<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/NCT04451785</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL19_0949</org_study_id>
    <secondary_id>2019-A03203-54</secondary_id>
    <nct_id>NCT04451785</nct_id>
  </id_info>
  <brief_title>Hereditary Spherocytosis and Vascular Function</brief_title>
  <acronym>VASCUSPHERO</acronym>
  <official_title>Relationships Between Hemolysis, Erythrosis, Circulating Microparticles and Vascular Function in Patients With Hereditary Spherocytosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</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>
      Background : Patients with hereditary spherocytosis (HS) are characterized by increased red&#xD;
      blood cell (RBC) fragility and a loss of RBC deformability. While the clinical variability of&#xD;
      the disease may be heterogenous from one patient to another, some studies reported the&#xD;
      occurrence of vascular complications, notably in patients who have been splenectomized.&#xD;
&#xD;
      Purpose : The aim of the study is to test the associations between the degree of vascular&#xD;
      dysfunction and the extent of hemolysis, the amount of circulating microparticles, the level&#xD;
      of erythrosis and the degree of RBC biophysical alterations.&#xD;
&#xD;
      Abstract : Recent studies reported the occurrence of vascular complications in patients with&#xD;
      HS, notably in patients who have previously been splenectomized. However, the exact reasons&#xD;
      of these complications are unknown and no study investigated the vascular function in HS&#xD;
      patients.&#xD;
&#xD;
      Main objective Highlight the presence of altered vascular function in HS patients and test&#xD;
      the relationships with the level of hemolysis and circulating microparticles.&#xD;
&#xD;
      Secondary objectives To evaluate the associations between clinical severity and 1) the level&#xD;
      of vascular dysfunction and 2) several biomarkers (hemolysis, hematological parameters,&#xD;
      circulating microparticles, erythrosis, RBC biophysical properties).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 26, 2020</start_date>
  <completion_date type="Anticipated">August 26, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 26, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>measurement of pulse wave velocity (PWV)</measure>
    <time_frame>Day 1</time_frame>
    <description>Vascular function (arterial stiffness) will be investigated by the measurement of pulse wave velocity (PWV). Vascular dysfunction will be defined by a PWV value higher than 6 meter/second (m/s) and 10 m/s in children and adults with HS, respectively.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hemogram</measure>
    <time_frame>Day 1</time_frame>
    <description>The hemogram is a complete blood count of the different cell types. All these measures are performed simultaneously on a standard hematology analyzer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Markers of hemolysis</measure>
    <time_frame>Day 1</time_frame>
    <description>These markers are measured simultaneously on a standard biochemistry analyzer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulating microparticles</measure>
    <time_frame>Day 1</time_frame>
    <description>Circulating microparticles of various cell origin will be measured by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Markers of erythrosis</measure>
    <time_frame>Day 1</time_frame>
    <description>Markers of erythrosis (i.e., suicidal death of red blood cells) will be measured by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood viscosity</measure>
    <time_frame>Day 1</time_frame>
    <description>Blood viscosity (expressed in Pa.s) will be measured on a cone-plate viscosimeter, ektacytometry and light transmission, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Red blood cell deformability</measure>
    <time_frame>Day 1</time_frame>
    <description>Red blood cell deformability will be measured simultaneously on a Lorrca ektacytometry (Laser-assisted Rotational Red Cell Analyser).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Red blood cell aggregation</measure>
    <time_frame>Day 1</time_frame>
    <description>Red blood cell aggregation will be measured simultaneously on a Lorrca ektacytometry (Laser-assisted Rotational Red Cell Analyser).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Hereditary Spherocytosis</condition>
  <arm_group>
    <arm_group_label>Healthy individuals</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 healthy subjets aged 6 years minimum will be included in this study. This is the control group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with hereditary spherocytosis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60 patients with hereditary spherocytosis will be included in this study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>blood sample</intervention_name>
    <description>6 tubes of 4 milliliters (ml) maximum (total: 24 ml) will be sampled for the measurements of the different biological markers. In case of the genetic mutation is already known, only 5 tubes will be collected (total: 20 ml).</description>
    <arm_group_label>Healthy individuals</arm_group_label>
