Biomarkers in Vascular Ehlers-Danlos Syndrome (MEDIC)

Identification of Plasmatic Biomarkers in Vascular Ehlers-Danlos Syndrome

The purpose of this study is to determine whether patients with vascular Ehlers-Danlos syndrome present significant and specific changes of arterial endothelial and smooth muscular cell signalling/secretion, in comparison to matched healthy volunteers and patients with spontaneous arterial dissections.

Study Overview

• Status: Completed
• Conditions: Vascular Ehlers-Danlos Syndrome

Detailed Description

Vascular Ehlers-Danlos syndrome is a rare inherited disease which confers exceptional organ fragility in seamingly healthy young adults. The disease is caused by a mutation in the COL3A1 gene encoding type III collagen, critical to ensure physical resistance to mechanical stress of hollow organs. The disease results in increased tissular fragility, responsible of spontaneous arterial ruptures and dissections and spontaneous bowel perforations. The life-expectancy of patients with vascular Ehlers-Danlos syndrome is reduced by these recurring accidents. The exact mechanisms that trigger arterial accidents are unknown. Recent findings suggest a possible deleterious effect of inflammation and a possible dysregulation of the TGF-beta pathway. Thus, the purpose of this study is to identify further alterations in vascular endothelial and smooth muscular cell signalling/secretion, and to confirm previously suggested mechanisms of arterial accidents in vEDS patients.

• Study Type: Observational
• Enrollment (Actual): 211

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with vascular Ehlers-Danlos syndrome and patients with spontaneous dissection(s) will be recruited from the French National Referral Centre for Rare arterial diseases, Hopital Europeen Georges Pompidou, Paris, France. Healthy volunteers will be recruited by the clinical investigations center, Hopital Europeen Georges Pompidou, Paris, France (random community sample).

Description

Inclusion Criteria:

• Patients with vascular Ehlers-Danlos syndrome must have been positively tested for a pathogenic mutation within the COL3A1 gene.
• In patients with arterial dissection(s) any associated systemic arterial disease must have been ruled out, especially vascular Ehers-Danlos syndrome

Exclusion Criteria:

-All subjects must not present any chronic systemic disease, any acute disease within seven days prior to enrollment, diabetes mellitus and arterial hypertension.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Vascular-Ehlers Danlos syndrome; N=50 patients with vascular Ehlers-Danlos syndrome
Spontaneous arterial dissection(s); N=50 patients
Healthy volunteers; n=100 Healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic value of plasma biomarkers SEDv	Analysis of the diagnostic value of different levels of plasma concentrations of microRNAs	At the end of study (2 years after period of inclusion for first patient)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reference value of biomarkers	Compare patients with controls SEDv and two populations (patients with arterial accident spontaneous and healthy volunteers):microRNAs, the expression of circulating markers of tissue remodeling (plasma procollagen type I and III), the expression of a marker of inflammation (sensitivity C-reactive protein CRPus)	At the end of study (2 years after period of inclusion for first patient)

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Michael Frank, MD, Centre de Reference des Maladies Vasculaires Rares, Hopital Europeen Georges Pompidou, APHP, Paris France

Publications and helpful links

General Publications

• Morissette R, Schoenhoff F, Xu Z, Shilane DA, Griswold BF, Chen W, Yang J, Zhu J, Fert-Bober J, Sloper L, Lehman J, Commins N, Van Eyk JE, McDonnell NB. Transforming growth factor-beta and inflammation in vascular (type IV) Ehlers-Danlos syndrome. Circ Cardiovasc Genet. 2014 Feb;7(1):80-8. doi: 10.1161/CIRCGENETICS.113.000280. Epub 2014 Jan 6.

Helpful Links

• Click here for more information about this disease Vascular Ehlers-Danlos Syndrome

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: May 7, 2014
• First Submitted That Met QC Criteria: June 13, 2014
• First Posted (Estimate): June 17, 2014

Study Record Updates

• Last Update Posted (Estimate): March 17, 2016
• Last Update Submitted That Met QC Criteria: March 16, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Biomarkers; Pathophysiology; Ehlers-Danlos syndrome, vascular type
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Syndrome; Ehlers-Danlos Syndrome
• Other Study ID Numbers: P110907