<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/NCT03014609</url>
  </required_header>
  <id_info>
    <org_study_id>38RC16.245</org_study_id>
    <nct_id>NCT03014609</nct_id>
  </id_info>
  <brief_title>Cardiovascular Risk and Chronic Obstructive Pulmonary Disease</brief_title>
  <acronym>ECO-COPD</acronym>
  <official_title>Cardiovascular Risk and Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Grenoble</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Grenoble</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The principal objective of the study is to measure parameters of inflammation, oxidative&#xD;
      stress, and vascular, respiratory, and peripheral muscle function parameters, and identify&#xD;
      parameters indicative of evolving cardiovascular risk (CVR) in COPD patients, using&#xD;
      multivariate analysis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Reduced lung function is a major risk factor for cardiovascular mortality (CV), regardless of&#xD;
      age, sex and history of smoking. Similarly, CV events are known causes of mortality in&#xD;
      patients with chronic obstructive pulmonary disease (COPD). The investigators propose to&#xD;
      determine the parameters influencing the evolution of CV risk in a cohort of COPD patients&#xD;
      followed over 5 years. For this the investigators will study the role of inflammation,&#xD;
      oxidative stress, and vascular, respiratory and peripheral muscle function parameters.&#xD;
&#xD;
      In order to study a sufficient number of patients the investigators propose to group data&#xD;
      from two cohorts: a first cohort of 121 COPD patients that already exists (currently closed&#xD;
      to inclusions but still undergoing follow-up (NCT00404430)) and a new cohort of 150,&#xD;
      decompensated or not, COPD patients.&#xD;
&#xD;
      This study is of major scientific interest and will enable to obtain extremely important&#xD;
      information to better understand COPD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 9, 2017</start_date>
  <completion_date type="Anticipated">December 2029</completion_date>
  <primary_completion_date type="Anticipated">November 2029</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>Change of the pulse wave velocity (PWV)</measure>
    <time_frame>During 5 years since inclusion (once a year)</time_frame>
    <description>Measurement of pulse wave velocity (PWV), which reflects cardiovascular risk (CVR).&#xD;
This measure will be performed at each visit (V1, V1 bis, V2, V3, V4, V5 and V6).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Monitoring of COPD exacerbations compared to evolution of PWV</measure>
    <time_frame>During 5 years since inclusion</time_frame>
    <description>Determination of the relationship between exacerbations and the evolution of the PWV.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relationship between the new cardiovascular (CV) events and the evolution of the PWV.</measure>
    <time_frame>During 5 years since inclusion (once a year)</time_frame>
    <description>Follow-up of exacerbations compared to new CV events (including myocardial infarction with or without ST segment elevation, ischemic stroke, unexplained sudden death at 5 years).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlations between the parameters of severity of pulmonary disease and physical activity.</measure>
    <time_frame>During 5 years since inclusion (once a year)</time_frame>
    <description>Measurement of extent of pulmonary disease; exploration of peripheral muscle function; measurement of physical activity; measurements of endothelial function; measurement of cardiac function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of nocturnal &quot;non-dipping&quot; of blood pressure during COPD.</measure>
    <time_frame>During 5 years since inclusion (once a year)</time_frame>
    <description>Measurement of ambulatory arterial blood pressure during 24 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of sleep disorders and sleep apnea syndrome on the evolution of CVR during COPD.</measure>
    <time_frame>At inclusion visit</time_frame>
    <description>Measurement of sleep disorders and Sleep Apnea Syndrome</description>
  </secondary_outcome>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum and plasma samples will be collected for each patient at the inclusion visit and&#xD;
