Transcriptomic Study of Adult Population With Marfan Syndrome

Marfan Syndrome Clinical Trial

— MaRfaNomicA  

Official title:

Transcriptomic Study of Adult Population With Marfan Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05700175
• Other study ID #: MaRfaNomicA
• Status: Recruiting
• Start date: November 2, 2021
• Est. completion date: December 2025

Study information

• Verified date: January 2023
• Source: IRCCS Policlinico S. Donato
• Contact: Fabio Martelli, Dr
• Phone: +39 02 2643
• Email: fabio.martelli[@]grupposandonato.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

The investigators will collect peripheral blood and aortic aneurysm tissues specimens from consenting subjects. For all three groups of MFS patients, total RNA will be isolated from peripheral whole blood, plasma and peripheral blood mononuclear cell (PBMC) and processed for transcriptomic analyses by RNAseq. Plasma will be used to determine cytokine and chemokine levels, using a luminex panel designed for inflammation biomarkers (serum proteomics). For all patients undergoing surgery, tissue specimens will be used for transcriptomic and epigenetic analysis, histological sections and serum proteomics.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Marfan Syndrome
• Syndrome

Intervention

Diagnostic Test:
• Transcriptomic, epigenetic and proteomic analysis
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.

Locations

Country	Name	City	State
Italy	Irccs Policlinico San Donato	San Donato Milanese	Milan

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Donato

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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