Search for Noninvasive Markers of "Graft Injury" in Pediatric and Adult Patients With Congenital Heart Disease Undergoing Cardiac Transplantation

January 14, 2025 updated by: IRCCS Azienda Ospedaliero-Universitaria di Bologna
This clinical tissue-based, drug-free, single-center, longitudinal study aims to validate a new diagnostic method, namely, to evaluate whether plasma levels of circulating donor free DNA in the recipient's blood (Dd-cfDNA: donor-derived cell free DNA), in patients undergoing orthotopic heart transplantation, can be predictive of the presence of acute myocardial rejection with the same sensitivity as immunohistochemical analysis on endomyocardial biopsy specimen, the current gold standard for the diagnosis of acute cell-mediated myocardial rejection, in a population consisting of pediatric patients and adult patients with congenital heart disease undergoing orthotopic heart transplantation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

To achieve the study objective, approximately 20 patients of all ages, both pediatric and adult with congenital heart disease and undergoing orthotopic heart transplantation, followed at our center will be enrolled. Whenever a patient enrolled in the study undergoes endomyocardial biopsy, either as part of surveillance of acute myocardial rejection or for clinical suspicion of rejection, concomitantly a blood sample will be taken and analyzed for the presence of dd-cfDNA. In patients with biopsy evidence of acute rejection, a new dd-cfDNA sampling will be performed approximately three months after treatment at the next clinical follow-up. The data collected for each patient will be both baseline anthropometric data and imaging and laboratory variables collected in the normal follow-up provided by clinical practice, as well as data related to the endomyocardial biopsy result and those related to blood sampling for donor DNA.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • IRCCS Azienda Ospedaliero-Universitaria di Bologna
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients with congenital heart disease undergoing cardiac transplantation at our center or other centers, followed in follow-up at our center (Unit of Pediatric Cardiology and Developmental Age, IRCCS Azienda Ospedaliero-Universitaria di Bologna)
  • Pediatric patients undergoing cardiac transplantation at our center or other centers but followed in follow-up at our center
  • Obtaining informed consent from the adult patient or parent/guardian in case of minor

Exclusion Criteria:

  • Failure to obtain informed consent from the adult patient or parent/guardian in case of minor

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Endomyocardial biopsy and analysis for the presence of dd-cfDNA
Whenever a patient enrolled in the study undergoes endomyocardial biopsy, either as part of surveillance of acute myocardial rejection or for clinical suspicion of rejection, concomitantly a blood sample will be taken and analyzed for the presence of dd-cfDNA. In patients with biopsy evidence of acute rejection, a new dd-cfDNA sampling will be performed approximately three months after treatment at the next clinical follow-up
Genetic: Evaluation of circulating donor free DNA in the recipient's blood (Dd-cfDNA: donor-derived cell free DNA)
From the blood samples taken, 2 mL of plasma separated from blood will be stored in EDTA frozen at -80°C. This material will later be processed by NGS run using of CareDX kits. The result will be provided by dedicated software as percentage of donor DNA in relation to recipient DNA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of plasma levels of circulating dd-cfDNA in the recipient's blood
Time Frame: 1 day
The primary aim of this study is to determine whether plasma levels of circulating dd-cfDNA in the recipient's blood can be predictive of the presence of acute myocardial rejection with the same sensitivity as the gold standard represented by immunohistochemical analysis on biopsy specimen. The presence of acute myocardial rejection is defined in accordance with the 2004 ISHLT guidelines as a finding at endomyocardial biopsy of cellulomediated rejection (grade 2R or 3R) and/or humoral rejection (pAMR grade 1,2 or 3), while dd-cfDNA levels, expressed as a percentage relative to the recipient's DNA, will be assessed as pathological both based on the indications in the literature for other forms of rejection (>1%), and as a continuous scale to determine a possible specific cutoff value for our population.
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Investigators

  • Principal Investigator: Luca Ragni, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 8, 2023

Primary Completion (Estimated)

November 8, 2025

Study Completion (Estimated)

March 7, 2026

Study Registration Dates

First Submitted

December 30, 2024

First Submitted That Met QC Criteria

January 14, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 14, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PED-TRANSPLANT-DNA
  • RC2022 (Other Grant/Funding Number: Ministero della Salute)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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