<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/NCT03774238</url>
  </required_header>
  <id_info>
    <org_study_id>UF7699</org_study_id>
    <nct_id>NCT03774238</nct_id>
  </id_info>
  <brief_title>Determinants of the Vascular Response to Training in Chronic Obstructive Pulmonary Disease (COPD) Patients</brief_title>
  <acronym>cDysEndoBPCO</acronym>
  <official_title>Biological and Functional Determinants of the Endothelial and Vascular Response to Exercise Training in COPD Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Hospital, Paris</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Montpellier</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>
      Vascular comorbidities constitute a major burden in COPD patients. The atherosclerosis&#xD;
      process is preceded by the onset of an endothelial dysfunction (assessed by the flow-mediated&#xD;
      dilatation (FMD)), which is a risk factor for later ischemic vascular complications and&#xD;
      death. In COPD, this endothelial dysfunction could be explained by intrinsic endothelial cell&#xD;
      properties, or the effect of a pathogenic endothelial cell microenvironment (inflammation&#xD;
      and/or oxidative stress). Exercise training constitue a powerful stimulus for the endothelial&#xD;
      function, and could be mediated by the mobiliaztion and function of endothelial progenitors.&#xD;
      While exercise training is an efficient intervention in COPD patients, its vascular effect&#xD;
      appear blunted. The endothelial function response to training has appeared heterogeneous in&#xD;
      COPD patients, and possibly linked to the endothelial cel lesion. Thus, endothelial function&#xD;
      (assessed by the FMD) response to exercise training would be lower in COPD patients with a&#xD;
      baseline impairment of the their FMD. In addition, of biological and functional factors could&#xD;
      explained the magnitude of the FMD response in COPD patients.The aim of the study are thus :&#xD;
&#xD;
      To compare the FMD change in COPD patients with FMD above (FMD+) and under the median FMD&#xD;
      (FMD-) after 4 weeks of exercise training in the whole study population.&#xD;
&#xD;
      To compare between COPD patients FMD+, COPD patients FMD- and healthy &quot;control&quot; subjects, the&#xD;
      endothelial inflammation and senescence at baseline and the endothelial progenitor&#xD;
      mobilization and function change induced by exercise (maximal exercise test and training).&#xD;
&#xD;
      To compare between COPD patients FMD+, COPD patients FMD- and healthy &quot;control&quot; subjects the&#xD;
      effect of the endothelial microenvironment on the cellular pathways regulating the&#xD;
      endothelial function in vitro at baseline and changes after exercise training.&#xD;
&#xD;
      To test in COPD patients the association between the magnitude of the FMD changes after&#xD;
      training and biological, functional and clinical factors (inflammation oxidative stress&#xD;
      markers, endothelial biomarkers, pulmonary impairment and phenotype, cardiovascular risks&#xD;
      factors, vascular function, metabolic markers, physical activity level, …)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 20, 2019</start_date>
  <completion_date type="Anticipated">May 20, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 20, 2023</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>
    <masking_description>COPD patient group (n=50) and Healthy control Group (n=24)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Measure of Flow-Mediated Dilatation (FMD)</measure>
    <time_frame>post exercise and after 4 +/- 2 weeks of training</time_frame>
    <description>Measure of FMD by EndoPAT2000©</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measure of biological vascular markers</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
    <description>E-selectin soluble (sE-sel), endotheline 1 (ET1), facteur von Willebrand (vWF), vascular endothelial growth factor A (VEGF-A), Fms-like tyrosine kinase receptor 1 soluble (sFlt-1), Angiopoietine 1 et 2 (Ang-1 Ang-2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of colonies and function of Endothelial-Colony Formaing cells (ECFC) in vitro</measure>
    <time_frame>post exercise and after 4 +/- 2 weeks of training</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number endothelial progenitors</measure>
    <time_frame>post exercise and after 4 +/- 2 weeks of training</time_frame>
    <description>CD34+, CD45+ and KDR + subpopulations by flow cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular function parameters</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
    <description>Systolic pressure index (in AU)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular function parameters</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
