<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/NCT04463212</url>
  </required_header>
  <id_info>
    <org_study_id>RC20_0280</org_study_id>
    <nct_id>NCT04463212</nct_id>
  </id_info>
  <brief_title>Endothelial Dysfunction in Reversible Cerebral Vasoconstriction Syndrome</brief_title>
  <acronym>DESS</acronym>
  <official_title>Systemic Endothelial Dysfunction in Reversible Cerebral Vasoconstriction Syndrome : a Case Control Study</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a syndrome described at the end of&#xD;
      the 20th century. Generally, it has a benign course. It is revealed by acute headaches, in&#xD;
      different circumstances such as sexual activity, physical exertion or emotional disturbances.&#xD;
      But, in few cases, it might be complicated by seizure, stroke and subarachnoid haemorrhage.&#xD;
      The diagnosis is confirmed on radiological examination, which shows diffuse cerebral&#xD;
      vasoconstriction of brain vessel. It calls reversible because at three month,&#xD;
      vasoconstriction disappears. Most cases occur during post partum or after&#xD;
      serotoninergic/adrenergic drug use. The pathophysiology is unknown but a transient&#xD;
      disturbance in the control of cerebrovascular tone by sympathic hyperactivity and/or&#xD;
      endothelial dysfunction are suspected. The assessment of endothelial dysfunction in brain is&#xD;
      possible with transcranial doppler. Chen et al. showed an impairment of vasodilatation post&#xD;
      apnea induced called BHI on RCVS subjects compared with healthy control. BHI is a reflect of&#xD;
      endothelial function in brain. Currently, investigators do not know if endothelial&#xD;
      dysfunction occurred only in brain or if it may occur in systemic vessel. Some case reports&#xD;
      talk about systemic complication such as kidney infarct or hepatic arterial vasospasm so a&#xD;
      systemic vascular dysfunction may be suspected. In this study, researchers will study&#xD;
      systemic endothelial function by measure of the pulse wave velocity during RCVS and after its&#xD;
      recovering at 3 months, and compare it at healthy controls.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators lead a case control study to find a systemic endothelial dysfunction by the&#xD;
      using of Complior device. Complior is a mechanographer who calculates pulse wave velocity&#xD;
      (PWV). Pulse wave velocity is a reflect of arterial stiffness and it's correlate with&#xD;
      endothelial dysfunction. For BHI, a Philips echograph is used before and after 30 second of&#xD;
      breath holding.&#xD;
&#xD;
      Study protocol is :&#xD;
&#xD;
      For Patient :&#xD;
&#xD;
        -  Day 0 : in hospital : anamnesis, medical history, physic examination, EKG, blood sample&#xD;
           analysis, BHI, PWV analysis&#xD;
&#xD;
        -  Month 1 : in medical visit : medical evolution, physic examination, EKG, blood sample&#xD;
           analysis, BHI, PWV analysis&#xD;
&#xD;
        -  Month 3 : in medical visit : medical evolution, physic examination, EKG, blood sample&#xD;
           analysis, BHI, PWV analysis, cerebral angioCT Scan&#xD;
&#xD;
      For control :&#xD;
&#xD;
      - Day 0 : in hospital : medical history, physic examination, EKG, BHI, PWV analysis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 29, 2021</start_date>
  <completion_date type="Anticipated">January 1, 2024</completion_date>
  <primary_completion_date type="Actual">January 29, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Compare systemic endothelial function between patient and healthy subject</measure>
    <time_frame>24 hours</time_frame>
    <description>By using Complior, researchers assess systemic endothelial function at inclusion on patient and healthy volunteer person by pulse wave velocity (cm.s-1)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>BHI (Breath Holding Index)</measure>
    <time_frame>at day 0, month 1, month 3</time_frame>
    <description>BHI measure on middle cerebral arteries by transcranial ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse wave velocity (PWV)</measure>
    <time_frame>at day 0, month 1, month 3</time_frame>
    <description>Pulse wave velocity mesaure from carotid to femoral artery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship between cerebral and systemic endothelial function</measure>
    <time_frame>at day 0, month 1, month 3</time_frame>
    <description>Comparison of BHI and VOP evolution</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal failure</measure>
    <time_frame>Day 0</time_frame>
    <description>Diminution of creatinin clearance&lt;100 ml/min/1.73m2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurence of stroke or cerebral oedema</measure>
    <time_frame>at day 0, month 1, month 3</time_frame>
    <description>Occurrence of ischemic stroke, cerebral haemorrhage, cerebral oedema</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of PWV between patients with or without arterial hypertension</measure>
    <time_frame>at day 0, month 1, month 3</time_frame>
    <description>Comparison between middle PWV (cm/s) of patients with arterial hypertension and patients without arterial hypertension</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison of BHI between patients with or without arterial hypertension</measure>
    <time_frame>at day 0, month 1, month 3</time_frame>
    <description>Comparison between middle BHI of patients with arterial hypertension and patients without arterial hypertension</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison between PWV (cm/s)</measure>
    <time_frame>at 3 months</time_frame>
    <description>Comparison between PWV (cm/s) between patients and control group</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Comparison between BHI (cm/s)</measure>
    <time_frame>at 3 months</time_frame>
