<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/NCT03285100</url>
  </required_header>
  <id_info>
    <org_study_id>NL60536.091.17</org_study_id>
    <nct_id>NCT03285100</nct_id>
  </id_info>
  <brief_title>The Effects of Discontinuation of Vitamin K Antagonists on the Rate of Elastin Degradation</brief_title>
  <official_title>Pilot Study to Assess the Effects of Discontinuation of Vitamin K Antagonists on the Rate of Elastin Degradation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Canisius-Wilhelmina Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Canisius-Wilhelmina 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>
      Background: Elastin is a unique protein providing elasticity, resilience and deformability to&#xD;
      dynamic tissues, such as lungs and vasculature. Elastin fibers are characterized by their&#xD;
      high affinity for calcium. However, calcified elastin is more prone to the degrading effects&#xD;
      of proteases and, in turn, partially degraded elastin has an even higher affinity for&#xD;
      calcium. A disturbed balance between proteases and anti-proteases is a major underlying&#xD;
      mechanism in the development of chronic obstructive pulmonary disease (COPD). Virtually the&#xD;
      only protein that can protect elastin from calcification is matrix Gla-protein (MGP), which&#xD;
      needs vitamin K for its activation. In COPD patients, a lower vitamin K status is found when&#xD;
      compared to control subjects and an inverse association exists between vitamin K status and&#xD;
      elastin degradation. In addition, vitamin K status is lower and elastin degradation is&#xD;
      accelerated in Vitamin K antagonist (VKA) users.&#xD;
&#xD;
      VKAs are widely used. Nowadays, an increasing number of patients uses direct oral&#xD;
      anticoagulants (DOACs), which do not influence vitamin K status. The hypothesis of this study&#xD;
      is that discontinuation of VKAs results in an improved vitamin K status and deceleration of&#xD;
      elastin degradation. In order to test this hypothesis, an observational pilot study will be&#xD;
      conducted in which the change in elastin degradation- quantified by plasma desmosine&#xD;
      concentrations - in patients who discontinue use of VKAs will be used as primary endpoint.&#xD;
&#xD;
      Study design: Observational study. Study population: A total of 30 VKA users who will&#xD;
      discontinue the use of VKAs. Elastin degradation rate (quantified by plasma desmosine levels)&#xD;
      and vitamin K status (quantified by measuring plasma levels of dephosphorylated&#xD;
      uncarboxylated (dp-uc)MGP) will be measured during the use of VKAs and approximately 6 months&#xD;
      after discontinuation of VKAs. Furthermore, the VKORC1 polymorphisms will be determined.&#xD;
&#xD;
      Main study parameters: The primary endpoint is the change in the rate of elastin degradation&#xD;
      quantified by the plasma desmosine assay. Secondary endpoints are the change in vitamin K&#xD;
      status quantified by measuring plasma levels of dp-ucMGP, the relation between desmosine and&#xD;
      dp-ucMGP and differences of desmosine and dp-ucMGP levels among subjects with different&#xD;
      polymorphisms of the vitamin K 2,3-epoxide reductase complex 1 (VKORC1) gene.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 31, 2017</start_date>
  <completion_date type="Anticipated">October 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2018</primary_completion_date>
  <study_type>Observational</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>
  <primary_outcome>
    <measure>Difference in elastin degradation rate</measure>
    <time_frame>Plasma desmosine is measured at baseline and 6 months after discontinuation of VKAs</time_frame>
    <description>Difference in elastin degradation rate before and after discontinuation of VKAs, quantified by the change in plasma desmosine levels</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in vitamin K status</measure>
    <time_frame>Plasma dp-ucMGP is measured at baseline and 6 months after discontinuation of VKAs</time_frame>
    <description>Difference in vitamin K status before and after discontinuation of VKAs, quantified by the change in dp-ucMGP, discontinuation of VKAs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Association between desmosine and dp-ucMGP</measure>
    <time_frame>Desmosine and dp-ucMGP are determined before discontinuation of VKAs and 6 months after discontinuation of VKAs</time_frame>
    <description>Association between desmosine and dp-ucMGP both in patients who use VKAs and do not use VKAs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differences in desmosine and dp-ucMGP levels between different VKORC1 polymorphisms</measure>
    <time_frame>Desmosine and dp-ucMGP are determined, both before discontinuation of VKAs and 6 months after discontinuation of VKAs. VKORC1 polymorphisms are determined before discontinuation of VKAs.</time_frame>
    <description>Levels of dp-ucMGP and desmosine levels of subjects with different VKORC1 polymorphisms are compared, both during the use of VKAs and after discontinuation.</description>
  </secondary_outcome>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Emphysema or COPD</condition>
  <condition>Aneurysm</condition>
  <condition>Cystic Fibrosis</condition>
  <condition>Alpha 1-Antitrypsin Deficiency</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Venipuncture</intervention_name>