    <arm_group_label>Patients with hereditary spherocytosis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Pulse wave velocity</intervention_name>
    <description>Non-invasive measurement of pulse wave velocity between the carotid and femoral arteries with piezo-electric sensors.</description>
    <arm_group_label>Healthy individuals</arm_group_label>
    <arm_group_label>Patients with hereditary spherocytosis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Healthy controls:&#xD;
&#xD;
          -  age ≥ 6 years old&#xD;
&#xD;
          -  written, informed and signed consent by the healthy volunteer, or by both parents or&#xD;
             legal guardian if the healthy volunteer is a minor&#xD;
&#xD;
          -  Healthy volunteer affiliated to a social security scheme or assimilated&#xD;
&#xD;
          -  Healthy volunteer not subject to any legal protection measure&#xD;
&#xD;
        Patients with hereditary spherocytosis:&#xD;
&#xD;
          -  age ≥ 6 years old&#xD;
&#xD;
          -  Patient with hereditary or non-splenectomized spherocytosis&#xD;
&#xD;
          -  Written, informed and signed consent by the patient, or by at least one of the two&#xD;
             parents or legal guardian if the patient is a minor&#xD;
&#xD;
          -  Patient affiliated to a social security scheme or assimilated&#xD;
&#xD;
          -  Patient not subject to any legal protection measure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Healthy controls:&#xD;
&#xD;
          -  Pregnant or lactating woman&#xD;
&#xD;
          -  Subjects with hereditary spherocytosis or other characterized condition by chronic&#xD;
             hemolysis&#xD;
&#xD;
          -  Subjects with known pathology affecting the vascular system&#xD;
&#xD;
          -  Blood donation (less than a month old)&#xD;
&#xD;
          -  Not affiliated to a social security scheme&#xD;
&#xD;
          -  Patient participating in another interventional research protocol that may interfere&#xD;
             with this protocol (according to the investigator's judgment).&#xD;
&#xD;
        Patients with hereditary spherocytosis:&#xD;
&#xD;
          -  Patient who received a blood transfusion in the 3 months preceding&#xD;
&#xD;
          -  Pregnant or lactating woman&#xD;
&#xD;
          -  Any disease or condition other than hereditary spherocytosis, chronic or not, likely&#xD;
             to induce chronic or acute intravascular hemolysis&#xD;
&#xD;
          -  Patient participating in another interventional research protocol that may interfere&#xD;
             with this protocol (according to the investigator's judgment).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Alexandra GAUTHIER-VASSEROT, MD,PHD</last_name>
    <phone>04 69 16 65 72</phone>
    <phone_ext>+33</phone_ext>
    <email>alexandra.gauthier@ihope.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Philippe CONNES</last_name>
    <phone>04 72 43 16 25</phone>
    <phone_ext>+33</phone_ext>
    <email>philippe.connes@univ-lyon1.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Institut d'Hématologie et Oncologie PEdiatrique (iHOPe)</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alexandra GAUTHIER-VASSEROT, MD,PhD</last_name>
      <phone>04 69 16 65 72</phone>
      <phone_ext>+33</phone_ext>
      <email>alexandra.gauthier@ihope.fr</email>
    </contact>
    <investigator>
      <last_name>Alexandra GAUTHIER-VASSEROT, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yves BERTRAND, PU,PH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kamila KEBAILI, MD,PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Céline RENARD, MD,PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nathalie GARNIER, MD,PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <zip>69437</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giovanna CANNAS, MD,PhD</last_name>
      <phone>04 72 11 74 12</phone>
      <phone_ext>+33</phone_ext>
      <email>giovanna.cannas@chu-lyon.fr</email>
    </contact>
    <investigator>
      <last_name>Giovanna CANNAS, MD,PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Arnaud HOT, PU,PH</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Romain FORT, MD,PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Solène POUTREL, MD,PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>March 15, 2022</last_update_submitted>
  <last_update_submitted_qc>March 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hereditary spherocytosis</keyword>
  <keyword>hemolysis</keyword>
  <keyword>microparticles</keyword>
  <keyword>vascular function</keyword>
  <keyword>red blood cell</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spherocytosis, Hereditary</mesh_term>
  </condition_browse>
  <!-- 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/NCT04451785
org study id: 69HCL19_0949
secondary id: 2019-A03203-54
nct id: NCT04451785
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background : Patients with hereditary spherocytosis (HS) are characterized by increased red
      blood cell (RBC) fragility and a loss of RBC deformability. While the clinical variability of
      the disease may be heterogenous from one patient to another, some studies reported the
      occurrence of vascular complications, notably in patients who have been splenectomized.