    <description>Comparison between BHI (cm/s) between patients and control group</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">62</enrollment>
  <condition>Reversible Cerebral Vasoconstriction Syndrome</condition>
  <arm_group>
    <arm_group_label>Patient</arm_group_label>
    <description>Diagnosis of probable SVCR evoked, faced with a single or repeated episode of unusual thunderclap or rapidly progressive headache, and demonstration of diffuse vasospasms via sectional imaging (angiography, angio-MRI or cerebral arteriography) or an increase in transcranial doppler speeds</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Subject control</arm_group_label>
    <description>Subject without SVCR (current and history)</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients and Healthy subjects&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria for patients :&#xD;
&#xD;
          -  Aged from 18 to 80 years old&#xD;
&#xD;
          -  RVCS diagnosis evoked on clinic and radiologic finding&#xD;
&#xD;
          -  Last headache was 15 days ago&#xD;
&#xD;
          -  Oral consent&#xD;
&#xD;
          -  Register in French social security&#xD;
&#xD;
        Inclusion criteria for control :&#xD;
&#xD;
          -  Aged from 18 to 80 years old&#xD;
&#xD;
          -  Hypothesis of RCVS in clinical presentation and on cerebral imaging&#xD;
&#xD;
          -  Last headache less than 3 days old&#xD;
&#xD;
          -  Oral consent&#xD;
&#xD;
          -  Register in French social security&#xD;
&#xD;
          -  Person under guardianship, curatorship or safeguarding of justice&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Non inclusion criteria for patient :&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Tobacco, coffee, alcohol, drugs or vasoactive recreational substances use within 2&#xD;
             hours prior to the examination.&#xD;
&#xD;
          -  Person under guardianship, curatorship or safeguarding of justice&#xD;
&#xD;
          -  Non sinusal rhythm on EKG&#xD;
&#xD;
          -  Impossible of Breath holding for 30 secondes&#xD;
&#xD;
        Exclusion criteria for patient :&#xD;
&#xD;
        - No reversibility at 3 months&#xD;
&#xD;
        Non inclusion criteria for control :&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Tobacco, coffee, alcohol, drugs or vasoactive recreational substances use within 2&#xD;
             hours prior to the examination.&#xD;
&#xD;
          -  Non sinusal rhythm on EKG&#xD;
&#xD;
          -  Impossible of Breath holding for 30 secondes&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Solène DE GAALON, PhD</last_name>
    <phone>02 40 16 52 12</phone>
    <email>Solene.DEGAALON@chu-nantes.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Annick COULON</last_name>
    <phone>02 53 48 28 35</phone>
    <email>bp-prom-regl@chu-nantes.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Nantes University Hospital</name>
      <address>
        <city>Nantes</city>
        <state>Loire-Atlantique</state>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Solene DE GAALON, PH</last_name>
      <phone>33240165212</phone>
      <email>solene.degaalon@chu-nantes.fr</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 3, 2020</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>March 16, 2023</last_update_submitted>
  <last_update_submitted_qc>March 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Endothelial dysfunction</keyword>
  <keyword>Reversible cerebral vasoconstriction syndrome</keyword>
  <keyword>Arterial stiffness</keyword>
  <keyword>Breath holding index</keyword>
  <keyword>Pulse wave velocity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Syndrome</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/NCT04463212
org study id: RC20_0280
nct id: NCT04463212
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Reversible Cerebral Vasoconstriction Syndrome (RCVS) is a syndrome described at the end of
      the 20th century. Generally, it has a benign course. It is revealed by acute headaches, in
      different circumstances such as sexual activity, physical exertion or emotional disturbances.
      But, in few cases, it might be complicated by seizure, stroke and subarachnoid haemorrhage.
      The diagnosis is confirmed on radiological examination, which shows diffuse cerebral
      vasoconstriction of brain vessel. It calls reversible because at three month,
      vasoconstriction disappears. Most cases occur during post partum or after
      serotoninergic/adrenergic drug use. The pathophysiology is unknown but a transient
      disturbance in the control of cerebrovascular tone by sympathic hyperactivity and/or
      endothelial dysfunction are suspected. The assessment of endothelial dysfunction in brain is
      possible with transcranial doppler. Chen et al. showed an impairment of vasodilatation post
      apnea induced called BHI on RCVS subjects compared with healthy control. BHI is a reflect of
      endothelial function in brain. Currently, investigators do not know if endothelial
      dysfunction occurred only in brain or if it may occur in systemic vessel. Some case reports
      talk about systemic complication such as kidney infarct or hepatic arterial vasospasm so a
      systemic vascular dysfunction may be suspected. In this study, researchers will study
      systemic endothelial function by measure of the pulse wave velocity during RCVS and after its
      recovering at 3 months, and compare it at healthy controls.
The investigators lead a case control study to find a systemic endothelial dysfunction by the
      using of Complior device. Complior is a mechanographer who calculates pulse wave velocity
      (PWV). Pulse wave velocity is a reflect of arterial stiffness and it's correlate with
      endothelial dysfunction. For BHI, a Philips echograph is used before and after 30 second of
      breath holding.

