MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT) (LEONE-HT)

June 14, 2022 updated by: Juan Francisco Delgado Jimenez
Cross-sectional evaluation of antibody mediated injury in heart transplantation patients through a multimodal approach: electron microscopy, optic microscopy, immunohistochemistry techniques, transthoracic echocardiography, cardiac magnetic resonance, pressure guide wire, intravascular ultrasound

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Heart transplant survival has barely improved in the last decades and unsatisfactory for a large proportion of heart transplant recipients. The development of leukocyte antigen antibodies (anti-HLA) in the post-transplant patient is associated to the main causes of graft dysfunction. The mechanisms of this damage are unclear and there's no effective treatment.

The investigators aim is to identify early markers of graft injury through a complete morphological and functional evaluation with histological analysis, immunological assays, advanced imaging techniques and invasive evaluation of coronary vasculature in patients with anti-HLA compared to matching controls.

The investigators propose a cross-sectional study within a large heart transplant cohort. This is a multicentric observational multimodal study. The investigators aim is to establish early characteristics of antibody mediated damage and set the bases for future studies looking for new treatment targets.

Study Type

Observational

Enrollment (Anticipated)

90

Contacts and Locations

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

Study Locations

  • Spain
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de octubre
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Maranon
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro Majadahonda

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
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population will be conformed of heart transplant patients who are under follow-up at 3 hospitals of the Autonomous Region of Madrid (Spain). All the three hospitals are national referral center for heart transplantation.

Description

Inclusion Criteria:

  1. Exposed:

    • Heart transplant recipients

    • "De novo" antiHLA detection (after heart transplant):

      • Mean fluorescence intensity (MFI)) > 2000 for donor-specific antibodies
      • Standard fluorescence intensity (SFI) > 150 000 for non-donor specific antibodies

    • Detailed immunological history:

      • Determination of anti-HLA antibodies before heart transplant.
      • Serial determination of anti-HLA antibodies during heart transplantation follow-up
    • Known HLA typing of the donor.
  2. Non-exposed: Heart transplant procedure contemporary to the index case with negative anti-HLA antibodies.

Exclusion Criteria:

  • Recipient of a second HT
  • Multiple organ transplantation
  • Unknown immunological history
  • Recipients sensitized with anti-HLA antibodies against donor's HLA before the transplant
  • CMR contrast will not be administered in patients with glomerular filtration rate < 30 ml/kg/1.73m2
  • Patients with implanted cardiac devices or any other magnetic resonance non-compatible metallic prosthetic material will not undergo CMR.

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

  • Observational Models: Cohort
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Exposed: Positive anti-HLA antibodies
Heart transplant patients who have developed antiHLA antibodies after transplant
Diagnostic test: Echocardiogram
Ultrasound study to assess cardiac anatomy and function
Diagnostic test: Cardiac magnetic resonance
MR to assess cardiac anatomy, function and tissue damage
Diagnostic test: Coronary angiography
Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation
Diagnostic test: Endomyocardial biopsy
Optic microscopy, immunofluorescence, transmission electron microscopy
Non-exposed: Negative anti-HLA antibodies
Heart transplant patients without antiHLA antibodies with similar transplant date to its correspondent case.
Diagnostic test: Echocardiogram
Ultrasound study to assess cardiac anatomy and function
Diagnostic test: Cardiac magnetic resonance
MR to assess cardiac anatomy, function and tissue damage
Diagnostic test: Coronary angiography
Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation
Diagnostic test: Endomyocardial biopsy
Optic microscopy, immunofluorescence, transmission electron microscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histology findings with transmission electron microscopy (TEM)
Time Frame: 14 days
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
14 days
Histology findings with optic microscopy (OM)
Time Frame: 14 days
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
14 days
Histology findings with immunohistochemistry (IHQ) techniques.
Time Frame: 14 days
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microvascular function (pressure guidewire)
Time Frame: 14 days
Index of microcirculatory resistance
14 days
Microvascular function (pressure guidewire 2)
Time Frame: 14 days
Coronary flow reserve
14 days
Microvascular function (cardiac magnetic resonance)
Time Frame: 14 days
Quantitative perfusion evaluation
14 days
Increased water content (intracellular edema)
Time Frame: 14 days
T2 recovery times mapping (cardiac magnetic resonance) to detect intracellular edema (endothelial vacuolization) as an early sign of microvascular damage
14 days
Myocardial fibrosis (cardiac magnetic resonance)
Time Frame: 14 days
T1 recovery time mapping to identify remodeling and fibrosis secondary to microvascular damage
14 days
Myocardial fibrosis (cardiac magnetic resonance 2)
Time Frame: 14 days
Extracellular volumen quantification to identify remodeling and fibrosis secondary to microvascular damage
14 days
Myocardial fibrosis (echocardiography)
Time Frame: 14 days
Global longitudinal strain to identify remodeling and fibrosis secondary to microvascular damage
14 days
Serum markers of fibrosis
Time Frame: 14 days
FGF - 23, PICP, PIIINP, galectin-3, soluble-ST2 as serum/plasmatic markers of fibrosis and remodeling
14 days
Coronary allograft vasculopathy (CAV)
Time Frame: 14 days
Fractional flow reserve (coronary physiology) as early marker of CAV
14 days
Coronary allograft vasculopathy (CAV 2)
Time Frame: 14 days
Intimal thickness (intravascular ultrasound) as early marker of CAV
14 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: 5 years
Heart failure, re-transplant, death
5 years

Collaborators and Investigators

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

Sponsor

Juan Francisco Delgado Jimenez

Collaborators

Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Investigators

  • Study Chair: Juan F Delgado, MD PhD, University Hospital 12 de Octubre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

April 1, 2021

Primary Completion (Anticipated)

September 30, 2024

Study Completion (Anticipated)

September 30, 2029

Study Registration Dates

First Submitted

July 19, 2021

First Submitted That Met QC Criteria

December 21, 2021

First Posted (Actual)

January 11, 2022

Study Record Updates

Last Update Posted (Actual)

June 21, 2022

Last Update Submitted That Met QC Criteria

June 14, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • LEONE-HT

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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