    <description>Intima-media thickness (in mm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular function parameters</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
    <description>Pulse-wave velocity (in ms-1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse-wave velocity (in ms-1)</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Markers of systemic inflammation</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
    <description>C-Reactive protein (in ng/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Markers of oxidative stress</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
    <description>Lipid peroxidation (in micromol/L)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle function parameters</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
    <description>Maximum isometric voluntary contraction (in N.m)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exercise capacity and vascular adaptation parameters</measure>
    <time_frame>after 4 +/- 2 weeks of training</time_frame>
    <description>Maximal oxygen uptake (VO2max, in mL/kg/min)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">74</enrollment>
  <condition>COPD Patients</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>COPD patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FMD analysis Endothelial progenitors Exercise test Exercise training</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy subject</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>FMD analysis Endothelial progenitors Exercise test</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>FMD analysis</intervention_name>
    <description>Blood sample and vascular exploration.</description>
    <arm_group_label>COPD patients</arm_group_label>
    <arm_group_label>Healthy subject</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        A/ COPD patients&#xD;
&#xD;
          -  age between 35 and 85 years old&#xD;
&#xD;
          -  spirometry showing an FEV1/VC &lt; lower limit of normal&#xD;
&#xD;
          -  with an indication for a pulmonary rehabilitation program&#xD;
&#xD;
          -  written and informed consent for this study signed by the patient&#xD;
&#xD;
        B/ Healthy subjects&#xD;
&#xD;
          -  age between 35 and 85 years old&#xD;
&#xD;
          -  no cardiovascular or respiratory disease&#xD;
&#xD;
          -  normal spirometry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unstabilized comorbidity&#xD;
&#xD;
          -  Subject in a period of exclusion relative to another protocol&#xD;
&#xD;
          -  Major protected by law&#xD;
&#xD;
          -  Subject participating in another research protocol&#xD;
&#xD;
          -  Subject not affiliated to a social security scheme&#xD;
&#xD;
          -  Pregnant or lactating woman&#xD;
&#xD;
          -  Patient deprived of freedom by court or administrative order&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fares Gouzi, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UH Montpellier</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fares Gouzi, MD, PhD</last_name>
    <phone>+33467335908</phone>
    <email>f-gouzi@chu-montpellier.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>CHU Montpellier and CHU Nimes</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fares Gouzi, MD, PhD</last_name>
      <phone>+33 4 67 33 59 08</phone>
      <email>f-gouzi@chu-montpellier.fr</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital, Paris</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Enrolling by invitation</status>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>October 30, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>August 18, 2023</last_update_submitted>
  <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Flow-mediated dilatation</keyword>
  <keyword>COPD</keyword>
  <keyword>Pulmonary Rehabilitation</keyword>
  <keyword>Comorbidities</keyword>
  <keyword>endothelial cell</keyword>
  <keyword>oxidative stress</keyword>
  <!-- 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/NCT03774238
org study id: UF7699
nct id: NCT03774238
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Vascular comorbidities constitute a major burden in COPD patients. The atherosclerosis
      process is preceded by the onset of an endothelial dysfunction (assessed by the flow-mediated
      dilatation (FMD)), which is a risk factor for later ischemic vascular complications and
      death. In COPD, this endothelial dysfunction could be explained by intrinsic endothelial cell
      properties, or the effect of a pathogenic endothelial cell microenvironment (inflammation
      and/or oxidative stress). Exercise training constitue a powerful stimulus for the endothelial
      function, and could be mediated by the mobiliaztion and function of endothelial progenitors.