      Study protocol is :

      For Patient :

        -  Day 0 : in hospital : anamnesis, medical history, physic examination, EKG, blood sample
           analysis, BHI, PWV analysis

        -  Month 1 : in medical visit : medical evolution, physic examination, EKG, blood sample
           analysis, BHI, PWV analysis

        -  Month 3 : in medical visit : medical evolution, physic examination, EKG, blood sample
           analysis, BHI, PWV analysis, cerebral angioCT Scan

      For control :

      - Day 0 : in hospital : medical history, physic examination, EKG, BHI, PWV analysis
observational model: Case-Only
time perspective: Prospective
measure: Compare systemic endothelial function between patient and healthy subject
time frame: 24 hours
description: By using Complior, researchers assess systemic endothelial function at inclusion on patient and healthy volunteer person by pulse wave velocity (cm.s-1)
measure: BHI (Breath Holding Index)
time frame: at day 0, month 1, month 3
description: BHI measure on middle cerebral arteries by transcranial ultrasound
measure: Pulse wave velocity (PWV)
time frame: at day 0, month 1, month 3
description: Pulse wave velocity mesaure from carotid to femoral artery
measure: Relationship between cerebral and systemic endothelial function
time frame: at day 0, month 1, month 3
description: Comparison of BHI and VOP evolution
measure: Renal failure
time frame: Day 0
description: Diminution of creatinin clearance<100 ml/min/1.73m2
measure: Occurence of stroke or cerebral oedema
time frame: at day 0, month 1, month 3
description: Occurrence of ischemic stroke, cerebral haemorrhage, cerebral oedema
measure: Comparison of PWV between patients with or without arterial hypertension
time frame: at day 0, month 1, month 3
description: Comparison between middle PWV (cm/s) of patients with arterial hypertension and patients without arterial hypertension
measure: Comparison of BHI between patients with or without arterial hypertension
time frame: at day 0, month 1, month 3
description: Comparison between middle BHI of patients with arterial hypertension and patients without arterial hypertension
measure: Comparison between PWV (cm/s)
time frame: at 3 months
description: Comparison between PWV (cm/s) between patients and control group
measure: Comparison between BHI (cm/s)
time frame: at 3 months
description: Comparison between BHI (cm/s) between patients and control group
arm group label: Patient
description: Diagnosis of probable SVCR evoked, faced with a single or repeated episode of unusual thunderclap or rapidly progressive headache, and demonstration of diffuse vasospasms via sectional imaging (angiography, angio-MRI or cerebral arteriography) or an increase in transcranial doppler speeds
arm group label: Subject control
description: Subject without SVCR (current and history)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Solène DE GAALON, PhD
phone: 02 40 16 52 12
email: Solene.DEGAALON@chu-nantes.fr
last name: Annick COULON
phone: 02 53 48 28 35
email: bp-prom-regl@chu-nantes.fr
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Sponsor
mesh term: Syndrome
sharing ipd: No