      follow-up visits. Parameters of inflammation, cardiovascular risk, oxidative stress and&#xD;
      metabolic function will be measured.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        COPD Patients will be recruited during the consultations in Pneumology Department or in the&#xD;
        Laboratory of Sleep (patients with stable COPD) or during their hospitalization in Medical&#xD;
        Reanimation Unit (patients with decompensated COPD) at the University Grenoble Hospital.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For patients with stable COPD:&#xD;
&#xD;
          -  Men or women aged 18 to 85&#xD;
&#xD;
          -  FEV1/FVC &lt; 70% or proven BPCO&#xD;
&#xD;
          -  Patients who have given their free and informed consent in writing&#xD;
&#xD;
        For patients with decompensated COPD:&#xD;
&#xD;
          -  Men or women aged 18 to 85&#xD;
&#xD;
          -  FEV1/FVC &lt; 70% or proven BPCO&#xD;
&#xD;
          -  At the time of acute respiratory failure (ARF), when admitted to hospital:&#xD;
&#xD;
               -  Respiratory rate &gt; 25 cycles per minute&#xD;
&#xD;
               -  PaCO2 &gt; 45 mmHg&#xD;
&#xD;
               -  blood pH &lt; 7.35&#xD;
&#xD;
          -  When included in the study:&#xD;
&#xD;
               -  pH &gt; 7.33 at the end of ARF, 2 days in a row, or 3 to 7 days post-D1&#xD;
                  decompensation (admission to the hospital)&#xD;
&#xD;
               -  Fever &lt; 38.5°C&#xD;
&#xD;
          -  Patients who have given their free and informed consent in writing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Obvious evolving infection or CRP &gt; 100 mg/L&#xD;
&#xD;
          -  Cardiac decompensation considered the main cause of decompensation or chronic heart&#xD;
             failure with LVEF &lt; 45%&#xD;
&#xD;
          -  Evolving neoplasia&#xD;
&#xD;
          -  On antioxidants: N-acetyl-cysteine, selenium, vit. C, vit. E&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Patients under tutorship or curatorship&#xD;
&#xD;
          -  Patients participating in a drug clinical research study&#xD;
&#xD;
          -  Patients not affiliated to the French social security system (or equivalent)&#xD;
&#xD;
          -  Patients deprived of liberty or hospitalized without consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jean-Louis PEPIN, ProfessorPHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Grenoble Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jean-Louis PEPIN, ProfessorPHD</last_name>
    <phone>+33 476 768 473</phone>
    <email>JPepin@chu-grenoble.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sandrine BOUZON, CRA</last_name>
    <phone>+33 476 767 244</phone>
    <email>SBouzon@chu-grenoble.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Grenoble Hospital</name>
      <address>
        <city>Grenoble</city>
        <state>La Tronche</state>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jean-Louis PEPIN, ProfessorPhD</last_name>
      <phone>+33 476 768 473</phone>
      <email>JPepin@chu-grenoble.fr</email>
    </contact>
    <contact_backup>
      <last_name>Sandrine BOUZON, CRA</last_name>
      <phone>+33 476 767 244</phone>
      <email>SBouzon@chu-grenoble.fr</email>
    </contact_backup>
    <investigator>
      <last_name>Renaud TAMISIER, ProfessorPhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patrick LEVY, ProfessorPhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Cécile BOSC, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Marie DESTORS, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sam BAYAT, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stéphane DOUTRELEAU, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bernard WUYAM, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>François ARBIB, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Damien VIGLINO, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicolas TERZI, ProfessorPhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gilles BARONE-ROCHETTE, ProfessorPhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Patrice FAURE, ProfessorPhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Gilbert FERRETTI, ProfessorPhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <results_reference>
    <citation>Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004 Jul;59(7):574-80. doi: 10.1136/thx.2003.019588.</citation>
