Diagnostic and Therapeutic Applications of Microarrays in Heart Transplantation

NCT ID: NCT02670408

Last Updated: 2025-12-01

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

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

900 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-01-31

Study Completion Date

2027-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Demonstrate the impact of the Molecular Microscope Diagnostic System as the standard of care for heart transplant patients.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The current standard for biopsy-based diagnoses of rejection of heart transplants is the ISHLT classification from 2004, which represents a widely-used international consensus, based on morphological criteria of the cellular infiltrate within the myocardial specimen system with certainties and some arbitrary and blurred parameters. Recent data-driven approaches using molecular and conventional technologies indicate that this system produces incorrect diagnoses with potential 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 heart transplant endomyocardial biopsies (EMBs). The present study will develop a Reference Set of EMB, adapt the MMDx system to assess and report EMBs; and validate and refine this system in 900 unselected prospectively collected for clinical indications and a standard of care EMBs 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. We refine now our MMDx system using a new type of analysis (see primary outcome) and the resulting MMDx report. Currently, INTERHEART recruited 1912 biopsies from 1279 patients.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cardiac Transplant Disorder

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Endomyocardial biopsy

One of several endomyocardial biopsy bites taken as the standard of care. We are asking now for two endomyocardial biopsy bites, to determine tissue sampling variability.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Alberta

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Philip Halloran

Distinguished Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Philip F Halloran, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UCLA Medical Centre

Los Angeles, California, United States

Site Status COMPLETED

Cedars-Sinai Heart Institute

Los Angeles, California, United States

Site Status COMPLETED

Annette C. and Harold C. Simmons Transplant Institute, BaylorScott&White Research Institute

Dallas, Texas, United States

Site Status COMPLETED

Cardiovascular Medicine, University of Utah Health

Salt Lake City, Utah, United States

Site Status COMPLETED

Virginia Commonwealth University, Division of Cardiology

Richmond, Virginia, United States

Site Status COMPLETED

Cardiac Transplantation Laboratory, The Victor Chang Cardiac Research Institute

Darlinghurst, , Australia

Site Status RECRUITING

Department of Cardiac Surgery, Medical University of Vienna

Vienna, , Austria

Site Status RECRUITING

Alberta Transplant Applied Genomics Center, University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

Division of Cardiology, University of Alberta

Edmonton, Alberta, Canada

Site Status COMPLETED

Institute for Clinical and Experimental Medicine - IKEM

Prague, , Czechia

Site Status RECRUITING

Service de Néphrologie-Dialyse Adultes , Hôpital Necker-Enfants Malades

Paris, , France

Site Status COMPLETED

Heart Failure and Heart Transplant Unit, University of Bologna

Bologna, , Italy

Site Status COMPLETED

Advanced Heart Failure Transplant Unit

A Coruña, , Spain

Site Status COMPLETED

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Austria Canada Czechia France Italy Spain

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Konrad S Famulski, PhD

Role: CONTACT

1 7804921725

Robert Polakowski, PhD

Role: CONTACT

1780 492 5091

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Carmen Herrera, MD

Role: primary

61-02-8382-3025

Arezu Aliabadi, MD

Role: primary

43-1-40400-5643

MD

Role: backup

Konrad Famulski, PhD

Role: primary

7804921725

Tereza Novakowa

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

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)

Loupy A, Duong Van Huyen JP, Hidalgo L, Reeve J, Racape M, Aubert O, Venner JM, Falmuski K, Bories MC, Beuscart T, Guillemain R, Francois A, Pattier S, Toquet C, Gay A, Rouvier P, Varnous S, Leprince P, Empana JP, Lefaucheur C, Bruneval P, Jouven X, Halloran PF. Gene Expression Profiling for the Identification and Classification of Antibody-Mediated Heart Rejection. Circulation. 2017 Mar 7;135(10):917-935. doi: 10.1161/CIRCULATIONAHA.116.022907. Epub 2017 Feb 1.

Reference Type RESULT
PMID: 28148598 (View on PubMed)

Halloran PF, Potena L, Van Huyen JD, Bruneval P, Leone O, Kim DH, Jouven X, Reeve J, Loupy A. Building a tissue-based molecular diagnostic system in heart transplant rejection: The heart Molecular Microscope Diagnostic (MMDx) System. J Heart Lung Transplant. 2017 Nov;36(11):1192-1200. doi: 10.1016/j.healun.2017.05.029. Epub 2017 May 29.

