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

NCT06064123 | Unknown

• 1 other identifier: HUS/3654/2017
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Transplant Rejection

Keywords

Donor-derived Cell-Free DNA; Platelet; Endomyocardial biopsy; Liquid biopsy; Transcriptome; Proteomics; Metabolomics; Glycoproteins; Surveillance; Extracellular Vesicles

Outcome Measures

Primary Outcomes (4)

• Plasma donor-derived cell-free DNA (dd-cfDNA) for routine surveillance of acute rejection after heart transplantation

  To compare plasma dd-cfDNA to endomyocardial biopsy data

  5 years

• Allograft educated platelet-derived mRNA for gene expression profiling of acute rejection after heart transplantation

  To compare gene expression profile of allograft-educated platelets to endomyocardial biopsy data

  5 years

• Plasma extracellular vesicle (EV) derived mRNA for gene expression profiling of acute rejection after heart transplantation

  To compare gene expression profile of EV-derived mRNA to endomyocardial biopsy data

  5 years

• Plasma glycoproteins for routine surveillance of acute rejection after heart transplantation

  To compare plasma glycoproteome profile to endomyocardial biopsy data

  5 years

Secondary Outcomes (7)

• Plasma metabolomics changes during acute rejection after heart transplantation

  1 year

• Plasma proteomics changes during acute rejection after heart transplantation

  1 year

• Peripheral blood mononuclear cell mRNA expression for gene expression profiling of acute rejection after heart transplantation

  1 year

• 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 during the first year after heart transplantation and their relationship to patient survival at 1, 3, and 5 years

  5 years

Study Arms (1)

Cardiac transplant recipients

The group consist of all recruited cardiac transplant recipients operated in Helsinki University Hospital

Diagnostic Test: Cell-free DNA

Interventions

Cell-free DNA DIAGNOSTIC_TEST

Donor-derived cell-free DNA relation to recipient-derived cell-free DNA is compared to histopathological rejection grade from the same time frame.

Cardiac transplant recipients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population consist of heart transplant recipients transplanted at the Helsinki University Hospital, Helsinki, Finland.

You may qualify if:

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

You may not qualify if:

• foreign residency
• no signed informed consent collected

Sponsors & Collaborators

• Helsinki University Central Hospital: lead

Study Sites (1)

Helsinki University Hospital

Helsinki, Uusimaa, 00029, Finland

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Endomyocardial biopsies, peripheral blood platelets, peripheral blood extracellular vesicles, peripheral blood leukocytes, peripheral blood plasma, peripheral blood cell-free DNA, proteomics, metabolomics, glycoproteins

MeSH Terms

Interventions

Noninvasive Prenatal Testing

Intervention Hierarchy (Ancestors)

Liquid Biopsy; Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Genetic Testing; Specimen Handling; Prenatal Diagnosis; Diagnostic Techniques, Obstetrical and Gynecological; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Karl B Lemström, MD, PhD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karl B Lemstrom, MD, PhD

CONTACT

+358504272281; Karl.Lemstrom@Hus.Fi

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiothoracic surgery

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: October 3, 2023
• Study Start: January 22, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: October 3, 2023

Record last verified: 2023-10

Locations

FI (1)