Ignite Creation Date:
2024-06-16 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06436027
Status:
COMPLETED
Last Update Posted:
2024-05-30
First Post:
2024-05-14
Brief Title:
Molecular Diagnosis of Heart Allograft Rejection Using Intra-Graft Targeted Gene Expression Profiling
Sponsor:
Paris Translational Research Center for Organ Transplantation
Organization:
Paris Translational Research Center for Organ Transplantation
Study Overview
Official Title:
Molecular Diagnosis of Heart Allograft Rejection Using Intra-Graft Targeted Gene Expression Profiling
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Nano-Heart
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
The primary outcome will be the biopsy-proven rejection that will be predicted with molecular classifiers cellular and antibody-mediated rejection scores
Detailed Description:
Heart transplantation HTx remains the most valuable therapeutic option for patients with end-stage heart failure refractory to optimal medical therapy Despite major improvements in immunosuppression and transplant care acute and chronic rejection-induced allograft injuries remain one of the leading causes of mortality and morbidity after heart transplantation thus limiting recipients life expectancy An improvement in the overall management of rejection remains an unmet medical need As a first step a precise diagnosis of rejection is crucial to guide patient care and optimize management
Nowadays the diagnosis of cardiac rejection relies exclusively on the pathological assessment of endomyocardial biopsies EMBs by identifying and grading cellular infiltrates and myocardial damage While important advances have been made in the standardization of the rejection diagnosis pathology remains an imperfect gold-standard particularly due to the inter-observer variability sample bias and the use of qualitative or semi-quantitative scales that oversimplify complex phenotypes Additionally disease severity degree of myocardial injury and progression stage are crucial pieces of information poorly captured by the current working formulations All these limits represent major barriers to achieve a precise and reliable diagnosis of rejection
In this context gene expression profiling analysis of fresh myocardial samples retrieved during an extra-core biopsy and using a whole transcriptome approach arose as a potential objective companion tool of pathology to refine the diagnosis of rejection However important drawbacks have limited the routine clinical applicability of whole-transcriptome based molecular diagnosis including extra-core sampling bias low reproducibility technical and analytical heaviness with costs and sample turn-around that is not compatible with a clinical setting
Recent technologies may overcome this limitation by allowing analysis of the same tissue used for histology assessment Targeted molecular profiling applicable to formalin-fixed paraffin-embedded FFPE endomyocardial biopsies may allow the implementation of molecular diagnosis into the clinical routine Recently we have shown that the Banff Human Organ Transplant Panel B-HOT panel a consortium-approved consensual targeted panel including 770 genes developed by the Banff Molecular Diagnostics Working Group accurately captured key molecular patterns of antibody-mediated rejection AMR in heart allograft biopsies and may serve as a proxy to whole transcriptome-based analysis
The aim of the present study is therefore to identify gene expression signatures for AMR and acute cellular rejection in heart transplantation and 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 FFPE-EMB
Nowadays the diagnosis of cardiac rejection relies exclusively on the pathological assessment of endomyocardial biopsies EMBs by identifying and grading cellular infiltrates and myocardial damage While important advances have been made in the standardization of the rejection diagnosis pathology remains an imperfect gold-standard particularly due to the inter-observer variability sample bias and the use of qualitative or semi-quantitative scales that oversimplify complex phenotypes Additionally disease severity degree of myocardial injury and progression stage are crucial pieces of information poorly captured by the current working formulations All these limits represent major barriers to achieve a precise and reliable diagnosis of rejection
In this context gene expression profiling analysis of fresh myocardial samples retrieved during an extra-core biopsy and using a whole transcriptome approach arose as a potential objective companion tool of pathology to refine the diagnosis of rejection However important drawbacks have limited the routine clinical applicability of whole-transcriptome based molecular diagnosis including extra-core sampling bias low reproducibility technical and analytical heaviness with costs and sample turn-around that is not compatible with a clinical setting
Recent technologies may overcome this limitation by allowing analysis of the same tissue used for histology assessment Targeted molecular profiling applicable to formalin-fixed paraffin-embedded FFPE endomyocardial biopsies may allow the implementation of molecular diagnosis into the clinical routine Recently we have shown that the Banff Human Organ Transplant Panel B-HOT panel a consortium-approved consensual targeted panel including 770 genes developed by the Banff Molecular Diagnostics Working Group accurately captured key molecular patterns of antibody-mediated rejection AMR in heart allograft biopsies and may serve as a proxy to whole transcriptome-based analysis
The aim of the present study is therefore to identify gene expression signatures for AMR and acute cellular rejection in heart transplantation and 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 FFPE-EMB
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None