<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/NCT04448626</url>
  </required_header>
  <id_info>
    <org_study_id>RECHMPL20_0137</org_study_id>
    <nct_id>NCT04448626</nct_id>
  </id_info>
  <brief_title>Micro-environment Involvement in Muscle Alteration Induced</brief_title>
  <acronym>MicAMI-BPCO</acronym>
  <official_title>Micro-environment Involvement in Muscle Alteration Induced by Copd Exacerbation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Montpellier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>APARD Fonds de dotation</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>
      Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent airway&#xD;
      obstruction and inflammatory response of the lungs and bronchi. Episodes of exacerbations&#xD;
      contribute to increase the severity and prognosis of the disease. Muscle dysfunction (loss of&#xD;
      strengh and muscle mass) is one of comorbidities affecting 30% to 60% of patients and playing&#xD;
      a key role in their prognosis. During exacerbation, some studies have suggested an&#xD;
      association between muscle dysfunction and modifications of inflammatory circulating factors&#xD;
      such as CRP, TNF-alpha, IL- 6, IL8, but no exhaustive study has identified precisely one (or&#xD;
      more) biomarker(s) that can induce this muscle wasting during the exacerbation of COPD. Our&#xD;
      hypothesis is that the serum of exacerbated COPD patients represents a deleterious&#xD;
      microenvironment for the muscle cells which would amplify the mechanisms of atrophy linked to&#xD;
      hospitalization. Our team has already developed a cell culture model to study the effects of&#xD;
      the plasma microenvironment on atrophy of cultured myotubes. The investigators have shown&#xD;
      that the serum of COPD patients can induce muscle atrophy.&#xD;
&#xD;
      The objectives of this study are : 1/ to evaluate the effects of circulating pro-inflammatory&#xD;
      factors on atrophy and the myogenic capacities of muscle cells; and 2/ to identify one (or&#xD;
      more) circulating biomarker (s) that may be responsible for the muscle damage induced by the&#xD;
      microenvironment of hospitalized patients for exacerbation of COPD. First, myotubes and&#xD;
      myoblasts of healthy subjects will be cultivated with 9 exacerbation copd patient serum or 9&#xD;
      copd patient serum or 9 healthy subject serum. Myotube diameters, atrophy, inflammatory and&#xD;
      oxidative stress markers and alteration of the myogenic capacity of satellite cells will be&#xD;
      compared between three groups. Second, the differential expression of circulating&#xD;
      proinflammatory molecules will be compared in the serum of the three groups. Identifying&#xD;
      circulating factors associated with muscle weakness is a necessary step to better understand&#xD;
      the mechanisms and consider a personalized therapeutic approach that can improve the&#xD;
      functional and clinical prognosis of disease.&#xD;
&#xD;
      .&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2020</start_date>
  <completion_date type="Actual">May 30, 2020</completion_date>
  <primary_completion_date type="Actual">May 1, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Effects evaluation of circulating pro-inflammatory factors on atrophy</measure>
    <time_frame>6 months</time_frame>
    <description>Atrophy marker evaluation in cultured muscle cells (myotubes)&#xD;
cultured myotube diameter exposed to the three serum groups (immunofluorescence)&#xD;
atrophy (ubiquitin proteasome system, proteolytic autophagy pathway), inflammatory (TNF-alpha, IL-6, IL-8…) and oxidative stress (ROS, lipid peroxidation) markers expressed by cells exposed to the three serum groups (PCR et WesternBlot)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effects evaluation of circulating pro-inflammatory factors on the myogenic capacities of muscle cells</measure>
    <time_frame>6 months</time_frame>
    <description>Myogenic capacities of cultured muscle cells (myoblastes)&#xD;
inflammatory (TNF-alpha, IL-6, IL-8…) and oxidative stress (ROS, lipid peroxidation) markers expressed by cells exposed to the three serum groups (PCR et WesternBlot)&#xD;
regeneration markers (Notch and myogenesis signaling pathways) expressed by cells exposed to the three serum groups (PCR et WesternBlot)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Identification of one (or more) circulating biomarker (s)</measure>
    <time_frame>3 months</time_frame>
    <description>Identification of one (or more) circulating biomarker (s) that may be responsible for the muscle alteration induced by the microenvironment of patient in exacerbation of COPD</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">27</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <condition>Exacerbations</condition>
  <condition>Skeletal Muscle Atrophy</condition>
  <arm_group>
    <arm_group_label>Healthy subject</arm_group_label>
    <description>Healthy subject</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stable COPD patients</arm_group_label>