    <PMID>15223864</PMID>
  </results_reference>
  <results_reference>
    <citation>Mallia P, Johnston SL. Mechanisms and experimental models of chronic obstructive pulmonary disease exacerbations. Proc Am Thorac Soc. 2005;2(4):361-6; discussion 371-2. doi: 10.1513/pats.200504-025SR.</citation>
    <PMID>16267363</PMID>
  </results_reference>
  <results_reference>
    <citation>de Torres JP, Cordoba-Lanus E, Lopez-Aguilar C, Muros de Fuentes M, Montejo de Garcini A, Aguirre-Jaime A, Celli BR, Casanova C. C-reactive protein levels and clinically important predictive outcomes in stable COPD patients. Eur Respir J. 2006 May;27(5):902-7. doi: 10.1183/09031936.06.00109605. Epub 2006 Feb 2.</citation>
    <PMID>16455829</PMID>
  </results_reference>
  <results_reference>
    <citation>Malo O, Sauleda J, Busquets X, Miralles C, Agusti AG, Noguera A. [Systemic inflammation during exacerbations of chronic obstructive pulmonary disease]. Arch Bronconeumol. 2002 Apr;38(4):172-6. Spanish.</citation>
    <PMID>11953269</PMID>
  </results_reference>
  <results_reference>
    <citation>Dekhuijzen PN, Aben KK, Dekker I, Aarts LP, Wielders PL, van Herwaarden CL, Bast A. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):813-6. doi: 10.1164/ajrccm.154.3.8810624.</citation>
    <PMID>8810624</PMID>
  </results_reference>
  <results_reference>
    <citation>Rahman I. The role of oxidative stress in the pathogenesis of COPD: implications for therapy. Treat Respir Med. 2005;4(3):175-200. doi: 10.2165/00151829-200504030-00003.</citation>
    <PMID>15987234</PMID>
  </results_reference>
  <results_reference>
    <citation>Heunks LM, Vina J, van Herwaarden CL, Folgering HT, Gimeno A, Dekhuijzen PN. Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease. Am J Physiol. 1999 Dec;277(6):R1697-704. doi: 10.1152/ajpregu.1999.277.6.R1697.</citation>
    <PMID>10600916</PMID>
  </results_reference>
  <results_reference>
    <citation>Yende S, Waterer GW, Tolley EA, Newman AB, Bauer DC, Taaffe DR, Jensen R, Crapo R, Rubin S, Nevitt M, Simonsick EM, Satterfield S, Harris T, Kritchevsky SB. Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax. 2006 Jan;61(1):10-6. doi: 10.1136/thx.2004.034181. Epub 2005 Nov 11.</citation>
    <PMID>16284220</PMID>
  </results_reference>
  <results_reference>
    <citation>Carter R, Holiday DB, Nwasuruba C, Stocks J, Grothues C, Tiep B. 6-minute walk work for assessment of functional capacity in patients with COPD. Chest. 2003 May;123(5):1408-15. doi: 10.1378/chest.123.5.1408.</citation>
    <PMID>12740255</PMID>
  </results_reference>
  <results_reference>
    <citation>Mador MJ, Kufel TJ, Pineda LA, Sharma GK. Diaphragmatic fatigue and high-intensity exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 Jan;161(1):118-23. doi: 10.1164/ajrccm.161.1.9903010.</citation>
    <PMID>10619807</PMID>
  </results_reference>
  <results_reference>
    <citation>Saey D, Debigare R, LeBlanc P, Mador MJ, Cote CH, Jobin J, Maltais F. Contractile leg fatigue after cycle exercise: a factor limiting exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003 Aug 15;168(4):425-30. doi: 10.1164/rccm.200208-856OC. Epub 2003 Apr 24.</citation>
    <PMID>12714348</PMID>
  </results_reference>
  <results_reference>
    <citation>Engelen MP, Schols AM, Does JD, Wouters EF. Skeletal muscle weakness is associated with wasting of extremity fat-free mass but not with airflow obstruction in patients with chronic obstructive pulmonary disease. Am J Clin Nutr. 2000 Mar;71(3):733-8. doi: 10.1093/ajcn/71.3.733.</citation>
    <PMID>10702166</PMID>
  </results_reference>
  <results_reference>
    <citation>Barreiro E, de la Puente B, Minguella J, Corominas JM, Serrano S, Hussain SN, Gea J. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 May 15;171(10):1116-24. doi: 10.1164/rccm.200407-887OC. Epub 2005 Feb 25.</citation>
    <PMID>15735057</PMID>
  </results_reference>
  <results_reference>
    <citation>Debigare R, Cote CH, Maltais F. Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. Am J Respir Crit Care Med. 2001 Nov 1;164(9):1712-7. doi: 10.1164/ajrccm.164.9.2104035. No abstract available.</citation>
    <PMID>11719314</PMID>
  </results_reference>
  <results_reference>
    <citation>Heunks LM, Dekhuijzen PN. Respiratory muscle function and free radicals: from cell to COPD. Thorax. 2000 Aug;55(8):704-16. doi: 10.1136/thorax.55.8.704. No abstract available.</citation>
