Biomarkers for Diagnosis, Prognosis, and Targeted Therapy After Heart Transplantation

Recruiting

• Conditions: Heart Transplant Rejection
• Interventions: Diagnostic Test: Cell-free DNA

• Registration Number: NCT06064123
• Lead Sponsor: Helsinki University Central Hospital

Brief Summary

The objective of this prospective observational single center study is to investigate donor-derived cell-free DNA (ddcfDNA), peripheral blood platelet mRNA, peripheral blood extracellular vesicle mRNA, and peripheral blood leukocyte mRNA expression in recognition of clinically significant endomyocardial biopsy (EMB) proven acute rejection in human heart transplant recipients. In detail, the objective is to develop novel biomarkers and liquid biopsies for diagnosis, prognosis, and targeted molecular therapy for primary graft failure, ischemia-reperfusion injury, acute rejection, and development of late graft failure and cardiac allograft vasculopathy, and for monitoring immunosuppression after heart transplantation.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-22
• Study First Submitted: 2023-06-20
• Status Verified: 2023-10
• Study First Submitted QC: 2023-10-02
• Last Update Submitted: 2023-10-02
• Study First Posted: 2023-10-03
• Last Update Posted: 2023-10-03
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• patient age > 18 years
• heart transplant recipient
• has signed informed consent

Exclusion Criteria

• foreign residency
• no signed informed consent collected

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cardiac transplant recipients	Cell-free DNA	The group consist of all recruited cardiac transplant recipients operated in Helsinki University Hospital

Primary Outcome Measures

Name	Time	Method
Plasma donor-derived cell-free DNA (dd-cfDNA) for routine surveillance of acute rejection after heart transplantation	5 years	To compare plasma dd-cfDNA to endomyocardial biopsy data
Allograft educated platelet-derived mRNA for gene expression profiling of acute rejection after heart transplantation	5 years	To compare gene expression profile of allograft-educated platelets to endomyocardial biopsy data
Plasma extracellular vesicle (EV) derived mRNA for gene expression profiling of acute rejection after heart transplantation	5 years	To compare gene expression profile of EV-derived mRNA to endomyocardial biopsy data
Plasma glycoproteins for routine surveillance of acute rejection after heart transplantation	5 years	To compare plasma glycoproteome profile to endomyocardial biopsy data

Secondary Outcome Measures

Name	Time	Method
Plasma metabolomics changes during acute rejection after heart transplantation	1 year	Plasma metabolic changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation to investigate if there are any plasma metabolomics changes during different grades of acute rejection.
Plasma metabolomics changes during the first year after heart transplantation and their relationship to the development of cardiac allograft vasculopathy	5 years	Plasma metabolomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation and their relationship to the development of cardiac allograft vasculopathy in coronary angiogram will be investigated at 1, 3, and 5 years.
Plasma proteomics changes during acute rejection after heart transplantation	1 year	Plasma proteomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation to investigate if there are any plasma proteomics changes during different grades of acute rejection during the first year.
Peripheral blood mononuclear cell mRNA expression for gene expression profiling of acute rejection after heart transplantation	1 year	To compare gene expression profile of peripheral blood mononuclear cells to endomyocardial biopsy data
Plasma metabolomics changes during the first year after heart transplantation and their relationship to patient survival at 1, 3, and 5 years	5 years	Plasma metabolomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation and their relationship to patient survival will be investigated at 1, 3, and 5 years.
Plasma proteomics changes during the first year after heart transplantation and their relationship to the development of cardiac allograft vasculopathy	5 years	Plasma proteomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation and their relationship to the development of cardiac allograft vasculopathy in coronary angiogram will be investigated at 1, 3, and 5 years.
Plasma proteomics changes during the first year after heart transplantation and their relationship to patient survival at 1, 3, and 5 years	5 years	Plasma proteomics changes will be measured by mass spectrometry during routine surveillance endomyocardial biopsies taken at 2, 4, 6, 8, and 12 weeks and at 4, 5, 6, 8, 10, and 12 months after heart transplantation and and their relationship to patient survival will be investigated at 1, 3, and 5 years.

Trial Locations

Locations (1)

Helsinki University Hospital; 🇫🇮 Helsinki, Uusimaa, Finland