Reference Type RESULT
PMID: 28662985 (View on PubMed)

Halloran PF, Reeve J, Aliabadi AZ, Cadeiras M, Crespo-Leiro MG, Deng M, Depasquale EC, Goekler J, Jouven X, Kim DH, Kobashigawa J, Loupy A, Macdonald P, Potena L, Zuckermann A, Parkes MD. Exploring the cardiac response to injury in heart transplant biopsies. JCI Insight. 2018 Oct 18;3(20):e123674. doi: 10.1172/jci.insight.123674.

Reference Type RESULT
PMID: 30333303 (View on PubMed)

Parkes MD, Aliabadi AZ, Cadeiras M, Crespo-Leiro MG, Deng M, Depasquale EC, Goekler J, Kim DH, Kobashigawa J, Loupy A, Macdonald P, Potena L, Zuckermann A, Halloran PF. An integrated molecular diagnostic report for heart transplant biopsies using an ensemble of diagnostic algorithms. J Heart Lung Transplant. 2019 Jun;38(6):636-646. doi: 10.1016/j.healun.2019.01.1318. Epub 2019 Feb 6.

Reference Type RESULT
PMID: 30795962 (View on PubMed)

Halloran PF, Madill-Thomsen KS. The Molecular Microscope Diagnostic System: Assessment of Rejection and Injury in Heart Transplant Biopsies. Transplantation. 2023 Jan 1;107(1):27-44. doi: 10.1097/TP.0000000000004323. Epub 2022 Dec 8.

Reference Type RESULT
PMID: 36508644 (View on PubMed)

Halloran PF, Madill-Thomsen K, Mackova M, Aliabadi-Zuckermann AZ, Cadeiras M, Crespo-Leiro MG, Depasquale EC, Deng M, Gokler J, Hall SA, Kim DH, Kobashigawa J, Macdonald P, Potena L, Shah K, Stehlik J, Zuckermann A, Reeve J. Molecular states associated with dysfunction and graft loss in heart transplants. J Heart Lung Transplant. 2024 Mar;43(3):508-518. doi: 10.1016/j.healun.2023.11.013. Epub 2023 Nov 30.

Reference Type RESULT
PMID: 38042442 (View on PubMed)

Halloran PF, Madill-Thomsen K, Aliabadi-Zuckermann AZ, Cadeiras M, Crespo-Leiro MG, Depasquale EC, Deng M, Gokler J, Kim DH, Kobashigawa J, Macdonald P, Potena L, Shah K, Stehlik J, Zuckermann A. Many heart transplant biopsies currently diagnosed as no rejection have mild molecular antibody-mediated rejection-related changes. J Heart Lung Transplant. 2022 Mar;41(3):334-344. doi: 10.1016/j.healun.2021.08.004. Epub 2021 Aug 26.

Reference Type RESULT
PMID: 34548198 (View on PubMed)

Halloran PF, Madill-Thomsen K, Aliabadi-Zuckermann AZ, Cadeiras M, Crespo-Leiro MG, Depasquale EC, Deng M, Gokler J, Hall S, Jamil A, Kim DH, Kobashigawa J, Macdonald P, Melenovsky V, Patel J, Potena L, Shah K, Stehlik J, Zuckermann A. Redefining the molecular rejection states in 3230 heart transplant biopsies: Relationships to parenchymal injury and graft survival. Am J Transplant. 2024 Aug;24(8):1414-1426. doi: 10.1016/j.ajt.2024.03.031. Epub 2024 Mar 26.

Reference Type RESULT
PMID: 38527588 (View on PubMed)

Madill-Thomsen KS, Reeve J, Aliabadi-Zuckermann A, Cadeiras M, Crespo-Leiro MG, Depasquale EC, Deng M, Goekler J, Kim DH, Kobashigawa J, Macdonald P, Potena L, Shah K, Stehlik J, Zuckermann A, Halloran PF. Assessing the Relationship Between Molecular Rejection and Parenchymal Injury in Heart Transplant Biopsies. Transplantation. 2022 Nov 1;106(11):2205-2216. doi: 10.1097/TP.0000000000004231. Epub 2022 Oct 21.

Reference Type DERIVED
PMID: 35968995 (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

Review additional registry numbers or institutional identifiers associated with this trial.

ATAGC 002

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Trifecta-Heart cfDNA-MMDx Study
NCT04707872 RECRUITING
The SMARTER Cardiomyopathy Study
NCT05750147 RECRUITING