    <PMID>10899251</PMID>
  </results_reference>
  <results_reference>
    <citation>Hunninghake DB. Cardiovascular disease in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(1):44-9. doi: 10.1513/pats.200410-050SF.</citation>
    <PMID>16113468</PMID>
  </results_reference>
  <results_reference>
    <citation>Rennard SI. Clinical approach to patients with chronic obstructive pulmonary disease and cardiovascular disease. Proc Am Thorac Soc. 2005;2(1):94-100. doi: 10.1513/pats.200410-051SF.</citation>
    <PMID>16113475</PMID>
  </results_reference>
  <results_reference>
    <citation>Gan WQ, Man SF, Sin DD. The interactions between cigarette smoking and reduced lung function on systemic inflammation. Chest. 2005 Feb;127(2):558-64. doi: 10.1378/chest.127.2.558.</citation>
    <PMID>15705996</PMID>
  </results_reference>
  <results_reference>
    <citation>MacCallum PK. Markers of hemostasis and systemic inflammation in heart disease and atherosclerosis in smokers. Proc Am Thorac Soc. 2005;2(1):34-43. doi: 10.1513/pats.200406-036MS.</citation>
    <PMID>16113467</PMID>
  </results_reference>
  <results_reference>
    <citation>Vassilakopoulos T, Karatza MH, Katsaounou P, Kollintza A, Zakynthinos S, Roussos C. Antioxidants attenuate the plasma cytokine response to exercise in humans. J Appl Physiol (1985). 2003 Mar;94(3):1025-32. doi: 10.1152/japplphysiol.00735.2002. Epub 2002 Nov 27.</citation>
    <PMID>12571133</PMID>
  </results_reference>
  <results_reference>
    <citation>Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005 Jan 25;111(3):363-8. doi: 10.1161/01.CIR.0000153339.27064.14. No abstract available.</citation>
    <PMID>15668353</PMID>
  </results_reference>
  <results_reference>
    <citation>Vivodtzev I, Minet C, Wuyam B, Borel JC, Vottero G, Monneret D, Baguet JP, Levy P, Pepin JL. Significant improvement in arterial stiffness after endurance training in patients with COPD. Chest. 2010 Mar;137(3):585-92. doi: 10.1378/chest.09-1437. Epub 2009 Oct 31.</citation>
    <PMID>19880908</PMID>
  </results_reference>
  <results_reference>
    <citation>Minet C, Vivodtzev I, Tamisier R, Arbib F, Wuyam B, Timsit JF, Monneret D, Borel JC, Baguet JP, Levy P, Pepin JL. Reduced six-minute walking distance, high fat-free-mass index and hypercapnia are associated with endothelial dysfunction in COPD. Respir Physiol Neurobiol. 2012 Aug 15;183(2):128-34. doi: 10.1016/j.resp.2012.06.017. Epub 2012 Jun 18.</citation>
    <PMID>22721944</PMID>
  </results_reference>
  <results_reference>
    <citation>Vivodtzev I, Tamisier R, Baguet JP, Borel JC, Levy P, Pepin JL. Arterial stiffness in COPD. Chest. 2014 Apr;145(4):861-875. doi: 10.1378/chest.13-1809.</citation>
    <PMID>24687708</PMID>
  </results_reference>
  <results_reference>
    <citation>Weidemann F, Herrmann S, Stork S, Niemann M, Frantz S, Lange V, Beer M, Gattenlohner S, Voelker W, Ertl G, Strotmann JM. Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis. Circulation. 2009 Aug 18;120(7):577-84. doi: 10.1161/CIRCULATIONAHA.108.847772. Epub 2009 Aug 3.</citation>
    <PMID>19652094</PMID>
  </results_reference>
  <results_reference>
    <citation>Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010 Aug 1;182(3):325-31. doi: 10.1164/rccm.200912-1869OC. Epub 2010 Apr 8.</citation>
    <PMID>20378728</PMID>
  </results_reference>
  <results_reference>
    <citation>Vivodtzev I, Minet C, Tamisier R, Arbib F, Borel JC, Baguet JP, Levy P, Pepin JL. Arterial stiffness by pulse wave velocity in COPD: reliability and reproducibility. Eur Respir J. 2013 Oct;42(4):1140-2. doi: 10.1183/09031936.00014813. No abstract available.</citation>
    <PMID>24081763</PMID>
  </results_reference>
  <results_reference>
    <citation>Patel AR, Kowlessar BS, Donaldson GC, Mackay AJ, Singh R, George SN, Garcha DS, Wedzicha JA, Hurst JR. Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013 Nov 1;188(9):1091-9. doi: 10.1164/rccm.201306-1170OC.</citation>
    <PMID>24033321</PMID>
  </results_reference>
  <results_reference>
    <citation>Labarere J, Renaud B, Fine MJ. How to derive and validate clinical prediction models for use in intensive care medicine. Intensive Care Med. 2014 Apr;40(4):513-27. doi: 10.1007/s00134-014-3227-6. Epub 2014 Feb 26. Erratum In: Intensive Care Med. 2014 Jun;40(6):925. Bertrand, Renaud [corrected to Renaud, Bertrand].</citation>
