ex Vivo Study of Liposomes Loaded With Everolimus in Chronic Lung Allograft Disfunction (ELIT)

November 14, 2025 updated by: Mirko Belliato, Fondazione IRCCS Policlinico San Matteo di Pavia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

19

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Lombardy
      • Pavia, Lombardy, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

BOS affected patients

Description

Inclusion Criteria:

- BOS/subjected to TX patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
BOS
Device: Liposomes
  1. 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
from 24 hours to 72 hours of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
cytokine's levels in BAL's cells
Time Frame: from 24 hours to 72 hours of treatment
Compare IL6, IL8, and IL10 levels in BAL cells in the four conditions.
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
Compare the levels of cytokines IL6, IL8, IL10, and TGF-beta released by PCLSs derived from explanted lungs and evaluate toxicity and cell proliferation.
from 24 hours to 72 hours of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Policlinico San Matteo di Pavia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 19, 2022

Primary Completion (Actual)

April 20, 2022

Study Completion (Actual)

July 1, 2025

Study Registration Dates

First Submitted

September 22, 2025

First Submitted That Met QC Criteria

November 14, 2025

First Posted (Actual)

November 18, 2025

Study Record Updates

Last Update Posted (Actual)

November 18, 2025

Last Update Submitted That Met QC Criteria

November 14, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ELIT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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