A Prospective Randomized Trial of ECP in Subclinical AMR

Not Applicable

Recruiting

• Conditions: Antibody-mediated Rejection; Lung Transplant Rejection
• Interventions: Procedure: Extracorporeal Photopheresis

• Registration Number: NCT06112951
• Lead Sponsor: Medical University of Vienna

Brief Summary

The goal of this clinical trial is to evaluate the therapeutic effect of extracorporeal photopheresis in subclinical antibody-mediated rejection after lung transplantation.The main questions it aims to answer are:

1. Does ECP therapy result in a significant reduction in MFI (Mean Fluorescence Intensity) from the baseline MFI in clinically stable patients with persistent (\>6 months) dnDSAs (MFI\>1000)?

2. What is the impact of ECP therapy on the following outcomes in these patients: ACR, clinical AMR, CLAD, infections, drop-out rate, survival, adverse events?

Participants will be randomized into two groups. Each group will include 40 patients. The control group will be observed and no active treatment will be administered. The treatment group will receive extracorporeal photopheresis. First, a two-day treatment cycle will be performed once every second week for the first two months. Then, a two-day treatment cycle will be performed once a month for 6 months.

Researchers will compare the two groups regarding: MFI value, development of ACR, clinical AMR, CLAD, infections, survival, adverse events, immunophenotyping, miRNA expression profiling, cytokine expression, gene expression signature of PBMCs and proteomic characterization.

Detailed Description

Donor-specific antibodies (DSA) and antibody-mediated rejection have gained significant attention recently due to their serious consequences, but there are limited effective treatments for persistent DSAs in patients without graft dysfunction due to their associated severe side effects. Our center demonstrated that extracorporeal photopheresis (ECP) can potentially reduce the mean fluorescence intensity of dnDSAs in recipients with antibody-mediated rejection (AMR), suggesting it as a safe option for treating subclinical AMR with dnDSAs and inducing tolerogenic immunomodulation in this complex population.

The hypothesis underlying the proposed randomized controlled trial is that ECP might have the potential to reduce the burden of de novo donor-specific antibodies after lung transplantation, by modulating host humoral alloresponse and promoting tolerance, without provoking side effects.

Our primary objective is to evaluate the therapeutic effect of ECP in terms of reduction of dnDSAs titer in clinically stable patients with persistent (\>6 months) dnDSAs (MFI\>1000). As secondary objective, we intend to assess the therapeutic effect of ECP on incidence of clinical AMR, ACR, CLAD, survival and occurrence of infectious complications as well as the rate of adverse effects. Our experimental objectives are to provide an in-depth analysis of the immunological effects of ECP.

80 patients with persistent dnDSAs (\> 3 months) with a MFI \> 1000 will be randomized into two groups. Each group will include 40 patients. Patients will be stratified according to the presence of HLA-DQ. The control group will be observed and no active treatment will be administered. This is our standard of care in the studied clinical situation. Treatment group will receive extracorporeal photopheresis. First, a two-day treatment cycle will be performed once every second week for the first two months. Then, a two-day treatment cycle will be performed once a month for 6 months. To elucidate the specific mechanisms of ECP in modulating humoral alloresponse, a series of studies are planned: 1) flow cytometric immunophenotyping, 2) miRNA expression profiling, 3) cytokine expression, 4) gene expression signature of PBMCs, 5) proteomic characterization.

The proposed study aims to address this clinical need by investigating the effects of a safe therapeutic modality such as ECP. This study may have a dual benefit: first, it may reduce the burden of dnDSAs in lung transplant recipients, thereby reducing the incidence of antibody-mediated rejection, and second, it may promote host tolerance to the graft. In addition, we will investigate the immunomodulatory mechanisms of ECP in the context of humoral allogeneic response, which has not been previously investigated.

Study Timeline

• Study First Submitted: 2023-10-09
• Study First Submitted QC: 2023-10-30
• Study First Posted: 2023-11-02
• Study Start: 2024-03-01
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-08
• Last Update Posted: 2024-07-09
• Primary Completion: 2027-03-01
• Study Completion: 2027-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Bilateral lung transplantation
• dnDSAs > 3 months with a MFI > 1000
• No signs of allograft dysfunction
• Alemtuzumab induction therapy

Exclusion Criteria

• Inclusion in other studies
• Retransplantation
• Multi-organ transplantation
• > 12 months after transplantation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group	Extracorporeal Photopheresis	Treatment group will receive extracorporeal photopheresis. First, a two-day treatment cycle will be performed once every second week for the first two months. Then, a two-day treatment cycle will be performed once a month for 6 months.

Primary Outcome Measures

Name	Time	Method
Reduction of dnDSA titer from baseline MFI	6 months	Difference of MFI values at the start and at the end of the six month period

Secondary Outcome Measures

Name	Time	Method
Incidence of clinical AMR, ACR, CLAD, survival, infectious complications, adverse effects	6 months	Incidence of clinical AMR, ACR, CLAD, survival, infectious complications, adverse effects

Trial Locations

Locations (7)

Copenhagen University Hospital, Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Hôpital Foch; 🇫🇷 Suresnes, France

University Hospital Center Zagreb; 🇭🇷 Zagreb, Croatia

UZ Leuven; 🇧🇪 Leuven, Belgium

Policlinico San Matteo Pavia Fondazione IRCCS; 🇮🇹 Pavia, Italy

Medical University of Vienna; 🇦🇹 Vienna, Austria

University Medical Centre Ljubljana; 🇸🇮 Ljubljana, Slovenia