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

Antibody-mediated Rejection Clinical Trial

— LEONE-HT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05184426
• Other study ID #: LEONE-HT
• Status: Active, not recruiting
• 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
• 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.

Related Conditions & MeSH terms

• Antibody-mediated Rejection
• Heart Transplant Rejection
• Transplant Failure

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