Mutations Affecting the COL5A GeneFLEX5 projectNCT07282717
Fibroblast Line Evaluation for COL5A eXpression and Thoracic Aortic Aneurysms: in Vitro Characterization of Cutaneous Fibroblasts in Adult Patients
An observational study of Mutations Affecting the COL5A Gene and Aneurysm Aortic, run by IRCCS Policlinico S. Donato at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mutations Affecting the COL5A Gene, Aneurysm Aortic
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 24 Jun 2026to Dec 2028
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Research hospital for rare cardiovascular diseases
Who may be able to join
- Subjects aged 18 and above
- Mutation in COL5A
- Signed informed consent
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Alessandro Pini Alessandro Giorgio Pini,MD, Medical degree contact
Italy1 site, 1 recruiting
- Recruiting
Cardiovascular Genetic Centre IRCCS Policlinico San Donato
San Donato Milanese, Italy, 20097
Nathasha Samali UDUGAMPOLAGE, (+39) 02 52774705, Nathasha.Udugampolage@grupposandonato.it
Alessandro Pini, MD
About this study
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.
Read the 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.
- Keywords
- COL5A, FIBROBLASTS, ascending and descending aortic aneurysms, thoracic aortic aneurysms
- Medical subject headings
- Aortic Aneurysm, Aortic Aneurysm, Thoracic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2025
- Study start24 Jun 2026
- Primary completionJan 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mutations Affecting the COL5A GeneStudies 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Policlinico S. Donato
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessandro Pini, IRCCS Policlinico S. Donato
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07282717
- Sponsor's protocol ID
- FLEX5 project
- Acronym
- FLEX5 project
- Status last verified
- Jul 2026
- First submitted
- 2 Dec 2025
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD sharing will be defined at the active enrolment process of the study
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.
PubMed 32990218Lu 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.
PubMed 21917992Plikus 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.
PubMed 34297930
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fibroblast Line Evaluation for COL5A eXpression and Thoracic Aortic Aneurysms: in Vitro Characterization of Cutaneous Fibroblasts in Adult Patients
- ClinicalTrials.gov ID
- NCT07282717
- Acronym / sponsor ID
- FLEX5 project / FLEX5 project
- Keywords
- COL5A, FIBROBLASTS, ascending and descending aortic aneurysms, thoracic aortic aneurysms
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- IRCCS Policlinico S. DonatoUniversity, hospital or other
- Study start
- 24 Jun 2026 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 15 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.
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.
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Research hospital for rare cardiovascular diseases
Key inclusion criteria (3 listed)
- Subjects aged 18 and above
- Mutation in COL5A
- Signed informed consent
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Fibroblasts phenotype
Time frame: 24 months
In vitro characterization and evaluation of fibroblasts phenotype in adult patients with COL5A mutations with or without aortic involvement (ascending and descending aortic aneurysms)
Differences molecular mechanisms in collagen
Time frame: 24 months
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
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 2 Jul 2026.
- Results publication: PubMed 32990218Phan 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.
- Results publication: PubMed 21917992Lu 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.
- Results publication: PubMed 34297930Plikus 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.
- Individual participant dataSharing planned: No. IPD sharing will be defined at the active enrolment process of the study
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.
Alessandro Pini Alessandro Giorgio Pini,MD, Medical degree contact
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 Mutations Affecting the COL5A Gene and Aneurysm Aortic, run by IRCCS Policlinico S. Donato 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 3 inclusion and 6 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 2 Jul 2026. 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?
Contact Alessandro Pini Alessandro Giorgio Pini,MD, Medical degree (+39 0252774705, segreteria.cardiogenetica@grupposandonato.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fibroblasts phenotype (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07282717, which also lists 3 linked publications.
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 2 Jul 2026.