Lymphangioleiomyomatosis (LAM)NCT07304856
Role of Extracellular Vesicles as Biomarkers of Pulmonary Involvement in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex
An observational study of Lymphangioleiomyomatosis (LAM) and Extracellular Vesicles; Generation and Function, run by University of Milan at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Lymphangioleiomyomatosis (LAM), Extracellular Vesicles; Generation and Function
- What is being tested?
- Pulmonary Function Test and Analysis of Extracellular Vesicles
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- 16 Apr 2025to 20 Aug 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Diagnosis of "probable" or "possible" LAM Refusal to provide written informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Pulmonology Unit ASST Santi Paolo e Carlo, Ospedale San Paolo
Milan, Milano, 20142
Silvia Terraneo, MD, PhD, +390281843025, silvia.terraneo@asst-santipaolocarlo.it
About this study
Official 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)
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.
- Being tested
- Pulmonary Function Test, Analysis of Extracellular Vesicles
- Keywords
- LAM, TSC, EVs
- Medical subject headings
- Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulmonary Function TestDiagnostic test
Spirometry, Plethysmography, Diffusing capacity of the lungs for carbon monoxide (DLCO), and Six-minute walk test (6MWT).
Analysis of Extracellular VesiclesDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| S-LAM | Patients with sporadic LAM Receives: Diagnostic Test: Pulmonary Function Test; Diagnostic Test: Analysis of Extracellular Vesicles | |
| TSC-LAM | Patients with TSC-associated LAM Receives: Diagnostic Test: Pulmonary Function Test; Diagnostic Test: Analysis of Extracellular Vesicles | |
| TSC | Patients with TSC and no pulmonary involvement Receives: Diagnostic Test: Pulmonary Function Test; Diagnostic Test: Analysis of Extracellular Vesicles | |
| Control | Healthy subjects Receives: Diagnostic Test: Pulmonary Function Test; Diagnostic Test: Analysis of Extracellular Vesicles |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: One year
Effect of mTOR-inhibitor therapy on EVs count
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).
Measured: One year
Effect of mTOR-inhibitor therapy on EVs morphology
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).
Measured: One Year
Association between EVs characteristics and disease severity
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.
Measured: One year
Association between EVs characteristics and pulmonary disease severity
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.
Measured: One year
Association between EVs characteristics and pulmonary function
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2025
- Study start16 Apr 2025
- Primary completion16 Jan 2026 (estimated)
- Study completion20 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lymphangioleiomyomatosis (LAM)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michele Mondoni, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07304856
- Sponsor's protocol ID
- LAM_EVs
- Status last verified
- Sep 2025
- First submitted
- 15 Sep 2025
- Last updated
- 26 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT07304856
- Acronym / sponsor ID
- LAM_EVs
- Keywords
- LAM, TSC, EVs
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- 16 Apr 2025 (actual)
- Primary completion
- 16 Jan 2026 (estimated)
- Study completion
- 20 Aug 2026 (estimated)
- First posted
- 26 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| S-LAM | – | Diagnostic Test: Pulmonary Function Test, Diagnostic Test: Analysis of Extracellular VesiclesPatients with sporadic LAM |
| TSC-LAM | – | Diagnostic Test: Pulmonary Function Test, Diagnostic Test: Analysis of Extracellular VesiclesPatients with TSC-associated LAM |
| TSC | – | Diagnostic Test: Pulmonary Function Test, Diagnostic Test: Analysis of Extracellular VesiclesPatients with TSC and no pulmonary involvement |
| Control | – | Diagnostic Test: Pulmonary Function Test, Diagnostic Test: Analysis of Extracellular VesiclesHealthy subjects |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- Diagnosis of "probable" or "possible" LAM Refusal to provide written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pulmonary Function TestSpirometry, Plethysmography, Diffusing capacity of the lungs for carbon monoxide (DLCO), and Six-minute walk test (6MWT). | Diagnostic test | Control, S-LAM, TSC, TSC-LAM |
| Analysis of Extracellular VesiclesFrom 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. | Diagnostic test | Control, S-LAM, TSC, TSC-LAM |
Primary outcome
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.
6 secondary outcomes
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
Effect of mTOR-inhibitor therapy on EVs count
Time frame: One year
Effect of mTOR-inhibitor therapy on EVs morphology
Time frame: One Year
Association between EVs characteristics and disease severity
Time frame: One year
Association between EVs characteristics and pulmonary disease severity
Time frame: One year
Association between EVs characteristics and pulmonary function
Time frame: One year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Pulmonology Unit ASST Santi Paolo e Carlo, Ospedale San Paolo
Milan, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lymphangioleiomyomatosis (LAM) and Extracellular Vesicles; Generation and Function, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2025.