Unraveling Mechanism of Action of Extracorporeal Photopheresis in Heart and Lung Transplant Patients (URRAH)

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.

Study Overview

• Status: Completed
• Conditions: Cardiac Allograft Vasculopathy; Chronic Lung Allograft Dysfunction (CLAD); Heart Transplanted Patients; Lung Transplanted Patients

Detailed Description

The primary objective of the present study is to identify the biomarkers associated to response to ECP after 6 months of treatment.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• Italy
  • Pavia, Italy, 27100
    • Fondazione IRCCS Policlinico San Matteo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Heart and lung transplant patients who receive diagnosis of chronic lung allograft dysfunction (CLAD) or cardiac allograft vasculopathy (CAV)

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Lung transplanted patients who receive diagnosis of chronic lung allograft dysfunction (CLAD)
Heart transplanted patients who receive diagnosis of cardiac allograft vasculopathy (CAV)

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	After 2 years of follow-up from ECP
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

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Actual): July 31, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: March 21, 2025
• First Submitted That Met QC Criteria: March 21, 2025
• First Posted (Actual): March 28, 2025

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: ECP, heart and lung rejection, miRNA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases
• Other Study ID Numbers: URRAH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No