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

NCT06899828 | Completed

• 1 other identifier: URRAH
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Transplanted Patients; Lung Transplanted Patients; Chronic Lung Allograft Dysfunction (CLAD); Cardiac Allograft Vasculopathy

Keywords

ECP, heart and lung rejection, miRNA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

• 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

Study Arms (2)

Lung transplanted patients who receive diagnosis of chronic lung allograft dysfunction (CLAD)

Heart transplanted patients who receive diagnosis of cardiac allograft vasculopathy (CAV)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, Pavia, 27100, Italy

Location

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: March 28, 2025
• Study Start: April 17, 2023
• Primary Completion: July 31, 2024
• Study Completion: July 31, 2024
• Last Updated: March 28, 2025

Record last verified: 2025-02

Locations

IT (1)