      While exercise training is an efficient intervention in COPD patients, its vascular effect
      appear blunted. The endothelial function response to training has appeared heterogeneous in
      COPD patients, and possibly linked to the endothelial cel lesion. Thus, endothelial function
      (assessed by the FMD) response to exercise training would be lower in COPD patients with a
      baseline impairment of the their FMD. In addition, of biological and functional factors could
      explained the magnitude of the FMD response in COPD patients.The aim of the study are thus :

      To compare the FMD change in COPD patients with FMD above (FMD+) and under the median FMD
      (FMD-) after 4 weeks of exercise training in the whole study population.

      To compare between COPD patients FMD+, COPD patients FMD- and healthy "control" subjects, the
      endothelial inflammation and senescence at baseline and the endothelial progenitor
      mobilization and function change induced by exercise (maximal exercise test and training).

      To compare between COPD patients FMD+, COPD patients FMD- and healthy "control" subjects the
      effect of the endothelial microenvironment on the cellular pathways regulating the
      endothelial function in vitro at baseline and changes after exercise training.

      To test in COPD patients the association between the magnitude of the FMD changes after
      training and biological, functional and clinical factors (inflammation oxidative stress
      markers, endothelial biomarkers, pulmonary impairment and phenotype, cardiovascular risks
      factors, vascular function, metabolic markers, physical activity level, …)
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
masking description: COPD patient group (n=50) and Healthy control Group (n=24)
measure: Measure of Flow-Mediated Dilatation (FMD)
time frame: post exercise and after 4 +/- 2 weeks of training
description: Measure of FMD by EndoPAT2000©
measure: Measure of biological vascular markers
time frame: after 4 +/- 2 weeks of training
description: E-selectin soluble (sE-sel), endotheline 1 (ET1), facteur von Willebrand (vWF), vascular endothelial growth factor A (VEGF-A), Fms-like tyrosine kinase receptor 1 soluble (sFlt-1), Angiopoietine 1 et 2 (Ang-1 Ang-2)
measure: Number of colonies and function of Endothelial-Colony Formaing cells (ECFC) in vitro
time frame: post exercise and after 4 +/- 2 weeks of training
measure: Number endothelial progenitors
time frame: post exercise and after 4 +/- 2 weeks of training
description: CD34+, CD45+ and KDR + subpopulations by flow cytometry
measure: Vascular function parameters
time frame: after 4 +/- 2 weeks of training
description: Systolic pressure index (in AU)
measure: Vascular function parameters
time frame: after 4 +/- 2 weeks of training
description: Intima-media thickness (in mm)
measure: Vascular function parameters
time frame: after 4 +/- 2 weeks of training
description: Pulse-wave velocity (in ms-1)
measure: Pulse-wave velocity (in ms-1)
time frame: after 4 +/- 2 weeks of training
measure: Markers of systemic inflammation
time frame: after 4 +/- 2 weeks of training
description: C-Reactive protein (in ng/ml)
measure: Markers of oxidative stress
time frame: after 4 +/- 2 weeks of training
description: Lipid peroxidation (in micromol/L)
measure: Muscle function parameters
time frame: after 4 +/- 2 weeks of training
description: Maximum isometric voluntary contraction (in N.m)
measure: Exercise capacity and vascular adaptation parameters
time frame: after 4 +/- 2 weeks of training
description: Maximal oxygen uptake (VO2max, in mL/kg/min)
arm group label: COPD patients
arm group type: Experimental
description: FMD analysis Endothelial progenitors Exercise test Exercise training
arm group label: Healthy subject
arm group type: Experimental
description: FMD analysis Endothelial progenitors Exercise test
intervention type: Other
intervention name: FMD analysis
description: Blood sample and vascular exploration.
arm group label: COPD patients
arm group label: Healthy subject
criteria: 
gender: All
minimum age: 35 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Fares Gouzi, MD, PhD
role: Principal Investigator
affiliation: UH Montpellier
last name: Fares Gouzi, MD, PhD
phone: +33467335908
email: f-gouzi@chu-montpellier.fr
facility: 
status: Recruiting
contact: 
facility: 
status: Enrolling by invitation
country: France
responsible party type: Sponsor