Clinical trial NCT06899828: Unraveling Mechanism of Action of Extracorporeal Photopheresis in Heart and Lung Transplant Patients
Official title: Unraveling Mechanism of Action of Extracorporeal Photopheresis in Heart and Lung Transplant Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Transplanted Patients
Lung Transplanted Patients
Chronic Lung Allograft Dysfunction (CLAD)
Cardiac Allograft Vasculopathy
Keywords: ECP, heart and lung rejection, miRNA
Lead sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
Sponsor class: OTHER
First posted: 2025-03-28
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

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.

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: After 6 months from ECP treatment
Secondary outcomes:
measure: 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)
timeFrame: After 6 months of therapy
measure: Evaluation the effectiveness of ECP
timeFrame: After 2 years of follow-up from ECP
measure: Effect of ECP on progression of myocardial fibrosis evaluated at CMR
timeFrame: After 6 months of treatment
measure: Effect of ECP on ventricular function evaluated at echocardiography
timeFrame: After 6 months of treatment
measure: Trend of heart failure biomarkers (NT proBNP or BNP) after 6 months of treatment
timeFrame: After 6 months of treatment
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
Study officials:
References: