Transplant FailureLEONE-HTNCT05184426
MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT)
An observational study of Transplant Failure and Heart Transplant Rejection, run by Juan Francisco Delgado Jimenez at 3 sites in Spain.
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 Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Transplant Failure, Heart Transplant Rejection, Antibody-mediated Rejection
- What is being tested?
- Echocardiogram, Cardiac magnetic resonance and Coronary angiography
- How many people
- 90 participants
- Where
- 3 sitesSpain
- Study dates
- 1 Apr 2021to 30 Sep 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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:
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
About this study
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
Read the 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.
- Being tested
- Echocardiogram, Cardiac magnetic resonance, Coronary angiography, Endomyocardial biopsy
- Keywords
- Heart transplant, Anti-HLA antibodies, Magnetic Resonance, Echocardiogram, Transmission electron microscope
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EchocardiogramDiagnostic test
Ultrasound study to assess cardiac anatomy and function
Cardiac magnetic resonanceDiagnostic test
MR to assess cardiac anatomy, function and tissue damage
Coronary angiographyDiagnostic test
Cathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation
Endomyocardial biopsyDiagnostic test
Optic microscopy, immunofluorescence, transmission electron microscopy
| Study group | Role | What they receive |
|---|---|---|
| Exposed: Positive anti-HLA antibodies | Heart transplant patients who have developed antiHLA antibodies after transplant Receives: Diagnostic Test: Echocardiogram; Diagnostic Test: Cardiac magnetic resonance; Diagnostic Test: Coronary angiography; Diagnostic Test: Endomyocardial biopsy | |
| Non-exposed: Negative anti-HLA antibodies | Heart transplant patients without antiHLA antibodies with similar transplant date to its correspondent case. Receives: Diagnostic Test: Echocardiogram; Diagnostic Test: Cardiac magnetic resonance; Diagnostic Test: Coronary angiography; Diagnostic Test: Endomyocardial biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Histology findings with transmission electron microscopy (TEM)
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
Measured: 14 days
Histology findings with optic microscopy (OM)
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
Measured: 14 days
Histology findings with immunohistochemistry (IHQ) techniques.
Detailed description of the antibodies-mediated graft injury depending on exposition-time through a detailed evaluation
Measured: 14 days
Secondary outcomes (10)
Microvascular function (pressure guidewire)
Index of microcirculatory resistance
Measured: 14 days
Microvascular function (pressure guidewire 2)
Coronary flow reserve
Measured: 14 days
Microvascular function (cardiac magnetic resonance)
Quantitative perfusion evaluation
Measured: 14 days
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
Measured: 14 days
Myocardial fibrosis (cardiac magnetic resonance)
T1 recovery time mapping to identify remodeling and fibrosis secondary to microvascular damage
Measured: 14 days
Myocardial fibrosis (cardiac magnetic resonance 2)
Extracellular volumen quantification to identify remodeling and fibrosis secondary to microvascular damage
Measured: 14 days
Myocardial fibrosis (echocardiography)
Global longitudinal strain to identify remodeling and fibrosis secondary to microvascular damage
Measured: 14 days
Serum markers of fibrosis
FGF - 23, PICP, PIIINP, galectin-3, soluble-ST2 as serum/plasmatic markers of fibrosis and remodeling
Measured: 14 days
Coronary allograft vasculopathy (CAV)
Fractional flow reserve (coronary physiology) as early marker of CAV
Measured: 14 days
Coronary allograft vasculopathy (CAV 2)
Intimal thickness (intravascular ultrasound) as early marker of CAV
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2022
- Study start1 Apr 2021
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transplant FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Juan Francisco Delgado Jimenez
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
- Responsible party
- Sponsor-investigator, Juan Francisco Delgado Jimenez, Hospital Universitario 12 de Octubre
- Investigators
- Juan F Delgado, MD PhD, Study chair, University Hospital 12 de Octubre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05184426
- Sponsor's protocol ID
- LEONE-HT
- Acronym
- LEONE-HT
- Status last verified
- Jun 2022
- First submitted
- 19 Jul 2021
- Last updated
- 21 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36287047
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MuLtimodality EvaluatiOn of aNtibody mEdiated Damage in Heart Transplantation (LEONE-HT)
- ClinicalTrials.gov ID
- NCT05184426
- Acronym / sponsor ID
- LEONE-HT / LEONE-HT
- Keywords
- Heart transplant, Anti-HLA antibodies, Magnetic Resonance, Echocardiogram, Transmission electron microscope
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Juan Francisco Delgado JimenezUniversity, hospital or other
- Collaborators
- Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Sep 2029 (estimated)
- First posted
- 11 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Exposed: Positive anti-HLA antibodies | – | Diagnostic Test: Echocardiogram, Diagnostic Test: Cardiac magnetic resonance, Diagnostic Test: Coronary angiography, Diagnostic Test: Endomyocardial biopsyHeart transplant patients who have developed antiHLA antibodies after transplant |
| Non-exposed: Negative anti-HLA antibodies | – | Diagnostic Test: Echocardiogram, Diagnostic Test: Cardiac magnetic resonance, Diagnostic Test: Coronary angiography, Diagnostic Test: Endomyocardial biopsyHeart transplant patients without antiHLA antibodies with similar transplant date to its correspondent case. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- Exposed:
- Non-exposed: Heart transplant procedure contemporary to the index case with negative anti-HLA antibodies.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EchocardiogramUltrasound study to assess cardiac anatomy and function | Diagnostic test | Exposed: Positive anti-HLA antibodies, Non-exposed: Negative anti-HLA antibodies |
| Cardiac magnetic resonanceMR to assess cardiac anatomy, function and tissue damage | Diagnostic test | Exposed: Positive anti-HLA antibodies, Non-exposed: Negative anti-HLA antibodies |
| Coronary angiographyCathteterization to assess coronary anatomy. Intravascular ultrasound to obtained a detailed assessment of vessels anatomy. Guidewire pressure to assess microcirculation | Diagnostic test | Exposed: Positive anti-HLA antibodies, Non-exposed: Negative anti-HLA antibodies |
| Endomyocardial biopsyOptic microscopy, immunofluorescence, transmission electron microscopy | Diagnostic test | Exposed: Positive anti-HLA antibodies, Non-exposed: Negative anti-HLA antibodies |
Primary outcome
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
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
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
10 secondary outcomes
Microvascular function (pressure guidewire)
Time frame: 14 days
Microvascular function (pressure guidewire 2)
Time frame: 14 days
Microvascular function (cardiac magnetic resonance)
Time frame: 14 days
Increased water content (intracellular edema)
Time frame: 14 days
Myocardial fibrosis (cardiac magnetic resonance)
Time frame: 14 days
Myocardial fibrosis (cardiac magnetic resonance 2)
Time frame: 14 days
Myocardial fibrosis (echocardiography)
Time frame: 14 days
Serum markers of fibrosis
Time frame: 14 days
Coronary allograft vasculopathy (CAV)
Time frame: 14 days
Coronary allograft vasculopathy (CAV 2)
Time frame: 14 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2022.
- Derived from this study: PubMed 36287047Nuche 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan F Delgado, MD PhD study chair
University Hospital 12 de Octubre
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Transplant Failure and Heart Transplant Rejection, run by Juan Francisco Delgado Jimenez at 3 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Histology findings with transmission electron microscopy (TEM) (time frame: 14 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05184426, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2022.