Molecular Diagnosis of Heart Allograft Rejection Using Intra-Graft Targeted Gene Expression Profiling.

NCT06436027 | Completed

• 1 other identifier: NANOHEART
• Study Type: observational
• Target: 496
• Locations: 3 countries
• Sites: 3

Brief Summary

The goal of this observational study is to develop and validate a molecular heart rejection diagnostic system based on targeted transcriptome as a novel monitoring companion tool for heart allograft precision diagnostics applicable to formalin-fixed paraffin-embedded endomyocardial biopsies. The primary outcome will be the biopsy-proven rejection, that will be predicted with molecular classifiers (cellular and antibody-mediated rejection scores).

Conditions

Heart Transplant Rejection

Keywords

molecular biology; allograft rejection; endomyocardial biopsy; pathology; precision diagnosis; heart transplantation

Outcome Measures

Primary Outcomes (1)

• Biopsy-proven rejection: acute cellular-rejection and antibody-mediated rejection.

  Prediction performances of the molecular classifiers (cellular and antibody-mediated rejection scores) to predict biopsy-proven rejection: diagnostic accuracy, Receiver Operating Characteristic - area under the curve, Precision Recall - area under the curve, Brier score, F1 score.

  1 month

Secondary Outcomes (1)

• Discrepancies between molecular and pathology diagnosis of rejection.

  1-month

Study Arms (2)

Development cohort

Random selection of 80% of the overall cohort.

Diagnostic Test: Nano-Heart tool: Intra-Graft Targeted Gene Expression Profiling

Validation cohort

Random selection of 20% of the overall cohort.

Diagnostic Test: Nano-Heart tool: Intra-Graft Targeted Gene Expression Profiling

Interventions

Nano-Heart tool: Intra-Graft Targeted Gene Expression Profiling DIAGNOSTIC_TEST

Targeted molecular profiling will be performed on formalin-fixed paraffin-embedded (FFPE) endomyocardial biopsies using the NanoString nCounter technology. A consortium-approved consensual targeted panel including 770 genes, developed by the Banff Molecular Diagnostics Working Group (MDWG) will be used.

Development cohort; Validation cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

We designed an international multicenter study, building a deep phenotyped cohort of heart transplant recipients recruited at 4 referral centers (Pitié-Salpêtrière and Georges Pompidou hospitals in Paris, Center Gallucci of the University General Hospital of Padova and the Cedars Sinai Medical Center in Los Angeles, USA).

You may qualify if:

• heart transplant recipients ≥ 18 years old
• at least one endomyocardial biopsy performed as part of routine clinical care
• biopsy performed at least ≥ 1 month post transplant and less that 10-year post-transplant
• written informed consent

You may not qualify if:

• age below 18 years old

Sponsors & Collaborators

• Paris Translational Research Center for Organ Transplantation: lead
• Cedars Sinai Medical Center, Los Angeles, USA: collaborator
• University of Padova: collaborator

Study Sites (3)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Paris Translational Research Center for Organ Transplantation

Paris, France

Location

Center Gallucci of the University General Hospital of Padova

Padua, Italy

Location

Related Publications (7)

• Berry GJ, Burke MM, Andersen C, Bruneval P, Fedrigo M, Fishbein MC, Goddard M, Hammond EH, Leone O, Marboe C, Miller D, Neil D, Rassl D, Revelo MP, Rice A, Rene Rodriguez E, Stewart S, Tan CD, Winters GL, West L, Mehra MR, Angelini A. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2013 Dec;32(12):1147-62. doi: 10.1016/j.healun.2013.08.011.

  PMID: 24263017 BACKGROUND

• Halloran PF, Venner JM, Madill-Thomsen KS, Einecke G, Parkes MD, Hidalgo LG, Famulski KS. Review: The transcripts associated with organ allograft rejection. Am J Transplant. 2018 Apr;18(4):785-795. doi: 10.1111/ajt.14600. Epub 2017 Dec 23.

  PMID: 29178397 BACKGROUND

• 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.

  PMID: 28662985 BACKGROUND

• Mengel M, Loupy A, Haas M, Roufosse C, Naesens M, Akalin E, Clahsen-van Groningen MC, Dagobert J, Demetris AJ, Duong van Huyen JP, Gueguen J, Issa F, Robin B, Rosales I, Von der Thusen JH, Sanchez-Fueyo A, Smith RN, Wood K, Adam B, Colvin RB. Banff 2019 Meeting Report: Molecular diagnostics in solid organ transplantation-Consensus for the Banff Human Organ Transplant (B-HOT) gene panel and open source multicenter validation. Am J Transplant. 2020 Sep;20(9):2305-2317. doi: 10.1111/ajt.16059. Epub 2020 Jun 27.

  PMID: 32428337 BACKGROUND

• Giarraputo A, Coutance G, Aubert O, Fedrigo M, Mezine F, Zielinski D, Mengel M, Bruneval P, Duong van Huyen JP, Angelini A, Loupy A. Banff Human Organ Transplant Consensus Gene Panel for the Detection of Antibody Mediated Rejection in Heart Allograft Biopsies. Transpl Int. 2023 Sep 4;36:11710. doi: 10.3389/ti.2023.11710. eCollection 2023.

  PMID: 37745639 BACKGROUND

• Coutance G, Zouhry I, Racape M, Drieux F, Viailly PJ, Rouvier P, Francois A, Chenard MP, Toquet C, Rabant M, Berry GJ, Angelini A, Bruneval P, Duong Van Huyen JP. Correlation Between Microvascular Inflammation in Endomyocardial Biopsies and Rejection Transcripts, Donor-specific Antibodies, and Graft Dysfunction in Antibody-mediated Rejection. Transplantation. 2022 Jul 1;106(7):1455-1464. doi: 10.1097/TP.0000000000004008. Epub 2021 Dec 21.

  PMID: 34954735 BACKGROUND

• Duong Van Huyen JP, Fedrigo M, Fishbein GA, Leone O, Neil D, Marboe C, Peyster E, von der Thusen J, Loupy A, Mengel M, Revelo MP, Adam B, Bruneval P, Angelini A, Miller DV, Berry GJ. The XVth Banff Conference on Allograft Pathology the Banff Workshop Heart Report: Improving the diagnostic yield from endomyocardial biopsies and Quilty effect revisited. Am J Transplant. 2020 Dec;20(12):3308-3318. doi: 10.1111/ajt.16083. Epub 2020 Jun 28.

  PMID: 32476272 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Use of formalin-fixed paraffin-embedded endomyocardial biopsies collected prospectively as part of the standard clinical care of heart transplant recipients.

Study Officials

• Alexandre Loupy, MD, PhD

  Paris Translational Research Center for Organ Transplantation

  STUDY DIRECTOR

• Guillaume Coutance, MD, PhD

  Paris Translational Research Center for Organ Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2024
• First Posted: May 30, 2024
• Study Start: November 10, 2021
• Primary Completion: December 15, 2023
• Study Completion: December 15, 2023
• Last Updated: May 30, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); FR (1); IT (1)