Genes Modulating the Severity of Aortic Aneurysms (MSF1-TGFBR2)

NCT05146375 | Active Not Recruiting

• 1 other identifier: 2021-02
• Study Type: observational
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This project concerns a population at risk of sudden death by dissection of the thoracic aorta. Its interest is to make it possible to recognize the genes that protect or worsen the evolution of aneurysms, to better understand the mechanisms involved, to detect and treat aneurysms of the thoracic aorta, wich is a pathology that is completely silent clinically until life-threatening complications. The variability in the severity of the disease within the same family is related to modifier genes. The objective is to find the modifying factors that account for the variability in the severity of the progression of aneurysms of the thoracic aorta.

Conditions

Thoracic Aortic Aneurysm

Keywords

Vascular Diseases, Aneurysm; TGFBR2 mutation

Outcome Measures

Primary Outcomes (1)

• Clinical phenotype

  The criterion of severity of aortic disorder is based on the maximal aortic diameter measurement (in millimeter, measured at the level of the sinuses of Valsalva) and on age-adjusted aortic dilation.

  day 1

Secondary Outcomes (3)

• TGFBR2 and other gene mutations involved in aneurysms

  All samples will be analysed at the same time, at the end of the recruitment.

• Genotype analysis

  All samples will be analysed at the same time, at the end of the recruitment.

• Transcriptome analysis

  All samples will be analysed at the same time, at the end of the recruitment.

Study Arms (1)

MSF1

Each member of the MSF1 family who consents to participate to the study will be included.

Biological: TGFBR2

Interventions

TGFBR2 BIOLOGICAL

TGFBR2 mutation correlation with severity of the aortic disease. Blood sampling. Serum will be analysed by DNA sequencing to detect specific mutations involved in aneurysms. Cutaneous biopsy. Fibroblast culture will be done to assess the transcriptome analysis.

MSF1

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

53 members of the MFS1 family are currently identified and have a medical follow-up in the national referral center for Marfan syndrome of the hospital Bichat-Claude Bernard, Paris.

You may qualify if:

• Member of MSF1 family. The MFS1 family is a family in which the aortic pathology is due to a mutation in the TGFBR2 gene. All patients with this family carry the same TGFBR2 mutation (heterozygous)

You may not qualify if:

• Refusal or linguistic or psychological inability to sign informed consent

Sponsors & Collaborators

• French Cardiology Society: lead
• Fédération Française de Cardiologie: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Hopital Bichat-Claude Bernard

Paris, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood sample (serum)

MeSH Terms

Conditions

Aortic Aneurysm, Thoracic; Vascular Diseases; Aneurysm

Interventions

Receptor, Transforming Growth Factor-beta Type II

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Cardiovascular Diseases; Aortic Diseases

Intervention Hierarchy (Ancestors)

Protein Serine-Threonine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Transforming Growth Factor beta; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Receptors, Growth Factor; Receptors, Peptide

Study Officials

• Guillaume JONDEAU, MD

  Hopital Bichat-Claude Bernard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2021
• First Posted: December 6, 2021
• Study Start: November 24, 2022
• Primary Completion: September 28, 2023
• Study Completion: November 30, 2025
• Last Updated: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)