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NCT Number: NCT07304856

Role of Extracellular Vesicles as Biomarkers of Pulmonary Involvement in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex

Lymphangioleiomyomatosis (LAM) is a rare lung disease, linked to Tuberous Sclerosis Complex (TSC) or occurring sporadically, and involves abnormal mTORC1 activation. LAM cells are neoplastic, and recent focus has turned to extracellular vesicles (EVs), which mediate tumor progression and may serve as biomarkers. This study, conducted at the Pulmonology Unit of ASST Santi Paolo e Carlo and the Pharmacology Laboratory of the University of Milan, will analyze the characteristics of serum EVs in patients with LAM and TSC. During scheduled outpatient visits, clinical and functional data and blood samples will be collected. Plasma will be separated, and EVs will be isolated via centrifugation. EVs will be analyzed for size, concentration, and molecular content (proteins, lipids, nucleic acids). The results obtained will be collected and correlated with the clinical and functional data.

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Key information

Conditions

Lymphangioleiomyomatosis (LAM) Extracellular Vesicles; Generation and Function Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphangioleiomyomatosis Lymphangiomyoma Lymphatic Diseases Lymphoproliferative Disorders Neoplasm, Lymphatic Tissue Neoplasms Neoplasms by Histologic Type Neoplasms, Connective and Soft Tissue Perivascular Epithelioid Cell Neoplasms

Age range

18 year–80 year

Sex eligibility

Female

Study type

Observational

Primary location

Pulmonology Unit ASST Santi Paolo e Carlo, Ospedale San Paolo

Milan, Milano, 20142, Italy

Location status: Recruiting

Location contact

Silvia Terraneo, MD, PhD

CONTACT

[email protected]

+390281843025

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Female participants aged ≥18 years Confirmed diagnosis of tuberous sclerosis complex (TSC) and/or lymphangioleiomyomatosis (definite diagnosis of TSC-LAM or S-LAM) Follow-up at the Pulmonology Unit of ASST Santi Paolo e Carlo, Milan Ability to provide written informed consent

Exclusion criteria

Diagnosis of "probable" or "possible" LAM Refusal to provide written informed consent

Treatment and study plan

Pulmonary Function Test

Diagnostic Test

Spirometry, Plethysmography, Diffusing capacity of the lungs for carbon monoxide (DLCO), and Six-minute walk test (6MWT).

Analysis of Extracellular Vesicles

Diagnostic Test

From the venous blood sample, plasma will be separated, and extracellular vesicles (EVs) will be isolated through serial centrifugation steps. The EVs will be analyzed to assess their concentration (particles/mL) and size (nanometers, nm). Additionally, omics analyses will be performed to study the molecular content of the EVs, including nucleic acids, proteins, and lipids.

Primary outcomes

  1. To compare the number and morphological characteristics of Extracellular Vesicles (EVs) in women with S-LAM, TSC-LAM, TSC without pulmonary involvement, and healthy controls

    Time frame: One year

    The concentration (particles/mL) and the size (nm) of EVs isolated from the plasma of 3 groups of patients (sporadic LAM, LAM associated to TSC, TSC without pulmonary involvement) and of 1 healthy control group will be assessed through Nanoparticle Tracking Analysis.

Secondary outcomes

  1. To evaluate the content of EVs (miRNA, lipids, proteins, metabolites) through omics analyses in women with S-LAM, TSC-LAM, TSC without pulmonary involvement, and healthy controls

    Time frame: One year

    The content of EVs isolated from the plasma of 3 groups of patients (plasma of 3 groups of patients (sporadic LAM, LAM associated to TSC, TSC without pulmonary involvement) and of 1 healthy control group will be assessed through

    -omics analyses.

  2. Effect of mTOR-inhibitor therapy on EVs count

    Time frame: One year

    The concentration (particles/mL) of extracellular vesicles (EVs) in patients with LAM treated with mTOR inhibitor therapy (sirolimus or everolimus) compared with patients not receiving mTOR inhibitor therapy will be assessed using Nanoparticle Tracking Analysis (NTA).

  3. Effect of mTOR-inhibitor therapy on EVs morphology

    Time frame: One Year

    The size (nanometers, nm) of extracellular vesicles (EVs) in patients with LAM treated with mTOR inhibitor therapy (sirolimus or everolimus) compared with patients not receiving mTOR inhibitor therapy will be assessed using Electron Microscopy (EM).

  4. Association between EVs characteristics and disease severity

    Time frame: One year

    The concentration (particles/mL) and size (nanometers, nm) of extracellular vesicles (EVs) isolated from the plasma of patients with S-LAM, TSC-LAM, and TSC without pulmonary involvement will be analyzed for their association with disease severity, as assessed by the number of systemic manifestations of TSC and the presence of pulmonary disease.

  5. Association between EVs characteristics and pulmonary disease severity

    Time frame: One year

    The concentration (particles/mL) and size (nanometers, nm) of extracellular vesicles (EVs) isolated from the plasma of patients with LAM (including both S-LAM and TSC-LAM) will be analyzed for their association with disease severity, based on the number of pulmonary complications, including pneumothoraces, chylothoraces, development of respiratory failure, and the need for lung transplantation.

  6. Association between EVs characteristics and pulmonary function

    Time frame: One year

    The concentration (particles/mL) and size (nanometers, nm) of extracellular vesicles (EVs) isolated from the plasma of patients with LAM (including both S-LAM and TSC-LAM) will be analyzed for their association with pulmonary function, as measured by spirometry and diffusion parameters (FEV1, FVC, and DLCO), with FEV1 and FVC expressed in liters and % predicted, and DLCO expressed as % predicted.

Sponsors and collaborators

Lead sponsor

University of Milan

Other

Registry information

Official study title

Prospective Observational Study of the Role of Extracellular Vesicles (EVs) as Biomarkers of Pulmonary Involvement in Patients With Sporadic Lymphangioleiomyomatosis (S-LAM) and Tuberous Sclerosis Complex-Associated LAM (TSC-LAM)

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Dec 26, 2025
Registry last updated
Dec 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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