    <description>Stable COPD patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exacerbation COPD patients</arm_group_label>
    <description>Exacerbation COPD patients</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      serum&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        COPD patients hospitalized for exacerbation in Montpellier university hospital, France.&#xD;
&#xD;
        COPD patients recruited in Clinique du Souffle, La Vallonie, Lodève, France. Healthy&#xD;
        volunteer subject recruited in Clinique du Souffle, La Vallonie, Lodève, France.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion criteria 1/ for COPD patients hospitalized for exacerbation:&#xD;
&#xD;
          -  Hospitalization for COPD exacerbation 2/ for COPD patients&#xD;
&#xD;
          -  COPD patients GOLD II à IV&#xD;
&#xD;
          -  Not having followed respiratory réhabilitation stay for at least one year 3/ for&#xD;
             Healthy subjects&#xD;
&#xD;
          -  healthy and sedentary (Voorips score &lt;9)&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. for COPD patients hospitalized for exacerbation:&#xD;
&#xD;
               -  concomitant acute cardiac évent&#xD;
&#xD;
               -  trachéal intubation with mechanical ventilation&#xD;
&#xD;
               -  chronic respiratory disease other than COPD&#xD;
&#xD;
               -  locomotor, neurologic or psychiatric comorbidities&#xD;
&#xD;
          2. for COPD patients&#xD;
&#xD;
               -  Exacerbation with récent hospitalization (&lt;4 weeks)&#xD;
&#xD;
               -  Neurologic comorbidity&#xD;
&#xD;
          3. for Healthy subjects - long term drug treatment with proven central effects&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maurice HAYOT, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital, Montpellier</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Uhmontpellier</name>
      <address>
        <city>Montpellier</city>
        <zip>34295</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Spruit MA, Gosselink R, Troosters T, Kasran A, Gayan-Ramirez G, Bogaerts P, Bouillon R, Decramer M. Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Thorax. 2003 Sep;58(9):752-6. doi: 10.1136/thorax.58.9.752.</citation>
    <PMID>12947130</PMID>
  </reference>
  <reference>
    <citation>Crul T, Testelmans D, Spruit MA, Troosters T, Gosselink R, Geeraerts I, Decramer M, Gayan-Ramirez G. Gene expression profiling in vastus lateralis muscle during an acute exacerbation of COPD. Cell Physiol Biochem. 2010;25(4-5):491-500. doi: 10.1159/000303054. Epub 2010 Mar 23.</citation>
    <PMID>20332630</PMID>
  </reference>
  <reference>
    <citation>Crul T, Spruit MA, Gayan-Ramirez G, Quarck R, Gosselink R, Troosters T, Pitta F, Decramer M. Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients. Eur J Clin Invest. 2007 Nov;37(11):897-904. doi: 10.1111/j.1365-2362.2007.01867.x. Epub 2007 Sep 20.</citation>
    <PMID>17883420</PMID>
  </reference>
  <reference>
    <citation>Catteau M, Gouzi F, Blervaque L, Passerieux E, Blaquiere M, Ayoub B, Bughin F, Mercier J, Hayot M, Pomies P. Effects of a human microenvironment on the differentiation of human myoblasts. Biochem Biophys Res Commun. 2020 May 14;525(4):968-973. doi: 10.1016/j.bbrc.2020.03.020. Epub 2020 Mar 12.</citation>
    <PMID>32173533</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 15, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</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 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD Exacerbation</keyword>
  <keyword>Muscle atrophy</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Oxidative stress</keyword>
  <keyword>Biomarkers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
    <mesh_term>Muscular Atrophy</mesh_term>
    <mesh_term>Atrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>NC</ipd_description>
  </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/NCT04448626
org study id: RECHMPL20_0137
nct id: NCT04448626
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent airway
      obstruction and inflammatory response of the lungs and bronchi. Episodes of exacerbations
      contribute to increase the severity and prognosis of the disease. Muscle dysfunction (loss of
      strengh and muscle mass) is one of comorbidities affecting 30% to 60% of patients and playing
      a key role in their prognosis. During exacerbation, some studies have suggested an
      association between muscle dysfunction and modifications of inflammatory circulating factors
      such as CRP, TNF-alpha, IL- 6, IL8, but no exhaustive study has identified precisely one (or
      more) biomarker(s) that can induce this muscle wasting during the exacerbation of COPD. Our
      hypothesis is that the serum of exacerbated COPD patients represents a deleterious
      microenvironment for the muscle cells which would amplify the mechanisms of atrophy linked to
      hospitalization. Our team has already developed a cell culture model to study the effects of
      the plasma microenvironment on atrophy of cultured myotubes. The investigators have shown
      that the serum of COPD patients can induce muscle atrophy.

