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NCT Number: NCT05184426

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

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

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Transplant Failure Antibody-mediated Rejection Heart Transplant Rejection

Sex eligibility

All sexes

Study type

Observational

Primary location

Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.
  • 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.

Treatment and study plan

Echocardiogram

Diagnostic Test

Ultrasound study to assess cardiac anatomy and function

Cardiac magnetic resonance

Diagnostic Test

MR to assess cardiac anatomy, function and tissue damage

Coronary angiography

Diagnostic Test

Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation

Endomyocardial biopsy

Diagnostic Test

Optic microscopy, immunofluorescence, transmission electron microscopy

Primary outcomes

  1. 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

  2. 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

  3. 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

Secondary outcomes

  1. Microvascular function (pressure guidewire)

    Time frame: 14 days

    Index of microcirculatory resistance

  2. Microvascular function (pressure guidewire 2)

    Time frame: 14 days

    Coronary flow reserve

  3. Microvascular function (cardiac magnetic resonance)

    Time frame: 14 days

    Quantitative perfusion evaluation

  4. 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

  5. Myocardial fibrosis (cardiac magnetic resonance)

    Time frame: 14 days

    T1 recovery time mapping to identify remodeling and fibrosis secondary to microvascular damage

  6. Myocardial fibrosis (cardiac magnetic resonance 2)

    Time frame: 14 days

    Extracellular volumen quantification to identify remodeling and fibrosis secondary to microvascular damage

  7. Myocardial fibrosis (echocardiography)

    Time frame: 14 days

    Global longitudinal strain to identify remodeling and fibrosis secondary to microvascular damage

  8. Serum markers of fibrosis

    Time frame: 14 days

    FGF - 23, PICP, PIIINP, galectin-3, soluble-ST2 as serum/plasmatic markers of fibrosis and remodeling

  9. Coronary allograft vasculopathy (CAV)

    Time frame: 14 days

    Fractional flow reserve (coronary physiology) as early marker of CAV

  10. Coronary allograft vasculopathy (CAV 2)

    Time frame: 14 days

    Intimal thickness (intravascular ultrasound) as early marker of CAV

Other outcomes

  1. Adverse events

    Time frame: 5 years

    Heart failure, re-transplant, death

Sponsors and collaborators

Lead sponsor

Juan Francisco Delgado Jimenez

Other

Collaborators

  • Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Registry information

Acronym: LEONE-HT

Important dates

Study start
2021
Primary completion
2024
Study completion
2029
First posted
Jan 11, 2022
Registry last updated
Jun 21, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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