Prospective Multicenter Study on the Identification of Genetic Abnormalities Predisposing to Vasospasm From a Privileged Model: the Primary Raynaud's Phenomenon

Not Applicable

Completed

• Conditions: Genetic Mutations Causing PR; Primary Raynaud's Phenomenon (PR); Study of Patients and Their Relatives (With or Without Primary PR)
• Interventions: Genetic: Demonstration of genetic mutations causing Raynaud's phenomenon

• Registration Number: NCT02202291
• Lead Sponsor: Nantes University Hospital

Brief Summary

Vasospasm is a transient contraction causing a decrease in caliber of a vessel and thus a decrease in vascularization in a vascular territory leading to suffering of tissue in the sector concerned. Vasospasm-related diseases have different clinical presentations such as migraine, spastic angina, hypertension related to vasospasm or primary Raynaud's phenomenon (RP). These diseases have few therapeutic methods due to poorly understood pathophysiology. For migraine and angina, the vascular exploration is problematic unlike for primary Raynaud's phenomenon (RP).

Primary Raynaud's phenomenon (RP) is a common peripheral vascular disease to cold with an estimated prevalence between 5-9 % of the general population. It is the expression of an extreme vasospasm microcirculation of the extremities linked to hypersensitivity to cold and that is clinically expressed by the occurrence of syncope stages where the fingers are anesthetized and white, followed by a stage with hyperemic restaining .

The objective of our study is to identify new metabolic pathways involved in vasospasm in order to consider new specific treatments, currently lacking.

The identification of these pathways will be made by the detection of genetic abnormalities causing vasospasm in Raynaud's phenomenon. This disease is a perfectly appropriate model to study vasospasm by its high frequency in the population, its hereditary nature and simple diagnosis. The powerful current genetic strategies will be applied to this model (exome sequencing combined to family connection analysis).

Detailed Description

Patients with primary Raynaud phenomenon will be identified during a consultation of vascular medicine and internal medicine in one of the centers participating to the study. Those patients with a primary PR will be considered as Index cases.

In all participating centers, there will be a recruitment of index cases without family screening to form a series of cases that will validate the results obtained in family forms.

The investigators will conduct genealogical trees of index cases to identify families, whose number of healthy individuals and those with relevant PR makes sense for a family genetic study, i.e. a genetically informative family.

In all centers, relatives of included Index cases, agreeing to participate in this research, will be enrolled and followed.

Nantes University Hospital is the only center to perform a cold test (for reasons of availability of the technique) but this test will be reserved for patients whose diagnosis of primary Raynaud's phenomenon would be doubtful. Exposed identified relatives, agreeing to participate in this research, will all be included and followed in their enrollment center.

Study Timeline

• Study First Submitted: 2014-07-15
• Study First Submitted QC: 2014-07-24
• Study First Posted: 2014-07-29
• Study Start: 2014-10-13
• Status Verified: 2020-06
• Primary Completion: 2020-06-10
• Study Completion: 2020-06-10
• Last Update Submitted: 2020-06-22
• Last Update Posted: 2020-06-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 258

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Patient with Raynaud's phenomenon	Demonstration of genetic mutations causing Raynaud's phenomenon	-

Primary Outcome Measures

Name	Time	Method
To identify number of genes involved in vasospasm of primary Raynaud's phenomenon (RP) and determine the genetic cause of primary RP	36 months	Patients with primary Raynaud's phenomenon and their relatives will be recruited to establish familial forms of Raynaud's phenomenon. This will allow perform genetic analysis using new approaches to genetic broadband (exome sequencing analysis + linkage analysis). This approach will allow specify which chromosomal regions are shared only by affected individuals, and identify new candidate genes

Secondary Outcome Measures

Name	Time	Method
To determine number of phenotypes associated to genotype of primary Raynaud's phenomenon	36 months	Based on the identified genes in different families, a descriptive analysis will allow associate them with different RP phenotypes (isolated RP or RP associated with migraines, angina or hypertension) and risk factors.

Trial Locations

Locations (6)

Ch Saint Nazaire; 🇫🇷 Saint Nazaire, France

CHRU HOPITAL CAVALE BLANCHE - Service de Médecine vasculaire; 🇫🇷 Brest, France

CHU Angers - Service d'Explorations vasculaires; 🇫🇷 Angers, France

CHU de NANTES - Service de Médecine Interne; 🇫🇷 Nantes, France

CHD La Roche sur Yon - Service Angéiologie; 🇫🇷 La Roche sur Yon, France

C.H.R. HOPITAL SUD - Service de Médecine interne; 🇫🇷 Rennes, France