Development of Reporting System for Molecular Diagnosis Clinical Trial
Official title:
Multi-centric Observational Study to Analyse the Diagnostic Molecular Features in the Clinical Setting of Kidney Allograft Biopsies
| NCT number | NCT01299168 |
| Other study ID # | ATAGC-001 |
| Secondary ID | |
| Status | Recruiting |
| Phase | |
| First received | |
| Last updated | |
| Start date | May 2011 |
| Est. completion date | June 2025 |
The current standard for biopsy-based diagnoses of dysfunction of kidney transplants is the Banff Classification which represents arbitrary international consensus. Recent data-driven approaches using molecular and conventional technologies indicate that mere consensus produces frequently 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) has developed a new diagnostic system that combines the molecular and histopathological features of transplant biopsies, plus clinical and laboratory parameters, to create the first Integrated Diagnostic System. The present study will validate and refine this system in 500 prospectively unselected biopsies for clinical indications from American, Canadian and European centres in addition to 300 biopsies already collected. Due to a considerable interest and support from participating Centers, the study is further extended to 1500 prospective biopsies. Thus this is the extension of the INTERCOM study (INTERCOMEX). In addition to demonstrating the feasibility and value of this System in routine patient care and clinical trials, the study will develop and optimize a transparent and user-friendly reporting format to communicate this information to clinicians and obtain detailed feedback on how this system can best improve patient care.
| Status | Recruiting |
| Enrollment | 500 |
| Est. completion date | June 2025 |
| Est. primary completion date | December 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - All kidney transplant recipients =18yrs of age undergoing a kidney biopsy for clinical indications, as determined by their physician or surgeon, will be eligible to enrol in the study. Exclusion Criteria: - Patients will be excluded from the study if they decline participation or are unable to give informed consent. |
| Country | Name | City | State |
|---|---|---|---|
| Austria | Medical University of Vienna | Vienna | |
| Canada | Department of Medicine, University of Alberta | Edmonton | Alberta |
| Canada | University of British Columbia, St. Paul's Hospital | Vancouver | British Columbia |
| Croatia | University Hospital Merkur | Zagreb | |
| Czechia | Institute for Experimental and Clinical Medicine (IKEM) | Prague | |
| France | Hopital Necker | Paris | |
| France | Hopital St. Louis | Paris | |
| Germany | Charité - Universitätmedizin Berlin | Berlin | |
| Germany | Medizinische Hochschule | Hannover | |
| Ireland | Beaumont Hospital | Dublin | |
| Korea, Republic of | Department of Surgery, University of Usan, College of Medicine | Seoul | |
| Poland | Pomeranian Medical University in Szczecin | Szczecin | |
| Slovenia | University of Ljubljana | Ljubljana | |
| Spain | Vall d'Hebron Hospital | Barcelona | |
| Switzerland | University Hospital Zurich | Zürich | |
| United Kingdom | Manchester Royal Infirmary | Manchester | |
| United States | University of Michigan Health System | Ann Arbor | Michigan |
| United States | University of Maryland School of Medicine | Baltimore | Maryland |
| United States | University of Alabama | Birmingham | Alabama |
| United States | Montefiore Medical Center | Bronx | New York |
| United States | Pinnacle Transplant Associates | Harrisburg | Pennsylvania |
