Clinical trial NCT02202291: Prospective Multicenter Study on the Identification of Genetic Abnormalities Predisposing to Vasospasm From a Privileged Model: the Primary Raynaud's Phenomenon
Official title: Prospective Multicenter Study on the Identification of Genetic Abnormalities Predisposing to Vasospasm From a Privileged Model: the Primary Raynaud's Phenomenon
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Primary Raynaud's Phenomenon (PR)
Genetic Mutations Causing PR
Study of Patients and Their Relatives (With or Without Primary PR)
Keywords: Raynaud's phenomenon, Vasospasm, Genetics
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2014-07-29
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion criteria:

* Major Subject (age ≥ 18 years)
* Index case with all the diagnostic criteria for primary Raynaud phenomenon, according to current recommendations OR Related index case (relatives' patients) with or without a primary Raynaud phenomenon.
* Written consent to participate in the study
* Written consent to participate in the collection of biological samples

Exclusion criteria:

* Subjects who have expressed their inability or refusal to sign an informed consent,
* Index case with a secondary Raynaud phenomenon (suspected by clinical examination and confirmed by capillaroscopy and laboratory tests: antinuclear antibody, abnormalities of capillaroscopy mégacapillaire dystrophy or other major deviation).

(Criterion not applicable to related parties, i.e. family members of Index cases)

- Pregnant Woman.

Primary outcomes:
measure: To identify number of genes involved in vasospasm of primary Raynaud's phenomenon (RP) and determine the genetic cause of primary RP
timeFrame: 36 months
Secondary outcomes:
measure: To determine number of phenotypes associated to genotype of primary Raynaud's phenomenon
timeFrame: 36 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers - Service d'Explorations vasculaires
city: Brest
country: France
facility: CHRU HOPITAL CAVALE BLANCHE - Service de Médecine vasculaire
city: La Roche sur Yon
country: France
facility: CHD La Roche sur Yon - Service Angéiologie
city: Nantes
country: France
facility: CHU de NANTES - Service de Médecine Interne
city: Rennes
country: France
facility: C.H.R. HOPITAL SUD - Service de Médecine interne
city: Saint Nazaire
country: France
facility: Ch Saint Nazaire
Study officials:
affiliation: University Hospital of Nantes
name: Marc-Antoine Pistorius, Prof
role: STUDY_DIRECTOR
affiliation: University Hospital of Nantes
name: Marc-Antoine Pistorius, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Brest
name: Luc Bressollette, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Rennes
name: Patrick Jégo, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Angers
name: Samir Henni, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital of La Roche/Yon
name: Jean-Manuel Kubina, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital of St Nazaire
name: Pierre Plissonneau Duquene, Dr
role: PRINCIPAL_INVESTIGATOR
References: