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

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ClinicalTrials.gov Identifier: NCT02202291
Recruitment Status : Completed
First Posted : July 29, 2014
Last Update Posted : June 24, 2020
Sponsor:
Information provided by (Responsible Party):
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).


Condition or disease Intervention/treatment Phase
Primary Raynaud's Phenomenon (PR) Genetic Mutations Causing PR Study of Patients and Their Relatives (With or Without Primary PR) Genetic: Demonstration of genetic mutations causing Raynaud's phenomenon Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 258 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Prospective Multicenter Study on the Identification of Genetic Abnormalities Predisposing to Vasospasm From a Privileged Model: the Primary Raynaud's Phenomenon
Actual Study Start Date : October 13, 2014
Actual Primary Completion Date : June 10, 2020
Actual Study Completion Date : June 10, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Patient with Raynaud's phenomenon Genetic: Demonstration of genetic mutations causing Raynaud's phenomenon

Such an approach allows to highlight chromosomal regions shared only by individuals within a family and thus highlight the genetic mutations causing the Raynaud phenomenon . The ultimate goal is to identify new pathways involved in vasospasm.

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.

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.

Other Names:
  • Recruitment of familial forms of Raynaud phenomenon (patients with primary
  • Raynaud phenomenon and their relatives) to perform genetic analysis of
  • exome sequencing type combined with an analysis of family bonding.




Primary Outcome Measures :
  1. To identify number of genes involved in vasospasm of primary Raynaud's phenomenon (RP) and determine the genetic cause of primary RP [ Time Frame: 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 :
  1. To determine number of phenotypes associated to genotype of primary Raynaud's phenomenon [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02202291


Locations
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France
CHU Angers - Service d'Explorations vasculaires
Angers, France, 49033 Angers Cedex 01
CHRU HOPITAL CAVALE BLANCHE - Service de Médecine vasculaire
Brest, France, 29609 Brest Cedex 2
CHD La Roche sur Yon - Service Angéiologie
La Roche sur Yon, France, 85925 La Roche/Yon Cedex 9
CHU de NANTES - Service de Médecine Interne
Nantes, France, 44000
C.H.R. HOPITAL SUD - Service de Médecine interne
Rennes, France, 35203 Rennes Cedex 2
Ch Saint Nazaire
Saint Nazaire, France, 44600
Sponsors and Collaborators
Nantes University Hospital
Investigators
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Study Director: Marc-Antoine Pistorius, Prof University Hospital of Nantes
Principal Investigator: Marc-Antoine Pistorius, Prof University Hospital of Nantes
Principal Investigator: Luc Bressollette, Prof University Hospital of Brest
Principal Investigator: Patrick Jégo, Prof University Hospital of Rennes
Principal Investigator: Samir Henni, Dr University Hospital of Angers
Principal Investigator: Jean-Manuel Kubina, Dr Hospital of La Roche/Yon
Principal Investigator: Pierre Plissonneau Duquene, Dr Hospital of St Nazaire
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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02202291    
Other Study ID Numbers: RC14_0086
2014-A00470-47 ( Other Identifier: ANSM )
First Posted: July 29, 2014    Key Record Dates
Last Update Posted: June 24, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Nantes University Hospital:
Raynaud's phenomenon, Vasospasm, Genetics
Additional relevant MeSH terms:
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Raynaud Disease
Peripheral Vascular Diseases
Vascular Diseases
Cardiovascular Diseases