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

NCT07304856 | Recruiting

• 1 other identifier: LAM_EVs
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphangioleiomyomatosis (LAM); Extracellular Vesicles; Generation and Function

Keywords

LAM, TSC, EVs

Outcome Measures

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

  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.

  One year

Secondary Outcomes (6)

• 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

  One year

• Effect of mTOR-inhibitor therapy on EVs count

  One year

• Effect of mTOR-inhibitor therapy on EVs morphology

  One Year

• Association between EVs characteristics and disease severity

  One year

• Association between EVs characteristics and pulmonary disease severity

  One year

Study Arms (4)

S-LAM

Patients with sporadic LAM

Diagnostic Test: Pulmonary Function Test; Diagnostic Test: Analysis of Extracellular Vesicles

TSC-LAM

Patients with TSC-associated LAM

Diagnostic Test: Pulmonary Function Test; Diagnostic Test: Analysis of Extracellular Vesicles

TSC

Patients with TSC and no pulmonary involvement

Diagnostic Test: Pulmonary Function Test; Diagnostic Test: Analysis of Extracellular Vesicles

Control

Healthy subjects

Diagnostic Test: Pulmonary Function Test; Diagnostic Test: Analysis of Extracellular Vesicles

Interventions

Pulmonary Function Test DIAGNOSTIC_TEST

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

Control; S-LAM; TSC; TSC-LAM

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.

Control; S-LAM; TSC; TSC-LAM

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Female participants aged ≥18 years with a confirmed diagnosis of tuberous sclerosis complex (TSC) and/or lymphangioleiomyomatosis (LAM), followed at the Pulmonology Unit of ASST Santi Paolo e Carlo, Milan, and able to provide written informed consent.

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Milan: lead

Study Sites (1)

Pulmonology Unit ASST Santi Paolo e Carlo, Ospedale San Paolo

Milan, Milano, 20142, Italy

RECRUITING

MeSH Terms

Conditions

Lymphangioleiomyomatosis

Interventions

Respiratory Function Tests

Condition Hierarchy (Ancestors)

Lymphangiomyoma; Neoplasm, Lymphatic Tissue; Neoplasms by Histologic Type; Neoplasms; Perivascular Epithelioid Cell Neoplasms; Neoplasms, Connective and Soft Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, associated professor of respiratory medicine

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: December 26, 2025
• Study Start: April 16, 2025
• Primary Completion: January 16, 2026
• Study Completion (Estimated): August 20, 2026
• Last Updated: December 26, 2025

Record last verified: 2025-09

Locations

IT (1)