Lung Transplant RejectionILTRANCT06302556
The Role of Immune Checkpoints in Lung Transplant (ILTRA)
An observational study of Lung Transplant Rejection, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 4 sites in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Lung Transplant Rejection
- What is being tested?
- Immune checkpoints analysis and Gene expression analysis
- How many people
- 280 participants
- Where
- 4 sitesItaly
- Study dates
- Apr 2024to Feb 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- Lung transplant patients
Who cannot join
- Hyperimmunized patients
- History of auto-immune disorders
Trial locations and contacts
4 sites in 1 country.
Italy4 sites
Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico
Milan, 20122
Mario Nosotti, Medicine, 3393924679, mario.nosotti@unimi.it
Ilaria Righi, Medicine, +393470556707, ilaria.righi78@gmail.com
University of Modena and Reggio Emilia
Modena, 41121
Marcello Pinti, Biology, +390592055386, marcello.pinti@unimore.it
University of Padua
Padova, 35131
Marco Schiavon, Medicine, +39 3475642901, marco.schiavon@unipd.it
University of Turin
Torino, 10124
Massimo Boffini, Medicine, +39 3474267034, massimo.boffini@unito.it
About this study
Official title: The Role of Immune Checkpoints in Lung Transplant: the Pathways of Rejection and the Immunomodulatory Therapeutic Perspectives
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.
Read the 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).
- Conditions
- Lung Transplant Rejection
- Being tested
- Immune checkpoints analysis, Gene expression analysis
- Keywords
- Lung transplantation, Immune checkpoint, Acute rejection, Chronic rejection, Chronic lung allograft dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immune checkpoints analysisDiagnostic test
The researcher will analyze immune checkpoint molecules, which will include the lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), V-domain Ig suppressor of T cell activation (VISTA), besides the canonical PD1 and ligands L1 and L2, T cell immunoglobulin and ITIM domain (TIGIT) and CTLA-4. In addition, Foxp3, GATA3 and TOX will be analyzed as specific lineage markers.
Gene expression analysisDiagnostic test
Immune cells will be purified from bronchoalveolar lavage; total RNA will be purified and subjected to gene expression analysis by Quantigene multiplex 80-plex Assay, which allows to evaluate simultaneously the follow mRNA targets: CCL2, CCL3, CCL5, CXCL10, CSF2, CSF3, IL1A, IL1B, IL1RN, IL6, IL6R, IL8, IL10, IL12B, IL17A, IL18, IL22, IL28A, TNF, TNFRSF4, IFNA2, IFNB1, IFNG, IFI16, IFITM1, IFITM3, MX1, TLR3, TLR4, TLR7, TLR8, NOD1, NOD2, CASP1, NLRP3, PYCARD, CD44, CLEC4M, CD209, ITGA4, ITGB7, CH25H, ABCA1, HMGCS1, NR1H3, ACAT1, PDCD1, PTGS2, CD274, CD69, MPO, HAVCR2, TAP1, ERAP1, ERAP2, AGTR2, AGTR1, PPARG, CRP, IL7, IL12A, ACE2, ELOVL6, CD38, NOS2
| Study group | Role | What they receive |
|---|---|---|
| Lung re-transplant cohort | This cohort includes consecutive participants who underwent lung re-transplantation for chronic lung allograft dysfunction from 2010 to 2020; the immune checkpoints analyses will be conducted on stored specimens from lungs explanted during re-transplantation. Receives: Diagnostic Test: Immune checkpoints analysis | |
| Previous lung transplant cohort | This cohort includes participants who received first bilateral lung transplantation from 2017 to 2020. The immune checkpoints analyses will be conducted on stored specimens from postoperative transbronchial biopsy performed for clinical suspicious of rejection. Receives: Diagnostic Test: Immune checkpoints analysis | |
| Prospective lung transplant cohort | This cohort includes participants who will have their first bilateral lung transplant from April 2024 to April 2025. Immunopathological characterization of bronchoalveolar leukocytes and analysis of immuno checkpoints will be performed on leftover material of bronchoalveolar lavage and transbronchial lung biopsy samples performed for clinical suspicious of rejection. Receives: Diagnostic Test: Immune checkpoints analysis; Diagnostic Test: Gene expression analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lung-tissue immune-checkpoint profile and bronchoalveolar immune-cells mRNA signature in acute rejection after lung transplantation.
Prevalence of immune checkpoint markers and gene-expression on leukocytes from transbronchial biopsies and bronchoalveolar lavage. Participants: cohort number 3.
Measured: Twelve months after lung transplantation (prospective data)
Lung-tissue immune-checkpoint profile in chronic rejection after lung transplantation.
Prevalence of immune checkpoint markers on leukocytes from explanted lung grafts and transbronchial biopsies. Participants: cohort number 1 and 2.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2024
- Study startApr 2024 (estimated)
- Primary completionJan 2026 (estimated)
- Study completionFeb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lung Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 280 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- University of Milan, University of Padova, University of Turin, Italy
- Responsible party
- Sponsor
- Investigators
- Mario Nosotti, Medicine, Principal investigator, University of Milan, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06302556
- Sponsor's protocol ID
- 2022XJ9W4F
- Other IDs
- G53D2300526 0006
- Acronym
- ILTRA
- Status last verified
- Feb 2024
- First submitted
- 28 Feb 2024
- Last updated
- 8 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The anonymized data collected will be recorded on a database available online by other researchers upon request
Publications
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.
