Bronchiolitis Obliterans Syndrome (BOS)ELITNCT07234760
ex Vivo Study of Liposomes Loaded With Everolimus in Chronic Lung Allograft Disfunction
An observational study of Bronchiolitis Obliterans Syndrome (BOS), run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site in Italy.
Trial summary
Patients subjected to lung transplantation develop acute rejection or chronic rejection with an incidence of 45% after the first year. The major clinical phenotype of chronic rejection is bronchiolitis obliterans syndrome (BOS), which cause an establishment of chronic lung inflammation status with an aberrant… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bronchiolitis Obliterans Syndrome (BOS)
- What is being tested?
- Liposomes
- Type of treatment
- Medical device
- How many people
- 19 participants
- Where
- 1 siteItaly
- Study dates
- 19 Mar 2022to 1 Jul 2025
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: BOS affected patients
Who may be able to join
- BOS/subjected to TX patients
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Patients subjected to lung transplantation develop acute rejection or chronic rejection with an incidence of 45% after the first year. The major clinical phenotype of chronic rejection is bronchiolitis obliterans syndrome (BOS), which cause an establishment of chronic lung inflammation status with an aberrant proliferation of myofibroblasts leading to fibrotic obstruction of small airways. The therapeutic regimen available for BOS patients is still scarce and is not able to revert the disease. This project aims to design a new targeted therapy based on nanoparticles that can deliver drug directly inside lungs by aerosol administration to revert BOS.
By this project will be exploit a liposomes preparation synthesized modifying surface with hyaluronic acid (HA), the physiologic ligand of CD44, a glycoprotein overexpressed by myofibroblasts forming fibrotic lesions. These targeted liposomes are loaded with everolimus (LIP(ev)-HA400kDa), a mTOR inhibitors already used for BOS patients but with significant side effects leading to a discontinuation of therapy. Loading everolimus inside liposomes allows the administration of drug directly to the lungs and decreases its side effects.
Read more
LIP(ev)-HA400kDa will be tested on different experimental settings: in vitro, ex vivo, in vivo. This approach will allow us to have a complete observation regarding the effects and the distribution of liposomes preparation, from the modulation of their specific targeting (myofibroblasts) by in vitro experiments, the analysis of LIP(ev)-HA400kDa behavior on human lung tissues and, finally, their ability to revert BOS in animal model.
Results obtained with this project will open to a new therapeutic option for BOS affected patients, the first therapy that can revert the disease prolonging the long-term survival of patients.
Read the detailed description
LFs will be isolated from BAL of BOS-affected or subjected to TX. After isolation and culture, LFs will be incubated with LIP(ev)-HA400kDa, LIP(ev) and everolimus alone, comparing the effect to control cells. At the end of the incubation, we will collect supernatants and proteins of lysed cells. Proteins extracted will be quantified and western blot will be performed to assess the expression of collagen I, fibronectin and laminin. Regarding supernatants we will evaluate cytokines concentration, in particular: IL6, IL8, TGF-beta and IL10.
LIP-HA400kDa fluorescently labelled will be incubated onto PCLSs derived from BOS explanted lungs comparing their distribution with LIP-PEG, using confocal microscopy. Moreover, using LIP(ev)-HA400kDa, LIP(ev) and everolimus alone we will assess general toxicity on PCLSs using LDH assay and cell proliferation with Ki67 expression at different time points. We will also assess the release of cytokines involved in pro-inflammation and pro-fibrotic processes.
- Conditions
- Bronchiolitis Obliterans Syndrome (BOS)
- Being tested
- Liposomes
- Keywords
- liposome
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiposomesDevice
- LIP(ev)-HA400kDa on lung fibroblasts derived from Broncoalvealar lavage of BOS affected patients checking key elements involved in pro-fibrotic signals in order to understand if our nanovehicle could modulate process basing fibrotic lesions production.
- LIP(ev)-HA400kDa and fluorescent LIP-HA400kDa in PCLSs from explanted lungs by BOS patients in order to assess the cellular distribution of LIP-HA400kDa and the effect
| Study group | Role | What they receive |
|---|---|---|
| BOS | Not described Receives: Device: Liposomes |
What is being measured
The primary outcome is the main question the study is designed to answer.
TGF-beta's levels in BAL cells
Comparison of TGF-beta levels in BAL cells in cells alone, nanoparticles alone, nanoparticles with drug delivery, and drug alone
Measured: from 24 hours to 72 hours of treatment
Secondary outcomes (2)
cytokine's levels in BAL's cells
Compare IL6, IL8, and IL10 levels in BAL cells in the four conditions.
Measured: from 24 hours to 72 hours of treatment
cytokines and TGF-beta's levels released by PCLSs
Compare the levels of cytokines IL6, IL8, IL10, and TGF-beta released by PCLSs derived from explanted lungs and evaluate toxicity and cell proliferation.