      The objectives of this study are : 1/ to evaluate the effects of circulating pro-inflammatory
      factors on atrophy and the myogenic capacities of muscle cells; and 2/ to identify one (or
      more) circulating biomarker (s) that may be responsible for the muscle damage induced by the
      microenvironment of hospitalized patients for exacerbation of COPD. First, myotubes and
      myoblasts of healthy subjects will be cultivated with 9 exacerbation copd patient serum or 9
      copd patient serum or 9 healthy subject serum. Myotube diameters, atrophy, inflammatory and
      oxidative stress markers and alteration of the myogenic capacity of satellite cells will be
      compared between three groups. Second, the differential expression of circulating
      proinflammatory molecules will be compared in the serum of the three groups. Identifying
      circulating factors associated with muscle weakness is a necessary step to better understand
      the mechanisms and consider a personalized therapeutic approach that can improve the
      functional and clinical prognosis of disease.

      .
observational model: Other
time perspective: Retrospective
measure: Effects evaluation of circulating pro-inflammatory factors on atrophy
time frame: 6 months
description: Atrophy marker evaluation in cultured muscle cells (myotubes)
cultured myotube diameter exposed to the three serum groups (immunofluorescence)
atrophy (ubiquitin proteasome system, proteolytic autophagy pathway), inflammatory (TNF-alpha, IL-6, IL-8…) and oxidative stress (ROS, lipid peroxidation) markers expressed by cells exposed to the three serum groups (PCR et WesternBlot)
measure: Effects evaluation of circulating pro-inflammatory factors on the myogenic capacities of muscle cells
time frame: 6 months
description: Myogenic capacities of cultured muscle cells (myoblastes)
inflammatory (TNF-alpha, IL-6, IL-8…) and oxidative stress (ROS, lipid peroxidation) markers expressed by cells exposed to the three serum groups (PCR et WesternBlot)
regeneration markers (Notch and myogenesis signaling pathways) expressed by cells exposed to the three serum groups (PCR et WesternBlot)
measure: Identification of one (or more) circulating biomarker (s)
time frame: 3 months
description: Identification of one (or more) circulating biomarker (s) that may be responsible for the muscle alteration induced by the microenvironment of patient in exacerbation of COPD
arm group label: Healthy subject
description: Healthy subject
arm group label: Stable COPD patients
description: Stable COPD patients
arm group label: Exacerbation COPD patients
description: Exacerbation COPD patients
serum
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Maurice HAYOT, MD, PhD
role: Study Director
affiliation: University Hospital, Montpellier
facility: 
country: France
citation: Spruit MA, Gosselink R, Troosters T, Kasran A, Gayan-Ramirez G, Bogaerts P, Bouillon R, Decramer M. Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I. Thorax. 2003 Sep;58(9):752-6. doi: 10.1136/thorax.58.9.752.
PMID: 12947130
citation: Crul T, Testelmans D, Spruit MA, Troosters T, Gosselink R, Geeraerts I, Decramer M, Gayan-Ramirez G. Gene expression profiling in vastus lateralis muscle during an acute exacerbation of COPD. Cell Physiol Biochem. 2010;25(4-5):491-500. doi: 10.1159/000303054. Epub 2010 Mar 23.
PMID: 20332630
citation: Crul T, Spruit MA, Gayan-Ramirez G, Quarck R, Gosselink R, Troosters T, Pitta F, Decramer M. Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients. Eur J Clin Invest. 2007 Nov;37(11):897-904. doi: 10.1111/j.1365-2362.2007.01867.x. Epub 2007 Sep 20.
PMID: 17883420
citation: Catteau M, Gouzi F, Blervaque L, Passerieux E, Blaquiere M, Ayoub B, Bughin F, Mercier J, Hayot M, Pomies P. Effects of a human microenvironment on the differentiation of human myoblasts. Biochem Biophys Res Commun. 2020 May 14;525(4):968-973. doi: 10.1016/j.bbrc.2020.03.020. Epub 2020 Mar 12.
PMID: 32173533
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Muscular Atrophy
mesh term: Atrophy
sharing ipd: Undecided
ipd description: NC