Transcriptomic Study of Adult Population With Marfan Syndrome

NCT05700175 | Recruiting DMC

• 1 other identifier: MaRfaNomicA
• Study Type: observational
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

This project is designed to discover circulating biomarkers for aortic aneurysms in adults affected by Marfan Syndrome (MFS). The first aim is to identify circulating transcripts, protein-coding (mRNA) and not (ncRNAs), which show differential expression between three groups of adult patients affected by MFS, based on: presence or absence of thoracic aortic aneurysms (TAA) and indication of TAA-surgery. This obtained TAA\_MFS\_signature will then be correlated to fundamental biological parameters, like cytokines and chemokines relevant during inflammation and transcriptomic as well as epigenetics changes in aortic aneurysm tissue. Furthermore, the association of TAA\_MFS\_signature to genetic, clinical and instrumental parameters at present used for diagnosis and treatment, will be evaluated.

Conditions

Marfan Syndrome; Marfan's Syndrome With Cardiovascular Manifestations

Keywords

Thoracic aortic aneurysm

Outcome Measures

Primary Outcomes (1)

• Transcriptomic Signature in adult patients suffering of affected by Marfan syndrome

  Identification of differences in transcript-expression between Marfan patients with or without thoracic aortic aneurysms (TAA) and with indication of TAA-surgery.

  year 1-5

Interventions

Transcriptomic, epigenetic and proteomic analysis DIAGNOSTIC_TEST

Next-generation sequencing will be used to identify differences in expression of circulating transcripts (protein-coding and not) in patients affected by Marfan Syndrome (MFS), subdivided based on the presence or absence of thoracic aortic aneurysms (TAA) and indication of TAA-surgery (TAA\_MFS\_signature). The obtained TAA\_MFS\_signature will be correlated to fundamental biological parameters by analysing: Blood-levels of cytokines and chemokines relevant for inflammation. Transcriptomic and epigenetic (Cytosine methylation) changes in aortic aneurysms tissue by Next-generation sequencing. Progression of biomarkers in surgical-patients before and at 6 and 12 months after surgery.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients treated at the IRCCS Policlinico San Donato.

You may qualify if:

• General criteria:
• Clinically and genetically determined Marfan syndrome (according to the revised Ghent-criteria 2010)
• Signed informed consent
• Patient receiving regular pharmacological prophylaxis or newly diagnosed patients
• Population without thoracic aortic aneurysms (TAA) Patients with clinically and genetically determined Marfan syndrome, presenting thoracic aortic diameters within established normal limits (mm and base Z-score).
• Population with TAA "stable dimensions" Patients with clinically and genetically determined Marfan syndrome, presenting stable values for dimension / Z-score of the aortic root during the 12 months preceding the enrolment.
• Population with TAA with surgery indication:
• Patients with clinically and genetically determined Marfan syndrome, presenting indication for surgical correctional according to the relevant International guidelines
• Trend of uncontrolled increase of aortic diameter compared to previous measurements
• Aortic ectasia associated to a clinically significant valve dysfunction
• Evaluation of cut-off for surgical intervention dependant also on familial dissection

You may not qualify if:

• Patients with chronic or acute inflammation states, like: chronic liver disease, chronic renal insufficiency (creatinine \> 1.5 mg/dl) and diseases affecting the thyroid apparatus.
• Pregnancy

Sponsors & Collaborators

• IRCCS Policlinico S. Donato: lead

Study Sites (1)

Irccs Policlinico San Donato

San Donato Milanese, Milan, 20097, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

peripheral blood aortic aneurysmal tissue

MeSH Terms

Conditions

Marfan Syndrome; Aortic Aneurysm, Thoracic

Interventions

Epigenesis, Genetic

Condition Hierarchy (Ancestors)

Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Aortic Aneurysm; Aneurysm; Vascular Diseases; Aortic Diseases

Intervention Hierarchy (Ancestors)

Gene Expression Regulation; Genetic Phenomena

Study Officials

• Fabio Martelli, Dr

  IRCCS Policlinico S. Donato

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabio Martelli, Dr

CONTACT

+39 02 2643; fabio.martelli@grupposandonato.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr, PhD, Molecular Cardiology Laboratory Director

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: January 26, 2023
• Study Start: November 2, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 13, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)