| United States | University of Wisconsin School of Medicine and Public Health | Madison | Wisconsin |
| United States | University of Minnesota | Minneapolis | Minnesota |
| United States | Virginia Commonwealth University School of Medicine | Richmond | Virginia |
| United States | Barnes-Jewish Hospital | Saint Louis | Missouri |
| United States | Texas Transplant Institute - Methodist Healthcare System | San Antonio | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| University of Alberta |
United States, Austria, Canada, Croatia, Czechia, France, Germany, Ireland, Korea, Republic of, Poland, Slovenia, Spain, Switzerland, United Kingdom,
Aubert O, Loupy A, Hidalgo L, Duong van Huyen JP, Higgins S, Viglietti D, Jouven X, Glotz D, Legendre C, Lefaucheur C, Halloran PF. Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients. J A — View Citation
Einecke G, Reeve J, Gupta G, Bohmig GA, Eskandary F, Bromberg JS, Budde K, Halloran PF; INTERCOMEX investigators. Factors associated with kidney graft survival in pure antibody-mediated rejection at the time of indication biopsy: Importance of parenchymal injury but not disease activity. Am J Transplant. 2021 Apr;21(4):1391-1401. doi: 10.1111/ajt.16161. Epub 2020 Jul 31. — View Citation
Eskandary F, Bond G, Kozakowski N, Regele H, Marinova L, Wahrmann M, Kikic Z, Haslacher H, Rasoul-Rockenschaub S, Kaltenecker CC, Konig F, Hidalgo LG, Oberbauer R, Halloran PF, Bohmig GA. Diagnostic Contribution of Donor-Specific Antibody Characteristics — View Citation
Halloran PF, Bohmig GA, Bromberg J, Einecke G, Eskandary FA, Gupta G, Myslak M, Viklicky O, Perkowska-Ptasinska A, Madill-Thomsen KS; INTERCOMEX Investigators. Archetypal Analysis of Injury in Kidney Transplant Biopsies Identifies Two Classes of Early AKI — View Citation
Halloran PF, Chang J, Famulski K, Hidalgo LG, Salazar ID, Merino Lopez M, Matas A, Picton M, de Freitas D, Bromberg J, Seron D, Sellares J, Einecke G, Reeve J. Disappearance of T Cell-Mediated Rejection Despite Continued Antibody-Mediated Rejection in Lat — View Citation
Halloran PF, Famulski KS, Reeve J. Molecular assessment of disease states in kidney transplant biopsy samples. Nat Rev Nephrol. 2016 Sep;12(9):534-48. doi: 10.1038/nrneph.2016.85. Epub 2016 Jun 27. — View Citation
Halloran PF, Madill-Thomsen KS, Reeve J. The Molecular Phenotype of Kidney Transplants: Insights From the MMDx Project. Transplantation. 2024 Jan 1;108(1):45-71. doi: 10.1097/TP.0000000000004624. Epub 2023 Dec 13. — View Citation
Halloran PF, Matas A, Kasiske BL, Madill-Thomsen KS, Mackova M, Famulski KS. Molecular phenotype of kidney transplant indication biopsies with inflammation in scarred areas. Am J Transplant. 2019 May;19(5):1356-1370. doi: 10.1111/ajt.15178. Epub 2018 Dec — View Citation
Halloran PF, Merino Lopez M, Barreto Pereira A. Identifying Subphenotypes of Antibody-Mediated Rejection in Kidney Transplants. Am J Transplant. 2016 Mar;16(3):908-20. doi: 10.1111/ajt.13551. Epub 2016 Jan 6. — View Citation
Halloran PF, Pereira AB, Chang J, Matas A, Picton M, De Freitas D, Bromberg J, Seron D, Sellares J, Einecke G, Reeve J. Microarray diagnosis of antibody-mediated rejection in kidney transplant biopsies: an international prospective study (INTERCOM). Am J — View Citation
Halloran PF, Pereira AB, Chang J, Matas A, Picton M, De Freitas D, Bromberg J, Seron D, Sellares J, Einecke G, Reeve J. Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: The INTERCOM study. Am J Transplant. 2013 — View Citation
