<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02202291</url>
  </required_header>
  <id_info>
    <org_study_id>RC14_0086</org_study_id>
    <secondary_id>2014-A00470-47</secondary_id>
    <nct_id>NCT02202291</nct_id>
  </id_info>
  <brief_title>Prospective Multicenter Study on the Identification of Genetic Abnormalities Predisposing to Vasospasm From a Privileged Model: the Primary Raynaud's Phenomenon</brief_title>
  <acronym>RAY-GENE</acronym>
  <official_title>Prospective Multicenter Study on the Identification of Genetic Abnormalities Predisposing to Vasospasm From a Privileged Model: the Primary Raynaud's Phenomenon</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nantes University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Vasospasm is a transient contraction causing a decrease in caliber of a vessel and thus a&#xD;
      decrease in vascularization in a vascular territory leading to suffering of tissue in the&#xD;
      sector concerned. Vasospasm-related diseases have different clinical presentations such as&#xD;
      migraine, spastic angina, hypertension related to vasospasm or primary Raynaud's phenomenon&#xD;
      (RP). These diseases have few therapeutic methods due to poorly understood pathophysiology.&#xD;
      For migraine and angina, the vascular exploration is problematic unlike for primary Raynaud's&#xD;
      phenomenon (RP).&#xD;
&#xD;
      Primary Raynaud's phenomenon (RP) is a common peripheral vascular disease to cold with an&#xD;
      estimated prevalence between 5-9 % of the general population. It is the expression of an&#xD;
      extreme vasospasm microcirculation of the extremities linked to hypersensitivity to cold and&#xD;
      that is clinically expressed by the occurrence of syncope stages where the fingers are&#xD;
      anesthetized and white, followed by a stage with hyperemic restaining .&#xD;
&#xD;
      The objective of our study is to identify new metabolic pathways involved in vasospasm in&#xD;
      order to consider new specific treatments, currently lacking.&#xD;
&#xD;
      The identification of these pathways will be made by the detection of genetic abnormalities&#xD;
      causing vasospasm in Raynaud's phenomenon. This disease is a perfectly appropriate model to&#xD;
      study vasospasm by its high frequency in the population, its hereditary nature and simple&#xD;
      diagnosis. The powerful current genetic strategies will be applied to this model (exome&#xD;
      sequencing combined to family connection analysis).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with primary Raynaud phenomenon will be identified during a consultation of vascular&#xD;
      medicine and internal medicine in one of the centers participating to the study. Those&#xD;
      patients with a primary PR will be considered as Index cases.&#xD;
&#xD;
      In all participating centers, there will be a recruitment of index cases without family&#xD;
      screening to form a series of cases that will validate the results obtained in family forms.&#xD;
&#xD;
      The investigators will conduct genealogical trees of index cases to identify families, whose&#xD;
      number of healthy individuals and those with relevant PR makes sense for a family genetic&#xD;
      study, i.e. a genetically informative family.&#xD;
&#xD;
      In all centers, relatives of included Index cases, agreeing to participate in this research,&#xD;
      will be enrolled and followed.&#xD;
&#xD;
      Nantes University Hospital is the only center to perform a cold test (for reasons of&#xD;
      availability of the technique) but this test will be reserved for patients whose diagnosis of&#xD;
      primary Raynaud's phenomenon would be doubtful. Exposed identified relatives, agreeing to&#xD;
      participate in this research, will all be included and followed in their enrollment center.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 13, 2014</start_date>
  <completion_date type="Actual">June 10, 2020</completion_date>
  <primary_completion_date type="Actual">June 10, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To identify number of genes involved in vasospasm of primary Raynaud's phenomenon (RP) and determine the genetic cause of primary RP</measure>
    <time_frame>36 months</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine number of phenotypes associated to genotype of primary Raynaud's phenomenon</measure>
    <time_frame>36 months</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">258</enrollment>
  <condition>Primary Raynaud's Phenomenon (PR)</condition>
  <condition>Genetic Mutations Causing PR</condition>
  <condition>Study of Patients and Their Relatives (With or Without Primary PR)</condition>
  <arm_group>
    <arm_group_label>Patient with Raynaud's phenomenon</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>Demonstration of genetic mutations causing Raynaud's phenomenon</intervention_name>
    <description>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.&#xD;
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.&#xD;
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.</description>
    <arm_group_label>Patient with Raynaud's phenomenon</arm_group_label>
    <other_name>Recruitment of familial forms of Raynaud phenomenon (patients with primary</other_name>
    <other_name>Raynaud phenomenon and their relatives) to perform genetic analysis of</other_name>
