Diagnostic and Therapeutic Applications of Microarrays in Heart Transplantation

Cardiac Transplant Disorder Clinical Trial

Official title:

Diagnostic and Therapeutic Applications of Microarrays in Heart Transplantation, a Multicenter Study (INTERHEART)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02670408
• Other study ID #: ATAGC 002
• Status: Recruiting
• Start date: January 2016
• Est. completion date: July 2025

Study information

• Verified date: June 2024
• Source: University of Alberta
• Contact: Konrad S Famulski, PhD
• Phone: 1 7804921725
• Email: konrad[@]ualberta.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

Description:

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 1859 biopsies from 1233 patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 900
• Est. completion date: July 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

• Cardiac Transplant Disorder

Intervention

Procedure:
• 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.

Locations

Country	Name	City	State
Australia	Cardiac Transplantation Laboratory, The Victor Chang Cardiac Research Institute	Darlinghurst
Austria	Department of Cardiac Surgery, Medical University of Vienna	Vienna
Canada	Alberta Transplant Applied Genomics Center, University of Alberta	Edmonton	Alberta
Canada	Division of Cardiology, University of Alberta	Edmonton	Alberta
France	Service de Néphrologie-Dialyse Adultes , Hôpital Necker-Enfants Malades	Paris
Italy	Heart Failure and Heart Transplant Unit, University of Bologna	Bologna
Spain	Advanced Heart Failure Transplant Unit	La Coruna
United States	Cedars-Sinai Heart Institute	Los Angeles	California
United States	UCLA Medical Centre	Los Angeles	California
United States	Virginia Commonwealth University, Division of Cardiology	Richmond	Virginia
United States	Cardiovascular Medicine, University of Utah Health	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Alberta

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  France,  Italy,  Spain, 

References & Publications (9)

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 mole — View Citation

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 re — View Citation

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 wi — View Citation

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. — View Citation

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 Transpla — View Citation

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 biopsi — View Citation

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, Hallo — 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

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 ensem — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assign molecular scores (probability) of T cell mediated rejection, antibody mediated rejection in heart transplant biopsies, in a reference set of 200 biopsies	Create a molecular classifier that predicts antibody mediated and T cell mediated rejection, based on the archetypal analysis.	2 years
Secondary	Assign in real time (three 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