Halloran PF, Reeve J, Akalin E, Aubert O, Bohmig GA, Brennan D, Bromberg J, Einecke G, Eskandary F, Gosset C, Duong Van Huyen JP, Gupta G, Lefaucheur C, Malone A, Mannon RB, Seron D, Sellares J, Weir M, Loupy A. Real Time Central Assessment of Kidney Tran — View Citation
Halloran PF, Venner JM, Famulski KS. Comprehensive Analysis of Transcript Changes Associated With Allograft Rejection: Combining Universal and Selective Features. Am J Transplant. 2017 Jul;17(7):1754-1769. doi: 10.1111/ajt.14200. Epub 2017 Feb 25. — View Citation
Loupy A, Lefaucheur C, Vernerey D, Chang J, Hidalgo LG, Beuscart T, Verine J, Aubert O, Dubleumortier S, Duong van Huyen JP, Jouven X, Glotz D, Legendre C, Halloran PF. Molecular microscope strategy to improve risk stratification in early antibody-mediate — View Citation
Madill-Thomsen K, Perkowska-Ptasinska A, Bohmig GA, Eskandary F, Einecke G, Gupta G, Halloran PF; MMDx-Kidney Study Group. Discrepancy analysis comparing molecular and histology diagnoses in kidney transplant biopsies. Am J Transplant. 2020 May;20(5):1341 — View Citation
Madill-Thomsen KS, Bohmig GA, Bromberg J, Einecke G, Eskandary F, Gupta G, Myslak M, Viklicky O, Perkowska-Ptasinska A, Solez K, Halloran PF; the INTERCOMEX Investigators. Relating Molecular T Cell-mediated Rejection Activity in Kidney Transplant Biopsies — 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
Madill-Thomsen KS, Wiggins RC, Eskandary F, Bohmig GA, Halloran PF. The Effect of Cortex/Medulla Proportions on Molecular Diagnoses in Kidney Transplant Biopsies: Rejection and Injury Can Be Assessed in Medulla. Am J Transplant. 2017 Aug;17(8):2117-2128. — View Citation
Reeve J, Bohmig GA, Eskandary F, Einecke G, Gupta G, Madill-Thomsen K, Mackova M, Halloran PF; INTERCOMEX MMDx-Kidney Study Group. Generating automated kidney transplant biopsy reports combining molecular measurements with ensembles of machine learning cl — View Citation
Reeve J, Bohmig GA, Eskandary F, Einecke G, Lefaucheur C, Loupy A, Halloran PF; MMDx-Kidney study group. Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes. JCI Insight. 2017 Jun 15;2(12) — View Citation
Reeve J, Chang J, Salazar ID, Lopez MM, Halloran PF. Using Molecular Phenotyping to Guide Improvements in the Histologic Diagnosis of T Cell-Mediated Rejection. Am J Transplant. 2016 Apr;16(4):1183-92. doi: 10.1111/ajt.13572. Epub 2016 Jan 5. — View Citation
Sikosana MLN, Reeve J, Madill-Thomsen KS, Halloran PF; INTERCOMEX Investigators. Using Regression Equations to Enhance Interpretation of Histology Lesions of Kidney Transplant Rejection. Transplantation. 2024 Feb 1;108(2):445-454. doi: 10.1097/TP.00000000 — View Citation
* Note: There are 22 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Validate the Integrated Diagnostic System in the International Collaborative Microarray (INTERCOM) Study | The rejection classifier predicts Banff diagnosis of any rejection: ABMR, TCMR, or mixed ABMR and TCMR;
The TCMR classifier predicts the presence of Banff TCMR lesions/diagnoses; The ABMR classifier predicts the presence of ABMR lesions; In late (>1yr) biopsies for clinical indications, the failure classifier predicts failure within three years. |
2013-2016 | |
| Secondary | Demonstrate the feasibility of molecular phenotyping of 300 + 500 kidney transplant biopsies for clinical indications. | To test the hypothesis that the molecular phenotype of a newly acquired sample predicts the histologic and clinical features of this sample. | 2014-2016 | |
| Secondary | Demonstrate the feasibility of molecular phenotyping of 500 biopsies in real time i.e. returning the molecular phenotyping report in two working days upon sample arrival. | Refine the reports based on feedback from the participants. | 2015-2016 |