    <PMID>24570265</PMID>
  </results_reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 9, 2017</study_first_posted>
  <last_update_submitted>May 22, 2023</last_update_submitted>
  <last_update_submitted_qc>May 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic obstructive pulmonary disease</keyword>
  <keyword>cardiovascular risk</keyword>
  <keyword>inflammation</keyword>
  <keyword>oxidative stress</keyword>
  <keyword>peripheral muscle function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</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/NCT03014609
org study id: 38RC16.245
nct id: NCT03014609
lead sponsor: 
has dmc: Yes
The principal objective of the study is to measure parameters of inflammation, oxidative
      stress, and vascular, respiratory, and peripheral muscle function parameters, and identify
      parameters indicative of evolving cardiovascular risk (CVR) in COPD patients, using
      multivariate analysis.
Reduced lung function is a major risk factor for cardiovascular mortality (CV), regardless of
      age, sex and history of smoking. Similarly, CV events are known causes of mortality in
      patients with chronic obstructive pulmonary disease (COPD). The investigators propose to
      determine the parameters influencing the evolution of CV risk in a cohort of COPD patients
      followed over 5 years. For this the investigators will study the role of inflammation,
      oxidative stress, and vascular, respiratory and peripheral muscle function parameters.

      In order to study a sufficient number of patients the investigators propose to group data
      from two cohorts: a first cohort of 121 COPD patients that already exists (currently closed
      to inclusions but still undergoing follow-up (NCT00404430)) and a new cohort of 150,
      decompensated or not, COPD patients.

      This study is of major scientific interest and will enable to obtain extremely important
      information to better understand COPD.
observational model: Cohort
time perspective: Prospective
measure: Change of the pulse wave velocity (PWV)
time frame: During 5 years since inclusion (once a year)
description: Measurement of pulse wave velocity (PWV), which reflects cardiovascular risk (CVR).
This measure will be performed at each visit (V1, V1 bis, V2, V3, V4, V5 and V6).
measure: Monitoring of COPD exacerbations compared to evolution of PWV
time frame: During 5 years since inclusion
description: Determination of the relationship between exacerbations and the evolution of the PWV.
measure: Relationship between the new cardiovascular (CV) events and the evolution of the PWV.
time frame: During 5 years since inclusion (once a year)
description: Follow-up of exacerbations compared to new CV events (including myocardial infarction with or without ST segment elevation, ischemic stroke, unexplained sudden death at 5 years).
measure: Correlations between the parameters of severity of pulmonary disease and physical activity.
time frame: During 5 years since inclusion (once a year)
description: Measurement of extent of pulmonary disease; exploration of peripheral muscle function; measurement of physical activity; measurements of endothelial function; measurement of cardiac function.
measure: Prevalence of nocturnal "non-dipping" of blood pressure during COPD.
time frame: During 5 years since inclusion (once a year)
description: Measurement of ambulatory arterial blood pressure during 24 hours
measure: Impact of sleep disorders and sleep apnea syndrome on the evolution of CVR during COPD.
time frame: At inclusion visit
description: Measurement of sleep disorders and Sleep Apnea Syndrome
Serum and plasma samples will be collected for each patient at the inclusion visit and
      follow-up visits. Parameters of inflammation, cardiovascular risk, oxidative stress and
      metabolic function will be measured.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Jean-Louis PEPIN, ProfessorPHD
role: Principal Investigator
affiliation: University Grenoble Hospital
last name: Jean-Louis PEPIN, ProfessorPHD
phone: +33 476 768 473
email: JPepin@chu-grenoble.fr
last name: Sandrine BOUZON, CRA
phone: +33 476 767 244
email: SBouzon@chu-grenoble.fr
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: France
citation: Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004 Jul;59(7):574-80. doi: 10.1136/thx.2003.019588.
