Clinical trial NCT05184426: MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT)
Official title: MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Transplant Failure
Heart Transplant Rejection
Antibody-mediated Rejection
Keywords: Heart transplant
Anti-HLA antibodies
Magnetic Resonance
Echocardiogram
Transmission electron microscope
Lead sponsor: Hospital Universitario 12 de Octubre
Sponsor class: OTHER
Collaborators: name: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
First posted: 2022-01-11
Enrollment: 90
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Histology findings with transmission electron microscopy (TEM)
timeFrame: 14 days
measure: Histology findings with optic microscopy (OM)
timeFrame: 14 days
measure: Histology findings with immunohistochemistry (IHQ) techniques.
timeFrame: 14 days
Secondary outcomes:
measure: Microvascular function (pressure guidewire)
timeFrame: 14 days
measure: Microvascular function (pressure guidewire 2)
timeFrame: 14 days
measure: Microvascular function (cardiac magnetic resonance)
timeFrame: 14 days
measure: Increased water content (intracellular edema)
timeFrame: 14 days
measure: Myocardial fibrosis (cardiac magnetic resonance)
timeFrame: 14 days
measure: Myocardial fibrosis (cardiac magnetic resonance 2)
timeFrame: 14 days
measure: Myocardial fibrosis (echocardiography)
timeFrame: 14 days
measure: Serum markers of fibrosis
timeFrame: 14 days
measure: Coronary allograft vasculopathy (CAV)
timeFrame: 14 days
measure: Coronary allograft vasculopathy (CAV 2)
timeFrame: 14 days
Other outcomes:
measure: Adverse events
timeFrame: 5 years
Locations:
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
affiliation: University Hospital 12 de Octubre
name: Juan F Delgado, MD PhD
role: STUDY_CHAIR
References:
citation: Nuche J, de la Cruz Bertolo J, Marco Clement I, Sanchez VS, Sarnago Cebada F, Mancebo E, Enguita AB, Alonso-Riano M, Ruiz-Hurtado G, Lopez-Azor JC, Hernandez-Perez FJ, Castrodeza J, Sanchez Gonzalez J, Arribas Ynsaurriaga F, Garcia-Cosio Carmena MD, Delgado JF. Rationale and Protocol of the Multimodality Evaluation of Antibody-Mediated Injury in Heart Transplantation (LEONE-HT) Observational Cross-Sectional Study. Methods Protoc. 2022 Sep 25;5(5):75. doi: 10.3390/mps5050075.