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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05184426
Other study ID # LEONE-HT
Secondary ID
Status Active, not recruiting
Phase
First received
Last updated
Start date April 1, 2021
Est. completion date September 30, 2029

Study information

Verified date June 2022
Source Hospital Universitario 12 de Octubre
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 90
Est. completion date September 30, 2029
Est. primary completion date September 30, 2024
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility 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 Design


Intervention

Diagnostic Test:
Echocardiogram
Ultrasound study to assess cardiac anatomy and function
Cardiac magnetic resonance
MR to assess cardiac anatomy, function and tissue damage
Coronary angiography
Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation
Endomyocardial biopsy
Optic microscopy, immunofluorescence, transmission electron microscopy

Locations

Country Name City State
Spain Hospital General Universitario Gregorio Marañon Madrid
Spain Hospital Universitario 12 de Octubre Madrid
Spain Hospital Universitario Puerta de Hierro Majadahonda Majadahonda Madrid

Sponsors (2)

Lead Sponsor Collaborator
Juan Francisco Delgado Jimenez Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type Measure Description Time frame Safety issue
Other Adverse events Heart failure, re-transplant, death 5 years
Primary Histology findings with transmission electron microscopy (TEM) Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation 14 days
Primary Histology findings with optic microscopy (OM) Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation 14 days
Primary Histology findings with immunohistochemistry (IHQ) techniques. Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation 14 days
Secondary Microvascular function (pressure guidewire) Index of microcirculatory resistance 14 days
Secondary Microvascular function (pressure guidewire 2) Coronary flow reserve 14 days
Secondary Microvascular function (cardiac magnetic resonance) Quantitative perfusion evaluation 14 days
Secondary Increased water content (intracellular edema) T2 recovery times mapping (cardiac magnetic resonance) to detect intracellular edema (endothelial vacuolization) as an early sign of microvascular damage 14 days
Secondary Myocardial fibrosis (cardiac magnetic resonance) T1 recovery time mapping to identify remodeling and fibrosis secondary to microvascular damage 14 days
Secondary Myocardial fibrosis (cardiac magnetic resonance 2) Extracellular volumen quantification to identify remodeling and fibrosis secondary to microvascular damage 14 days
Secondary Myocardial fibrosis (echocardiography) Global longitudinal strain to identify remodeling and fibrosis secondary to microvascular damage 14 days
Secondary Serum markers of fibrosis FGF - 23, PICP, PIIINP, galectin-3, soluble-ST2 as serum/plasmatic markers of fibrosis and remodeling 14 days
Secondary Coronary allograft vasculopathy (CAV) Fractional flow reserve (coronary physiology) as early marker of CAV 14 days
Secondary Coronary allograft vasculopathy (CAV 2) Intimal thickness (intravascular ultrasound) as early marker of CAV 14 days
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