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

NCT07234760 | Completed

• 1 other identifier: ELIT
• Study Type: observational
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Bronchiolitis Obliterans Syndrome (BOS)

Keywords

liposome

Outcome Measures

Primary Outcomes (1)

• 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

  from 24 hours to 72 hours of treatment

Secondary Outcomes (2)

• cytokine's levels in BAL's cells

  from 24 hours to 72 hours of treatment

• cytokines and TGF-beta's levels released by PCLSs

  from 24 hours to 72 hours of treatment

Study Arms (1)

BOS

Device: Liposomes

Interventions

Liposomes DEVICE

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

BOS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

BOS affected patients

You may qualify if:

• \- BOS/subjected to TX patients

Sponsors & Collaborators

• Fondazione IRCCS Policlinico San Matteo di Pavia: lead

Study Sites (1)

Fondazione IRCCS Policlinico San Matteo

Pavia, Lombardy, 27100, Italy

Location

Related Publications (7)

• 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.

  PMID: 30348935 BACKGROUND

• Lopez 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.

  PMID: 25580277 BACKGROUND

• Klawitter 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.

  PMID: 25912929 BACKGROUND

• Chung PA, Dilling DF. Immunosuppressive strategies in lung transplantation. Ann Transl Med. 2020 Mar;8(6):409. doi: 10.21037/atm.2019.12.117.

  PMID: 32355853 BACKGROUND

• Tissot 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.

  PMID: 31379869 BACKGROUND

• Verleden 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.

  PMID: 30962148 BACKGROUND

• Mrad A, Chakraborty RK. Lung Transplant Rejection. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK564391/

  PMID: 33232061 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

PCLS (precision cut lung slices); Lung fibroblast

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: November 18, 2025
• Study Start: March 19, 2022
• Primary Completion: April 20, 2022
• Study Completion: July 1, 2025
• Last Updated: November 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)