Measured: from 24 hours to 72 hours of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2025
- Study start19 Mar 2022
- Primary completion20 Apr 2022
- Study completion1 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Bronchiolitis Obliterans Syndrome (BOS)Studies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Policlinico San Matteo di PaviaThe 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di Pavia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mirko Belliato, Fondazione IRCCS Policlinico San Matteo di Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07234760
- Sponsor's protocol ID
- ELIT
- Acronym
- ELIT
- Status last verified
- Sep 2025
- First submitted
- 22 Sep 2025
- Last updated
- 18 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kelsh SE, Girgis R, Dickinson M, McDermott JK. Everolimus Use for Intolerance or Failure of Baseline Immunosuppression in Adult Heart and Lung Transplantation. Ann Transplant. 2018 Oct 23;23:744-750. doi: 10.12659/AOT.910952.
PubMed 30348935Lopez P, Kohler S, Dimri S. Interstitial Lung Disease Associated with mTOR Inhibitors in Solid Organ Transplant Recipients: Results from a Large Phase III Clinical Trial Program of Everolimus and Review of the Literature. J Transplant. 2014;2014:305931. doi: 10.1155/2014/305931. Epub 2014 Dec 18.
PubMed 25580277Klawitter J, Nashan B, Christians U. Everolimus and sirolimus in transplantation-related but different. Expert Opin Drug Saf. 2015 Jul;14(7):1055-70. doi: 10.1517/14740338.2015.1040388. Epub 2015 Apr 26.
PubMed 25912929Chung PA, Dilling DF. Immunosuppressive strategies in lung transplantation. Ann Transl Med. 2020 Mar;8(6):409. doi: 10.21037/atm.2019.12.117.
PubMed 32355853Tissot A, Danger R, Claustre J, Magnan A, Brouard S. Early Identification of Chronic Lung Allograft Dysfunction: The Need of Biomarkers. Front Immunol. 2019 Jul 17;10:1681. doi: 10.3389/fimmu.2019.01681. eCollection 2019.
PubMed 31379869Verleden GM, Glanville AR, Lease ED, Fisher AJ, Calabrese F, Corris PA, Ensor CR, Gottlieb J, Hachem RR, Lama V, Martinu T, Neil DAH, Singer LG, Snell G, Vos R. Chronic lung allograft dysfunction: Definition, diagnostic criteria, and approaches to treatment-A consensus report from the Pulmonary Council of the ISHLT. J Heart Lung Transplant. 2019 May;38(5):493-503. doi: 10.1016/j.healun.2019.03.009. Epub 2019 Apr 3. No abstract available.
PubMed 30962148Mrad A, Chakraborty RK. Lung Transplant Rejection. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK564391/
PubMed 33232061
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ex Vivo Study of Liposomes Loaded With Everolimus in Chronic Lung Allograft Disfunction
- ClinicalTrials.gov ID
- NCT07234760
- Acronym / sponsor ID
- ELIT / ELIT
- Conditions
- Bronchiolitis Obliterans Syndrome (BOS)
- Keywords
- liposome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Fondazione IRCCS Policlinico San Matteo di PaviaUniversity, hospital or other
- Study start
- 19 Mar 2022 (actual)
- Primary completion
- 20 Apr 2022 (actual)
- Study completion
- 1 Jul 2025 (actual)
- First posted
- 18 Nov 2025 (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.
Patients subjected to lung transplantation develop acute rejection or chronic rejection with an incidence of 45% after the first year. The major clinical phenotype of chronic rejection is bronchiolitis obliterans syndrome (BOS), which cause an establishment of chronic lung inflammation status with an aberrant proliferation of myofibroblasts leading to fibrotic obstruction of small airways. The therapeutic regimen available for BOS patients is still scarce and is not able to revert the disease. This project aims to design a new targeted therapy based on nanoparticles that can deliver drug directly inside lungs by aerosol administration to revert BOS.
By this project will be exploit a liposomes preparation synthesized modifying surface with hyaluronic acid (HA), the physiologic ligand of CD44, a glycoprotein overexpressed by myofibroblasts forming fibrotic lesions. These targeted liposomes are loaded with everolimus (LIP(ev)-HA400kDa), a mTOR inhibitors already used for BOS patients but with significant side effects leading to a discontinuation of therapy. Loading everolimus inside liposomes allows the administration of drug directly to the lungs and decreases its side effects.
LIP(ev)-HA400kDa will be tested on different experimental settings: in vitro, ex vivo, in vivo. This approach will allow us to have a complete observation regarding the effects and the distribution of liposomes preparation, from the modulation of their specific targeting (myofibroblasts) by in vitro experiments, the analysis of LIP(ev)-HA400kDa behavior on human lung tissues and, finally, their ability to revert BOS in animal model.