    <other_name>exome sequencing type combined with an analysis of family bonding.</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Major Subject (age ≥ 18 years)&#xD;
&#xD;
          -  Index case with all the diagnostic criteria for primary Raynaud phenomenon, according&#xD;
             to current recommendations OR Related index case (relatives' patients) with or without&#xD;
             a primary Raynaud phenomenon.&#xD;
&#xD;
          -  Written consent to participate in the study&#xD;
&#xD;
          -  Written consent to participate in the collection of biological samples&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Subjects who have expressed their inability or refusal to sign an informed consent,&#xD;
&#xD;
          -  Index case with a secondary Raynaud phenomenon (suspected by clinical examination and&#xD;
             confirmed by capillaroscopy and laboratory tests: antinuclear antibody, abnormalities&#xD;
             of capillaroscopy mégacapillaire dystrophy or other major deviation).&#xD;
&#xD;
        (Criterion not applicable to related parties, i.e. family members of Index cases)&#xD;
&#xD;
        - Pregnant Woman.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marc-Antoine Pistorius, Prof</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital of Nantes</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marc-Antoine Pistorius, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of Nantes</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Luc Bressollette, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of Brest</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Patrick Jégo, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of Rennes</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Samir Henni, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital of Angers</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jean-Manuel Kubina, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital of La Roche/Yon</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Pierre Plissonneau Duquene, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital of St Nazaire</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU Angers - Service d'Explorations vasculaires</name>
      <address>
        <city>Angers</city>
        <zip>49033 Angers Cedex 01</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU HOPITAL CAVALE BLANCHE - Service de Médecine vasculaire</name>
      <address>
        <city>Brest</city>
        <zip>29609 Brest Cedex 2</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHD La Roche sur Yon - Service Angéiologie</name>
      <address>
        <city>La Roche sur Yon</city>
        <zip>85925 La Roche/Yon Cedex 9</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de NANTES - Service de Médecine Interne</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>C.H.R. HOPITAL SUD - Service de Médecine interne</name>
      <address>
        <city>Rennes</city>
        <zip>35203 Rennes Cedex 2</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ch Saint Nazaire</name>
      <address>
        <city>Saint Nazaire</city>
        <zip>44600</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 24, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Raynaud's phenomenon, Vasospasm, Genetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Raynaud Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02202291
org study id: RC14_0086
secondary id: 2014-A00470-47
nct id: NCT02202291
lead sponsor: 
has dmc: No
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).
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: 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
description: 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
measure: To determine number of phenotypes associated to genotype of primary Raynaud's phenomenon
time frame: 36 months
description: 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.
arm group label: Patient with Raynaud's phenomenon
arm group type: Experimental
intervention type: Genetic
intervention name: Demonstration of genetic mutations causing Raynaud's phenomenon
description: 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.
arm group label: Patient with Raynaud's phenomenon
other name: Recruitment of familial forms of Raynaud phenomenon (patients with primary
other name: Raynaud phenomenon and their relatives) to perform genetic analysis of
other name: exome sequencing type combined with an analysis of family bonding.
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Marc-Antoine Pistorius, Prof
role: Study Director
affiliation: University Hospital of Nantes
last name: Marc-Antoine Pistorius, Prof
role: Principal Investigator
affiliation: University Hospital of Nantes
last name: Luc Bressollette, Prof
role: Principal Investigator
affiliation: University Hospital of Brest
last name: Patrick Jégo, Prof
role: Principal Investigator
affiliation: University Hospital of Rennes
last name: Samir Henni, Dr
role: Principal Investigator
affiliation: University Hospital of Angers
last name: Jean-Manuel Kubina, Dr
role: Principal Investigator
affiliation: Hospital of La Roche/Yon
last name: Pierre Plissonneau Duquene, Dr
role: Principal Investigator
affiliation: Hospital of St Nazaire
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Raynaud Disease
sharing ipd: No