      Purpose : The aim of the study is to test the associations between the degree of vascular
      dysfunction and the extent of hemolysis, the amount of circulating microparticles, the level
      of erythrosis and the degree of RBC biophysical alterations.

      Abstract : Recent studies reported the occurrence of vascular complications in patients with
      HS, notably in patients who have previously been splenectomized. However, the exact reasons
      of these complications are unknown and no study investigated the vascular function in HS
      patients.

      Main objective Highlight the presence of altered vascular function in HS patients and test
      the relationships with the level of hemolysis and circulating microparticles.

      Secondary objectives To evaluate the associations between clinical severity and 1) the level
      of vascular dysfunction and 2) several biomarkers (hemolysis, hematological parameters,
      circulating microparticles, erythrosis, RBC biophysical properties).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: measurement of pulse wave velocity (PWV)
time frame: Day 1
description: Vascular function (arterial stiffness) will be investigated by the measurement of pulse wave velocity (PWV). Vascular dysfunction will be defined by a PWV value higher than 6 meter/second (m/s) and 10 m/s in children and adults with HS, respectively.
measure: Hemogram
time frame: Day 1
description: The hemogram is a complete blood count of the different cell types. All these measures are performed simultaneously on a standard hematology analyzer.
measure: Markers of hemolysis
time frame: Day 1
description: These markers are measured simultaneously on a standard biochemistry analyzer
measure: Circulating microparticles
time frame: Day 1
description: Circulating microparticles of various cell origin will be measured by flow cytometry
measure: Markers of erythrosis
time frame: Day 1
description: Markers of erythrosis (i.e., suicidal death of red blood cells) will be measured by flow cytometry
measure: Blood viscosity
time frame: Day 1
description: Blood viscosity (expressed in Pa.s) will be measured on a cone-plate viscosimeter, ektacytometry and light transmission, respectively.
measure: Red blood cell deformability
time frame: Day 1
description: Red blood cell deformability will be measured simultaneously on a Lorrca ektacytometry (Laser-assisted Rotational Red Cell Analyser).
measure: Red blood cell aggregation
time frame: Day 1
description: Red blood cell aggregation will be measured simultaneously on a Lorrca ektacytometry (Laser-assisted Rotational Red Cell Analyser).
arm group label: Healthy individuals
arm group type: Active Comparator
description: 20 healthy subjets aged 6 years minimum will be included in this study. This is the control group.
arm group label: Patients with hereditary spherocytosis
arm group type: Experimental
description: 60 patients with hereditary spherocytosis will be included in this study.
intervention type: Biological
intervention name: blood sample
description: 6 tubes of 4 milliliters (ml) maximum (total: 24 ml) will be sampled for the measurements of the different biological markers. In case of the genetic mutation is already known, only 5 tubes will be collected (total: 20 ml).
arm group label: Healthy individuals
arm group label: Patients with hereditary spherocytosis
intervention type: Diagnostic Test
intervention name: Pulse wave velocity
description: Non-invasive measurement of pulse wave velocity between the carotid and femoral arteries with piezo-electric sensors.
arm group label: Healthy individuals
arm group label: Patients with hereditary spherocytosis
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Alexandra GAUTHIER-VASSEROT, MD,PHD
phone: 04 69 16 65 72
phone ext: +33
email: alexandra.gauthier@ihope.fr
last name: Philippe CONNES
phone: 04 72 43 16 25
phone ext: +33
email: philippe.connes@univ-lyon1.fr
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Spherocytosis, Hereditary