Fibroblast Line Evaluation for COL5A eXpression and Thoracic Aortic Aneurysms: in Vitro Characterization of Cutaneous Fibroblasts in Adult Patients (FLEX5 project)

This study examines adults with COL5A gene mutations to understand why some develop aortic aneurysms while others do not. Participants provide a small skin biopsy, and researchers analyze fibroblasts to evaluate collagen production, extracellular matrix organization, and connective-tissue signaling pathways. The goal is to identify biological differences that may explain variable vascular risk and support future personalized monitoring and treatment strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Aneurysm Aortic; Mutations Affecting the COL5A Gene

Detailed Description

Individuals with mutations in the collagent type V, alpha (COL5A) gene show variable clinical outcomes. While some develop aortic aneurysms, others with the same mutation remain free of cardiovascular complications. The mechanisms driving this variability are not fully understood.

This study aims to investigate biological differences at the cellular level by analyzing fibroblasts derived from a small skin biopsy. Fibroblasts play a key role in the production and organization of type V collagen and the extracellular matrix.

Researchers will:

Grow fibroblasts from participants' skin samples.

Assess cell growth, migration, and extracellular matrix formation.

Measure the quantity and type of collagen produced.

Evaluate molecules involved in collagen breakdown and repair.

The study compares individuals with COL5A mutations who have documented aortic aneurysms to those with the same mutation but no vascular involvement. Analyses will also consider differences among family members who share the same genetic variant.

By characterizing fibroblast behavior, the study seeks to clarify why some individuals develop aortic disease while others remain unaffected. Findings may help identify cellular features associated with increased or reduced vascular risk and guide future strategies for monitoring, prevention, and personalized care in patients with COL5A mutations.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Alessandro Pini Alessandro Giorgio Pini,MD, Medical degree; Phone Number: +39 0252774705; Email: segreteria.cardiogenetica@grupposandonato.it
• Study Contact Backup: Name: Nathasha Samali Udugmpolage; Phone Number: +39 0252774705; Email: Nathasha.Udugampolage@grupposandonato.it

Study Locations

• Italy
  • Italy
    • San Donato Milanese, Italy, Italy, 20097
      • Cardiovascular Genetic Centre IRCCS Policlinico San Donato
      • Contact: Nathasha Samali UDUGAMPOLAGE; Phone Number: (+39) 02 52774705; Email: Nathasha.Udugampolage@grupposandonato.it
      • Principal Investigator: Alessandro Pini, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Research hospital for rare cardiovascular diseases

Description

Inclusion Criteria:

• Subjects aged 18 and above
• Mutation in COL5A
• Signed informed consent

Exclusion Criteria:

• 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
• Subject on anticoagulant therapy
• History of coagulation factor defects/alterations (data found in anamnesis and medical records)
• A history of keloid formation (data found in anamnesis and medical records)
• Anesthetic drug allergy (data found in anamnesis and medical records)

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Adult patients with COL5A with TAAD; Adult patients (aged over 50 years) with COL5A mutation and aortic manifestations
Adult patients with COL5A mutation without TAAD; Adult patients (aged over 50 years) with COL5A mutation in the absence of aortic manifestations
Young patients with COL5A mutation and TAAD; Young patients (aged 18-50 years) with COL5A mutation and aortic manifestations
Young patients with COL5A mutation without TAAD; Young patients (aged 18-50 years) with COL5A mutation in the absence of aortic manifestations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibroblasts phenotype	In vitro characterization and evaluation of fibroblasts phenotype in adult patients with COL5A mutations with or without aortic involvement (ascending and descending aortic aneurysms)	24 months
Differences molecular mechanisms in collagen	Identify differences in molecular mechanisms involved in collagen and ECM turnover pathways between family members according to the vascular manifestation and the genetic mutation in COL5A gene	24 months

Collaborators and Investigators

• Sponsor: IRCCS Policlinico S. Donato

Publications and helpful links

General Publications

• Phan QM, Fine GM, Salz L, Herrera GG, Wildman B, Driskell IM, Driskell RR. Lef1 expression in fibroblasts maintains developmental potential in adult skin to regenerate wounds. Elife. 2020 Sep 29;9:e60066. doi: 10.7554/eLife.60066.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): January 13, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): February 2, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: thoracic aortic aneurysms; COL5A; FIBROBLASTS; ascending and descending aortic aneurysms
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Thoracic
• Other Study ID Numbers: FLEX5 project

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD sharing will be defined at the active enrolment process of the study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No