Clinical trial NCT06302556: The Role of Immune Checkpoints in Lung Transplant (ILTRA)
Official title: The Role of Immune Checkpoints in Lung Transplant: the Pathways of Rejection and the Immunomodulatory Therapeutic Perspectives
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Lung Transplant Rejection
Keywords: Lung transplantation
Immune checkpoint
Acute rejection
Chronic rejection
Chronic lung allograft dysfunction
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: University of Milan
name: University of Padova
name: University of Turin, Italy
First posted: 2024-03-08
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cohort 1: Participants who received lung re-transplantation for chronic lung allograft dysfunction.

Cohort 2 and 3: Participants who received first lung transplantation for end stage respiratory insufficiency.

Brief summary: The goal of this observational study is to learn about rejection in lung transplantation.

The main question it aims to answer is:

• what is the role of immune checkpoints in lung transplantation? Participants will describe pathways of rejection in lung transplantation analyzing the immune checkpoints on explanted lungs as well as trans-bronchial biopsies.

Detailed description: Lung transplantation is the less common solid organ transplant performed; it is the treatment of choice for end stage lung disease. Lung transplantation is "problematic" for a number of reasons: low graft availability, high waitlist mortality and unsatisfactory survival. Acute rejection, occurring days to months after surgery, has been identified as one of the main risk factors for the development of chronic rejection: in the first five years after lung transplantation, chronic rejection is the major cause of graft failure, morbidity and mortality. A deep knowledge of the immunological scenarios associated with lung graft tolerance could allow selectively switch-off T-cells involved in the rejection process. The researches, preliminary demonstrated the central role of immunological checkpoints in the development of acute rejection and its evolution towards chronic rejection. The aim of this study is the identification of markers that could be associated with the establishment of lung graft tolerance.

The project is articulated into two parts: a retrospective and a prospective section. The retrospective section is constituted by a cross-sectional study of immune checkpoints on lungs explanted during lung re-transplantation for chronic rejection (cohort 1). In addition, the retrospective section includes a retrospective cohort study of immune checkpoints on specimens from transbronchial lung biopsies of participants who received lung transplantation and have 3 years of follow-up (cohort 2). The prospective section is a cohort study of immune checkpoints on specimens from transbronchial lung biopsies and gene expression analysis on immune cells purified from bronchoalveolar lavage; participants will be subjects receiving the lung transplantation during the first year of recruitment and followed for one year (cohort 3).

Eligibility criteria: Inclusion Criteria:

* Lung transplant patients

Exclusion Criteria:

* Hyperimmunized patients
* History of auto-immune disorders

Primary outcomes:
measure: Lung-tissue immune-checkpoint profile and bronchoalveolar immune-cells mRNA signature in acute rejection after lung transplantation.
timeFrame: Twelve months after lung transplantation (prospective data)
measure: Lung-tissue immune-checkpoint profile in chronic rejection after lung transplantation.
timeFrame: Cohort 1: at re-transplantation for chronic lung allograft dysfunction (cross-sectional data). Cohort 2: from one to 36 months after lung transplantation (retrospective data)
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: University of Modena and Reggio Emilia
city: Padova
country: Italy
facility: University of Padua
city: Torino
country: Italy
facility: University of Turin
Study officials:
affiliation: University of Milan, Italy
name: Mario Nosotti, Medicine
role: PRINCIPAL_INVESTIGATOR
References:
citation: Righi I, Vaira V, Morlacchi LC, Croci GA, Rossetti V, Blasi F, Ferrero S, Nosotti M, Rosso L, Clerici M. PD-1 expression in transbronchial biopsies of lung transplant recipients is a possible early predictor of rejection. Front Immunol. 2023 Jan 10;13:1024021. doi: 10.3389/fimmu.2022.1024021. eCollection 2022.
citation: Righi I, Vaira V, Morlacchi LC, Croci GA, Rossetti V, Blasi F, Ferrero S, Nosotti M, Rosso L, Clerici M. Immune Checkpoints Expression in Chronic Lung Allograft Rejection. Front Immunol. 2021 Aug 13;12:714132. doi: 10.3389/fimmu.2021.714132. eCollection 2021.
citation: Palleschi A, Gaudioso G, Edefonti V, Musso V, Terrasi A, Ambrogi F, Franzi S, Rosso L, Tarsia P, Morlacchi LC, Ferrero S, Nosotti M, Vaira V. Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome After Lung Transplantation. Transplant Direct. 2020 Apr 9;6(5):e547. doi: 10.1097/TXD.0000000000000994. eCollection 2020 May.