PubMed 36703976Righi 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.
PubMed 34489963Palleschi 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.
PubMed 32548241
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Immune Checkpoints in Lung Transplant: the Pathways of Rejection and the Immunomodulatory Therapeutic Perspectives
- ClinicalTrials.gov ID
- NCT06302556
- Acronym / sponsor ID
- ILTRA / 2022XJ9W4F
- Conditions
- Lung Transplant Rejection
- Keywords
- Lung transplantation, Immune checkpoint, Acute rejection, Chronic rejection, Chronic lung allograft dysfunction
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 280 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Collaborators
- University of Milan, University of Padova, University of Turin, Italy
- Study start
- Apr 2024 (estimated)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Feb 2026 (estimated)
- First posted
- 8 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lung re-transplant cohort | – | Diagnostic Test: Immune checkpoints analysisThis cohort includes consecutive participants who underwent lung re-transplantation for chronic lung allograft dysfunction from 2010 to 2020; the immune checkpoints analyses will be conducted on stored specimens from lungs explanted during re-transplantation. |
| Previous lung transplant cohort | – | Diagnostic Test: Immune checkpoints analysisThis cohort includes participants who received first bilateral lung transplantation from 2017 to 2020. The immune checkpoints analyses will be conducted on stored specimens from postoperative transbronchial biopsy performed for clinical suspicious of rejection. |
| Prospective lung transplant cohort | – | Diagnostic Test: Immune checkpoints analysis, Diagnostic Test: Gene expression analysisThis cohort includes participants who will have their first bilateral lung transplant from April 2024 to April 2025. Immunopathological characterization of bronchoalveolar leukocytes and analysis of immuno checkpoints will be performed on leftover material of bronchoalveolar lavage and transbronchial lung biopsy samples performed for clinical suspicious of rejection. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- Lung transplant patients
Key exclusion criteria (2 listed)
- Hyperimmunized patients
- History of auto-immune disorders
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immune checkpoints analysisThe researcher will analyze immune checkpoint molecules, which will include the lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), V-domain Ig suppressor of T cell activation (VISTA), besides the canonical PD1 and ligands L1 and L2, T cell immunoglobulin and ITIM domain (TIGIT) and CTLA-4. In addition, Foxp3, GATA3 and TOX will be analyzed as specific lineage markers. | Diagnostic test | Lung re-transplant cohort, Previous lung transplant cohort, Prospective lung transplant cohort |
| Gene expression analysisImmune cells will be purified from bronchoalveolar lavage; total RNA will be purified and subjected to gene expression analysis by Quantigene multiplex 80-plex Assay, which allows to evaluate simultaneously the follow mRNA targets: CCL2, CCL3, CCL5, CXCL10, CSF2, CSF3, IL1A, IL1B, IL1RN, IL6, IL6R, IL8, IL10, IL12B, IL17A, IL18, IL22, IL28A, TNF, TNFRSF4, IFNA2, IFNB1, IFNG, IFI16, IFITM1, IFITM3, MX1, TLR3, TLR4, TLR7, TLR8, NOD1, NOD2, CASP1, NLRP3, PYCARD, CD44, CLEC4M, CD209, ITGA4, ITGB7, CH25H, ABCA1, HMGCS1, NR1H3, ACAT1, PDCD1, PTGS2, CD274, CD69, MPO, HAVCR2, TAP1, ERAP1, ERAP2, AGTR2, AGTR1, PPARG, CRP, IL7, IL12A, ACE2, ELOVL6, CD38, NOS2 | Diagnostic test | Prospective lung transplant cohort |
Primary outcome
Lung-tissue immune-checkpoint profile and bronchoalveolar immune-cells mRNA signature in acute rejection after lung transplantation.
Time frame: Twelve months after lung transplantation (prospective data)
Prevalence of immune checkpoint markers and gene-expression on leukocytes from transbronchial biopsies and bronchoalveolar lavage. Participants: cohort number 3.
Lung-tissue immune-checkpoint profile in chronic rejection after lung transplantation.
Time frame: 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)
Prevalence of immune checkpoint markers on leukocytes from explanted lung grafts and transbronchial biopsies. Participants: cohort number 1 and 2.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
- Background: PubMed 36703976Righi 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.
- Background: PubMed 34489963Righi 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.
- Background: PubMed 32548241Palleschi 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.
- Individual participant dataSharing planned: Yes. The anonymized data collected will be recorded on a database available online by other researchers upon request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mario Nosotti, Medicine principal investigator
University of Milan, Italy
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lung Transplant Rejection, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 4 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mario Nosotti, Medicine (3393924679, mario.nosotti@unimi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lung-tissue immune-checkpoint profile and bronchoalveolar immune-cells mRNA signature in acute rejection after lung transplantation. (time frame: Twelve months after lung transplantation (prospective data)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06302556, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.