PMID: 15223864
citation: Mallia P, Johnston SL. Mechanisms and experimental models of chronic obstructive pulmonary disease exacerbations. Proc Am Thorac Soc. 2005;2(4):361-6; discussion 371-2. doi: 10.1513/pats.200504-025SR.
PMID: 16267363
citation: de Torres JP, Cordoba-Lanus E, Lopez-Aguilar C, Muros de Fuentes M, Montejo de Garcini A, Aguirre-Jaime A, Celli BR, Casanova C. C-reactive protein levels and clinically important predictive outcomes in stable COPD patients. Eur Respir J. 2006 May;27(5):902-7. doi: 10.1183/09031936.06.00109605. Epub 2006 Feb 2.
PMID: 16455829
citation: Malo O, Sauleda J, Busquets X, Miralles C, Agusti AG, Noguera A. [Systemic inflammation during exacerbations of chronic obstructive pulmonary disease]. Arch Bronconeumol. 2002 Apr;38(4):172-6. Spanish.
PMID: 11953269
citation: Dekhuijzen PN, Aben KK, Dekker I, Aarts LP, Wielders PL, van Herwaarden CL, Bast A. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):813-6. doi: 10.1164/ajrccm.154.3.8810624.
PMID: 8810624
citation: Rahman I. The role of oxidative stress in the pathogenesis of COPD: implications for therapy. Treat Respir Med. 2005;4(3):175-200. doi: 10.2165/00151829-200504030-00003.
PMID: 15987234
citation: Heunks LM, Vina J, van Herwaarden CL, Folgering HT, Gimeno A, Dekhuijzen PN. Xanthine oxidase is involved in exercise-induced oxidative stress in chronic obstructive pulmonary disease. Am J Physiol. 1999 Dec;277(6):R1697-704. doi: 10.1152/ajpregu.1999.277.6.R1697.
PMID: 10600916
citation: Yende S, Waterer GW, Tolley EA, Newman AB, Bauer DC, Taaffe DR, Jensen R, Crapo R, Rubin S, Nevitt M, Simonsick EM, Satterfield S, Harris T, Kritchevsky SB. Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects. Thorax. 2006 Jan;61(1):10-6. doi: 10.1136/thx.2004.034181. Epub 2005 Nov 11.
PMID: 16284220
citation: Carter R, Holiday DB, Nwasuruba C, Stocks J, Grothues C, Tiep B. 6-minute walk work for assessment of functional capacity in patients with COPD. Chest. 2003 May;123(5):1408-15. doi: 10.1378/chest.123.5.1408.
PMID: 12740255
citation: Mador MJ, Kufel TJ, Pineda LA, Sharma GK. Diaphragmatic fatigue and high-intensity exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000 Jan;161(1):118-23. doi: 10.1164/ajrccm.161.1.9903010.
PMID: 10619807
citation: Saey D, Debigare R, LeBlanc P, Mador MJ, Cote CH, Jobin J, Maltais F. Contractile leg fatigue after cycle exercise: a factor limiting exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003 Aug 15;168(4):425-30. doi: 10.1164/rccm.200208-856OC. Epub 2003 Apr 24.
PMID: 12714348
citation: Engelen MP, Schols AM, Does JD, Wouters EF. Skeletal muscle weakness is associated with wasting of extremity fat-free mass but not with airflow obstruction in patients with chronic obstructive pulmonary disease. Am J Clin Nutr. 2000 Mar;71(3):733-8. doi: 10.1093/ajcn/71.3.733.
PMID: 10702166
citation: Barreiro E, de la Puente B, Minguella J, Corominas JM, Serrano S, Hussain SN, Gea J. Oxidative stress and respiratory muscle dysfunction in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 May 15;171(10):1116-24. doi: 10.1164/rccm.200407-887OC. Epub 2005 Feb 25.
PMID: 15735057
citation: Debigare R, Cote CH, Maltais F. Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. Am J Respir Crit Care Med. 2001 Nov 1;164(9):1712-7. doi: 10.1164/ajrccm.164.9.2104035. No abstract available.
PMID: 11719314
citation: Heunks LM, Dekhuijzen PN. Respiratory muscle function and free radicals: from cell to COPD. Thorax. 2000 Aug;55(8):704-16. doi: 10.1136/thorax.55.8.704. No abstract available.
