diagnosis of rejection in liver transplant biopsies: First results of the INTERLIVER study. Am J Transplant. 2020 Aug;20(8):2156-2172. doi: 10.1111/ajt.15828. Epub 2020 Apr 9.

Reference Type RESULT
PMID: 32090446 (View on PubMed)

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.

Reference Type RESULT
PMID: 34780106 (View on PubMed)

Halloran PF. Integrating molecular and histologic interpretation of transplant biopsies. Clin Transplant. 2021 Apr;35(4):e14244. doi: 10.1111/ctr.14244. Epub 2021 Feb 17. No abstract available.

Reference Type DERIVED
PMID: 33595110 (View on PubMed)

Other Identifiers

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ATAGC04

Identifier Type: -

Identifier Source: org_study_id

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