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

NCT ID: NCT07304856

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-04-16

Study Completion Date

2026-08-20

Brief Summary

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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.

Detailed Description

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Conditions

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Lymphangioleiomyomatosis (LAM) Extracellular Vesicles; Generation and Function

Keywords

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LAM, TSC, EVs

Study Design

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Observational Model Type

OTHER

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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S-LAM

Patients with sporadic LAM

Pulmonary Function Test

Intervention Type DIAGNOSTIC_TEST

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

Analysis of Extracellular Vesicles

Intervention Type 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.

TSC-LAM

Patients with TSC-associated LAM

Pulmonary Function Test

Intervention Type DIAGNOSTIC_TEST

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

Analysis of Extracellular Vesicles

Intervention Type 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.

TSC

Patients with TSC and no pulmonary involvement

Pulmonary Function Test

Intervention Type DIAGNOSTIC_TEST

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

Analysis of Extracellular Vesicles

Intervention Type 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

Healthy subjects

Pulmonary Function Test

Intervention Type DIAGNOSTIC_TEST

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

Analysis of Extracellular Vesicles

Intervention Type 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.

Interventions

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Pulmonary Function Test

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

Intervention Type DIAGNOSTIC_TEST

Analysis of Extracellular Vesicles

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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Milan

OTHER

Sponsor Role lead

Responsible Party

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Michele Mondoni

MD, associated professor of respiratory medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Pulmonology Unit ASST Santi Paolo e Carlo, Ospedale San Paolo

Milan, Milano, Italy

Site Status RECRUITING

Countries

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Italy

Facility Contacts

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Silvia Terraneo, MD, PhD

Role: primary

Other Identifiers

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LAM_EVs

Identifier Type: -

Identifier Source: org_study_id