PMID: 10899251
citation: Hunninghake DB. Cardiovascular disease in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(1):44-9. doi: 10.1513/pats.200410-050SF.
PMID: 16113468
citation: Rennard SI. Clinical approach to patients with chronic obstructive pulmonary disease and cardiovascular disease. Proc Am Thorac Soc. 2005;2(1):94-100. doi: 10.1513/pats.200410-051SF.
PMID: 16113475
citation: Gan WQ, Man SF, Sin DD. The interactions between cigarette smoking and reduced lung function on systemic inflammation. Chest. 2005 Feb;127(2):558-64. doi: 10.1378/chest.127.2.558.
PMID: 15705996
citation: MacCallum PK. Markers of hemostasis and systemic inflammation in heart disease and atherosclerosis in smokers. Proc Am Thorac Soc. 2005;2(1):34-43. doi: 10.1513/pats.200406-036MS.
PMID: 16113467
citation: Vassilakopoulos T, Karatza MH, Katsaounou P, Kollintza A, Zakynthinos S, Roussos C. Antioxidants attenuate the plasma cytokine response to exercise in humans. J Appl Physiol (1985). 2003 Mar;94(3):1025-32. doi: 10.1152/japplphysiol.00735.2002. Epub 2002 Nov 27.
PMID: 12571133
citation: Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005 Jan 25;111(3):363-8. doi: 10.1161/01.CIR.0000153339.27064.14. No abstract available.
PMID: 15668353
citation: Vivodtzev I, Minet C, Wuyam B, Borel JC, Vottero G, Monneret D, Baguet JP, Levy P, Pepin JL. Significant improvement in arterial stiffness after endurance training in patients with COPD. Chest. 2010 Mar;137(3):585-92. doi: 10.1378/chest.09-1437. Epub 2009 Oct 31.
PMID: 19880908
citation: Minet C, Vivodtzev I, Tamisier R, Arbib F, Wuyam B, Timsit JF, Monneret D, Borel JC, Baguet JP, Levy P, Pepin JL. Reduced six-minute walking distance, high fat-free-mass index and hypercapnia are associated with endothelial dysfunction in COPD. Respir Physiol Neurobiol. 2012 Aug 15;183(2):128-34. doi: 10.1016/j.resp.2012.06.017. Epub 2012 Jun 18.
PMID: 22721944
citation: Vivodtzev I, Tamisier R, Baguet JP, Borel JC, Levy P, Pepin JL. Arterial stiffness in COPD. Chest. 2014 Apr;145(4):861-875. doi: 10.1378/chest.13-1809.
PMID: 24687708
citation: Weidemann F, Herrmann S, Stork S, Niemann M, Frantz S, Lange V, Beer M, Gattenlohner S, Voelker W, Ertl G, Strotmann JM. Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis. Circulation. 2009 Aug 18;120(7):577-84. doi: 10.1161/CIRCULATIONAHA.108.847772. Epub 2009 Aug 3.
PMID: 19652094
citation: Marin JM, Soriano JB, Carrizo SJ, Boldova A, Celli BR. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med. 2010 Aug 1;182(3):325-31. doi: 10.1164/rccm.200912-1869OC. Epub 2010 Apr 8.
PMID: 20378728
citation: Vivodtzev I, Minet C, Tamisier R, Arbib F, Borel JC, Baguet JP, Levy P, Pepin JL. Arterial stiffness by pulse wave velocity in COPD: reliability and reproducibility. Eur Respir J. 2013 Oct;42(4):1140-2. doi: 10.1183/09031936.00014813. No abstract available.
PMID: 24081763
citation: Patel AR, Kowlessar BS, Donaldson GC, Mackay AJ, Singh R, George SN, Garcha DS, Wedzicha JA, Hurst JR. Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013 Nov 1;188(9):1091-9. doi: 10.1164/rccm.201306-1170OC.
PMID: 24033321
citation: Labarere J, Renaud B, Fine MJ. How to derive and validate clinical prediction models for use in intensive care medicine. Intensive Care Med. 2014 Apr;40(4):513-27. doi: 10.1007/s00134-014-3227-6. Epub 2014 Feb 26. Erratum In: Intensive Care Med. 2014 Jun;40(6):925. Bertrand, Renaud [corrected to Renaud, Bertrand].
PMID: 24570265
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive