Ignite Creation Date:
2026-03-26 @ 3:17 PM
Ignite Modification Date:
2026-03-29 @ 11:25 PM
Study NCT ID:
NCT07304856
Status:
RECRUITING
Last Update Posted:
2025-12-26
First Post:
2025-09-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Role of Extracellular Vesicles as Biomarkers of Pulmonary Involvement in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018192', 'term': 'Lymphangioleiomyomatosis'}], 'ancestors': [{'id': 'D008203', 'term': 'Lymphangiomyoma'}, {'id': 'D018190', 'term': 'Neoplasm, Lymphatic Tissue'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D054973', 'term': 'Perivascular Epithelioid Cell Neoplasms'}, {'id': 'D018204', 'term': 'Neoplasms, Connective and Soft Tissue'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D012129', 'term': 'Respiratory Function Tests'}], 'ancestors': [{'id': 'D003948', 'term': 'Diagnostic Techniques, Respiratory System'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'CROSS_SECTIONAL', 'observationalModel': 'OTHER'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 80}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-04-16', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2026-08-20', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-12', 'studyFirstSubmitDate': '2025-09-15', 'studyFirstSubmitQcDate': '2025-12-12', 'lastUpdatePostDateStruct': {'date': '2025-12-26', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-12-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-01-16', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'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', 'timeFrame': 'One year', 'description': '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.'}], 'secondaryOutcomes': [{'measure': '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', 'timeFrame': 'One year', 'description': '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\n\n-omics analyses.'}, {'measure': 'Effect of mTOR-inhibitor therapy on EVs count', 'timeFrame': 'One year', 'description': '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).'}, {'measure': 'Effect of mTOR-inhibitor therapy on EVs morphology', 'timeFrame': 'One Year', 'description': '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).'}, {'measure': 'Association between EVs characteristics and disease severity', 'timeFrame': 'One year', 'description': '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.'}, {'measure': 'Association between EVs characteristics and pulmonary disease severity', 'timeFrame': 'One year', 'description': '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.'}, {'measure': 'Association between EVs characteristics and pulmonary function', 'timeFrame': 'One year', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['LAM, TSC, EVs'], 'conditions': ['Lymphangioleiomyomatosis (LAM)', 'Extracellular Vesicles; Generation and Function']}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': '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.', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\nFemale 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\n\nExclusion Criteria:\n\nDiagnosis of "probable" or "possible" LAM Refusal to provide written informed consent'}, 'identificationModule': {'nctId': 'NCT07304856', 'briefTitle': 'Role of Extracellular Vesicles as Biomarkers of Pulmonary Involvement in Patients With Lymphangioleiomyomatosis and Tuberous Sclerosis Complex', 'organization': {'class': 'OTHER', 'fullName': 'University of Milan'}, 'officialTitle': '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)', 'orgStudyIdInfo': {'id': 'LAM_EVs'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'S-LAM', 'description': 'Patients with sporadic LAM', 'interventionNames': ['Diagnostic Test: Pulmonary Function Test', 'Diagnostic Test: Analysis of Extracellular Vesicles']}, {'label': 'TSC-LAM', 'description': 'Patients with TSC-associated LAM', 'interventionNames': ['Diagnostic Test: Pulmonary Function Test', 'Diagnostic Test: Analysis of Extracellular Vesicles']}, {'label': 'TSC', 'description': 'Patients with TSC and no pulmonary involvement', 'interventionNames': ['Diagnostic Test: Pulmonary Function Test', 'Diagnostic Test: Analysis of Extracellular Vesicles']}, {'label': 'Control', 'description': 'Healthy subjects', 'interventionNames': ['Diagnostic Test: Pulmonary Function Test', 'Diagnostic Test: Analysis of Extracellular Vesicles']}], 'interventions': [{'name': 'Pulmonary Function Test', 'type': 'DIAGNOSTIC_TEST', 'description': 'Spirometry, Plethysmography, Diffusing capacity of the lungs for carbon monoxide (DLCO), and Six-minute walk test (6MWT).', 'armGroupLabels': ['Control', 'S-LAM', 'TSC', 'TSC-LAM']}, {'name': 'Analysis of Extracellular Vesicles', 'type': 'DIAGNOSTIC_TEST', 'description': '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.', 'armGroupLabels': ['Control', 'S-LAM', 'TSC', 'TSC-LAM']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20142', 'city': 'Milan', 'state': 'Milano', 'status': 'RECRUITING', 'country': 'Italy', 'contacts': [{'name': 'Silvia Terraneo, MD, PhD', 'role': 'CONTACT', 'email': 'silvia.terraneo@asst-santipaolocarlo.it', 'phone': '+390281843025'}], 'facility': 'Pulmonology Unit ASST Santi Paolo e Carlo, Ospedale San Paolo', 'geoPoint': {'lat': 42.78235, 'lon': 12.59836}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Milan', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD, associated professor of respiratory medicine', 'investigatorFullName': 'Michele Mondoni', 'investigatorAffiliation': 'University of Milan'}}}}