Results obtained with this project will open to a new therapeutic option for BOS affected patients, the first therapy that can revert the disease prolonging the long-term survival of patients.
Detailed description
LFs will be isolated from BAL of BOS-affected or subjected to TX. After isolation and culture, LFs will be incubated with LIP(ev)-HA400kDa, LIP(ev) and everolimus alone, comparing the effect to control cells. At the end of the incubation, we will collect supernatants and proteins of lysed cells. Proteins extracted will be quantified and western blot will be performed to assess the expression of collagen I, fibronectin and laminin. Regarding supernatants we will evaluate cytokines concentration, in particular: IL6, IL8, TGF-beta and IL10.
LIP-HA400kDa fluorescently labelled will be incubated onto PCLSs derived from BOS explanted lungs comparing their distribution with LIP-PEG, using confocal microscopy. Moreover, using LIP(ev)-HA400kDa, LIP(ev) and everolimus alone we will assess general toxicity on PCLSs using LDH assay and cell proliferation with Ki67 expression at different time points. We will also assess the release of cytokines involved in pro-inflammation and pro-fibrotic processes.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BOS | – | Device: Liposomes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- BOS affected patients
Key inclusion criteria (1 listed)
- BOS/subjected to TX patients
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Liposomes1. LIP(ev)-HA400kDa on lung fibroblasts derived from Broncoalvealar lavage of BOS affected patients checking key elements involved in pro-fibrotic signals in order to understand if our nanovehicle could modulate process basing fibrotic lesions production. 2. LIP(ev)-HA400kDa and fluorescent LIP-HA400kDa in PCLSs from explanted lungs by BOS patients in order to assess the cellular distribution of LIP-HA400kDa and the effect | Device | BOS |
Primary outcome
TGF-beta's levels in BAL cells
Time frame: from 24 hours to 72 hours of treatment
Comparison of TGF-beta levels in BAL cells in cells alone, nanoparticles alone, nanoparticles with drug delivery, and drug alone
2 secondary outcomes
cytokine's levels in BAL's cells
Time frame: from 24 hours to 72 hours of treatment
cytokines and TGF-beta's levels released by PCLSs
Time frame: from 24 hours to 72 hours of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2025.
- Background: PubMed 30348935Kelsh SE, Girgis R, Dickinson M, McDermott JK. Everolimus Use for Intolerance or Failure of Baseline Immunosuppression in Adult Heart and Lung Transplantation. Ann Transplant. 2018 Oct 23;23:744-750. doi: 10.12659/AOT.910952.
- Background: PubMed 25580277Lopez P, Kohler S, Dimri S. Interstitial Lung Disease Associated with mTOR Inhibitors in Solid Organ Transplant Recipients: Results from a Large Phase III Clinical Trial Program of Everolimus and Review of the Literature. J Transplant. 2014;2014:305931. doi: 10.1155/2014/305931. Epub 2014 Dec 18.
- Background: PubMed 25912929Klawitter J, Nashan B, Christians U. Everolimus and sirolimus in transplantation-related but different. Expert Opin Drug Saf. 2015 Jul;14(7):1055-70. doi: 10.1517/14740338.2015.1040388. Epub 2015 Apr 26.
- Background: PubMed 32355853Chung PA, Dilling DF. Immunosuppressive strategies in lung transplantation. Ann Transl Med. 2020 Mar;8(6):409. doi: 10.21037/atm.2019.12.117.
- Background: PubMed 31379869Tissot A, Danger R, Claustre J, Magnan A, Brouard S. Early Identification of Chronic Lung Allograft Dysfunction: The Need of Biomarkers. Front Immunol. 2019 Jul 17;10:1681. doi: 10.3389/fimmu.2019.01681. eCollection 2019.
- Background: PubMed 30962148Verleden GM, Glanville AR, Lease ED, Fisher AJ, Calabrese F, Corris PA, Ensor CR, Gottlieb J, Hachem RR, Lama V, Martinu T, Neil DAH, Singer LG, Snell G, Vos R. Chronic lung allograft dysfunction: Definition, diagnostic criteria, and approaches to treatment-A consensus report from the Pulmonary Council of the ISHLT. J Heart Lung Transplant. 2019 May;38(5):493-503. doi: 10.1016/j.healun.2019.03.009. Epub 2019 Apr 3. No abstract available.
- Background: PubMed 33232061Mrad A, Chakraborty RK. Lung Transplant Rejection. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK564391/
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bronchiolitis Obliterans Syndrome (BOS), run by Fondazione IRCCS Policlinico San Matteo di Pavia at 1 site 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 0 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: finished, as of the sponsor's last update on 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TGF-beta's levels in BAL cells (time frame: from 24 hours to 72 hours of treatment). 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 NCT07234760, which also lists 7 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 18 Nov 2025.