Clinical trial NCT06786754: Fibroblasts and Thoracic Aortic Aneurysms: in Vitro Characterization in With Marfan Syndrome and Genetic Aortic Diseases
Official title: FIBROBLASTS AND THORACIC AORTIC ANEURYSMS: IN VITRO CHARACTERIZATION IN PATIENTS WITH MARFAN SYNDROME AND GENETIC AORTIC DISEASES
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Rare Diseases
Thoracic Aortic Aneurysm (TAA)
Marfan Syndrome
Keywords: Fibroblasts
Collagen turnover
thoracic aortic aneuryms
Lead sponsor: IRCCS Policlinico S. Donato
Sponsor class: OTHER
Collaborators: name: University of Milan
First posted: 2025-01-22
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: resaerch hospital for rare cardiovascular diseases

Brief summary: The aim of the present study is to characterise the phenotype of fibroblasts and to classify different mechanisms involved in the onset and progression of TAAD in syndromic and non-syndromic subjects in order to evaluate potential markers related to TAAD.

Detailed description: The aim of the study is to analyse cutaneous fibroblast properties in patients with thoracic aortic aneurysms (both syndromic and non-syndromic) to identify differences in molecular mechanisms in collagen turnover pathways compared to healthy controls in the general population.

Eligibility criteria: Inclusion Criteria (general for the study):

signed informed consent; subjects aged 18 years and above.

Inclusion Criteria (Case):

subjects with Marfan syndrome and thoracic aortic aneurysms (in clinical follow-up or with cardiac surgery program); subjects with non-syndromic thoracic aortic aneurysms (in clinical follow-up or with cardiac surgery program);

Inclusion Criteria (healthy controls):

absence of any aortic/thoracic disease;

Exclusion Criteria (all groups):

* Presence of any confounding cardiovascular risk factor (hypertension, dyslipidaemia, diabetes, smoking habits) or previous cardiovascular disease
* Corticosteroid or Steroids or Fluorochinolones treatment within six months before enrollment Subjects on chronic immunosuppressive therapies such as oral steroids, but also on chronic topical steroids in the area of investigation;
* A history of keloid formation (data found in anamnesis and medical records);
* Anaesthetic drug allergy (data found in anamnesis and medical records).

Primary outcomes:
measure: Fibroblasts phenotype: cell morphology and migration
timeFrame: 12 months
measure: Fibroblasts phenotype: cell morphology and migration
timeFrame: 12 months
Secondary outcomes:
measure: Expression of genes and proteins involved in collagen turnover and extracellular matrix remodeling pathways
timeFrame: 16 months
measure: Expression of genes and proteins involved in collagen turnover and extracellular matrix remodeling pathways
timeFrame: 16 months
measure: Levels of metalloproteinases involved in ECM degradation
timeFrame: 24 months
Other outcomes:
Locations:
city: San Donato Milanese
country: Italy
facility: Cardiovascular Genetic Centre IRCCS Policlinico San Donato
state: Milan
Study officials:
References:
citation: Ignotz RA, Massague J. Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix. J Biol Chem. 1986 Mar 25;261(9):4337-45.
citation: Lu P, Takai K, Weaver VM, Werb Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol. 2011 Dec 1;3(12):a005058. doi: 10.1101/cshperspect.a005058.
citation: Plikus MV, Wang X, Sinha S, Forte E, Thompson SM, Herzog EL, Driskell RR, Rosenthal N, Biernaskie J, Horsley V. Fibroblasts: Origins, definitions, and functions in health and disease. Cell. 2021 Jul 22;184(15):3852-3872. doi: 10.1016/j.cell.2021.06.024.