Cardiac Allograft Vasculopathy, Chronic Lung Allograft Dysfunction (CLAD), Heart Transplanted Patients, Lung Transplanted Patients
Conditions
Keywords
ECP, heart and lung rejection, miRNA
Brief summary
This is a prospective observational single center national study. Lung and heart transplant patients with a definite diagnosis of chronic lung allograft dysfunction (CLAD) or cardiac allograft vasculopathy (CAV) will be assigned for extracorporeal photopheresis (ECP) as per common clinical practice to a 6-month ECP cycle with the aim of limiting progression of organ dysfunction. The exact mechanisms of ECP in chronic rejection after lung and heart transplantation (CLAD and CAV) are elusive but it is thought to induce apoptosis of lymphocytes and to generate regulatory T cells, which modulate transplant immune rejection by a complex effect.
Detailed description
The primary objective of the present study is to identify the biomarkers associated to response to ECP after 6 months of treatment.
Interventions
None listed
Sponsors
Fondazione IRCCS Policlinico San Matteo di Pavia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Lung transplanted patients will be enrolled according to current per center protocol at diagnosis of established CLAD grade 1-2 (diagnosis will be made according to published guidelines) . Rate of graft function decline will be classified as rapid (\>/= 100 ml/month) or slow (\< 100ml/month) during the 6 months preceding ECP treatment. All patients will be diagnosed as CLAD after a failure of a 3-month trial with azithromycin. They will be enrolled in ECP treatment at CLAD grade 1-2. ECP response will be assessed after 6 months of treatment and patients experiencing \> 10% decline with respect to baseline value at ECP initiation in graft function will be classified as non-responders.Heart transplanted patients with demonstrated CAV in a recent angiography (\<6 months) in absence of acute cellular or antibodies mediated rejection at myocardial biopsy, will be enrolled The diagnosis of CAV will require the presence of thickening of the arterial intima in any epicardial artery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| identification the primary mechanism of action of ECP in CLAD and CAV by analyzing biological markers (such as relative expression levels of microRNAs, potentially involved in immune regulation), associated to response to a 6 month-ECP treatment course | After 6 months from ECP treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between up-regulation or down-regulation of miRNAs at 6 months of therapy respect to baseline and other immune variables (regulatory T cells activation and differentiation, inflammatory cytokines levels and presence of anti-HLA antibodies) | After 6 months of therapy | — |
| Evaluation the effectiveness of ECP | After 2 years of follow-up from ECP | Evaluation the effectiveness of ECP in reducing cardiovascular mortality and preventing percutaneous myocardial revascularization and hospitalization by cardiovascular causes at 2 years of follow-up in comparison to a control population of heart transplant recipients with CAV included in our historical archive |
| Effect of ECP on progression of myocardial fibrosis evaluated at CMR | After 6 months of treatment | — |
| Effect of ECP on ventricular function evaluated at echocardiography | After 6 months of treatment | — |
| Trend of heart failure biomarkers (NT proBNP or BNP) after 6 months of treatment | After 6 months of treatment | — |
Countries
Italy
Outcome results
None listed