    <description>Approximately 6 months after discontinuation of VKAs one additional venipuncture will be performed for determination of dp-ucMGP and desmosine.&#xD;
At baseline two additional blood collection tubes will be drawn for determination of dp-ucMGP, desmosine and VKORC1 polymorphisms. Since this is during one of the last regular International Normalized Ratio (INR) testing at the anticoagulation clinic, no additional venipuncture has to be performed at this moment.</description>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      -  at baseline: blood sample of 15mL (EDTA-plasma), divided in four two portions (one for&#xD;
           determination of dp-ucMGP and one for desmosine)&#xD;
&#xD;
        -  at baseline: blood sample of 10mL (EDTA-plasma). DNA will be isolated from these samples&#xD;
           for determination of the VKORC1 polymorphisms&#xD;
&#xD;
        -  after six months: blood sample of 15mL (EDTA-plasma), divided in four two portions (one&#xD;
           for determination of dp-ucMGP and one for desmosine)&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        30 VKA users from the anticoagulant clinic in the Canisius Wilhelmina Hospital, who are&#xD;
        going to discontinue the use of VKAs at short time&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Use of VKAs for at least 3 months&#xD;
&#xD;
          -  Stop VKAs at short time&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Ability to comply with all study requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active malignancy or cured malignancy &lt;12 months prior to enrollment&#xD;
&#xD;
          -  Use of maintenance dose oral corticosteroids&#xD;
&#xD;
          -  Serious mental impairment&#xD;
&#xD;
          -  Life expectation of less than 6 months on the basis of concurrent disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rob Janssen, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Canisius-Wilhelmina Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rob Janssen, MD, PhD</last_name>
    <phone>+31-24-3658755</phone>
    <email>rob.janssen@cwz.nl</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ianthe Piscaer, MD</last_name>
    <phone>+31-43-3875051</phone>
    <email>ianthe.piscaer@mumc.nl</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Canisius Wilhelmina Hospital</name>
      <address>
        <city>Nijmegen</city>
        <zip>6532SZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rob Janssen, MD, PhD</last_name>
      <phone>+31-24-3658755</phone>
      <email>rob.janssen@cwz.nl</email>
    </contact>
    <investigator>
      <last_name>Rob Janssen, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ianthe Piscaer, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ruben Zaal, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Mithieux SM, Weiss AS. Elastin. Adv Protein Chem. 2005;70:437-61. doi: 10.1016/S0065-3233(05)70013-9.</citation>
    <PMID>15837523</PMID>
  </reference>
  <reference>
    <citation>Robert L, Robert AM, Fulop T. Rapid increase in human life expectancy: will it soon be limited by the aging of elastin? Biogerontology. 2008 Apr;9(2):119-33. doi: 10.1007/s10522-007-9122-6. Epub 2008 Jan 4.</citation>
    <PMID>18175202</PMID>
  </reference>
  <reference>
    <citation>Bouvet C, Moreau S, Blanchette J, de Blois D, Moreau P. Sequential activation of matrix metalloproteinase 9 and transforming growth factor beta in arterial elastocalcinosis. Arterioscler Thromb Vasc Biol. 2008 May;28(5):856-62. doi: 10.1161/ATVBAHA.107.153056. Epub 2008 Feb 21.</citation>
    <PMID>18292396</PMID>
  </reference>
  <reference>
    <citation>Basalyga DM, Simionescu DT, Xiong W, Baxter BT, Starcher BC, Vyavahare NR. Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases. Circulation. 2004 Nov 30;110(22):3480-7. doi: 10.1161/01.CIR.0000148367.08413.E9. Epub 2004 Nov 15.</citation>
    <PMID>15545515</PMID>
  </reference>
  <reference>
    <citation>Turino GM, Ma S, Lin YY, Cantor JO, Luisetti M. Matrix elastin: a promising biomarker for chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011 Sep 15;184(6):637-41. doi: 10.1164/rccm.201103-0450PP.</citation>
    <PMID>21757624</PMID>
  </reference>
  <reference>
    <citation>Maclay JD, McAllister DA, Rabinovich R, Haq I, Maxwell S, Hartland S, Connell M, Murchison JT, van Beek EJ, Gray RD, Mills NL, Macnee W. Systemic elastin degradation in chronic obstructive pulmonary disease. Thorax. 2012 Jul;67(7):606-12. doi: 10.1136/thoraxjnl-2011-200949. Epub 2012 Feb 28.</citation>
    <PMID>22374923</PMID>
  </reference>
  <reference>
    <citation>Williams MC, Murchison JT, Edwards LD, Agusti A, Bakke P, Calverley PM, Celli B, Coxson HO, Crim C, Lomas DA, Miller BE, Rennard S, Silverman EK, Tal-Singer R, Vestbo J, Wouters E, Yates JC, van Beek EJ, Newby DE, MacNee W; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Coronary artery calcification is increased in patients with COPD and associated with increased morbidity and mortality. Thorax. 2014 Aug;69(8):718-23. doi: 10.1136/thoraxjnl-2012-203151. Epub 2014 Jan 28.</citation>
    <PMID>24473329</PMID>
  </reference>
  <reference>
    <citation>Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5. doi: 10.1093/jn/134.11.3100.</citation>
    <PMID>15514282</PMID>
  </reference>
  <reference>
    <citation>Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb 19.</citation>
    <PMID>25694037</PMID>
  </reference>
  <reference>
    <citation>Patillon B, Luisi P, Blanche H, Patin E, Cann HM, Genin E, Sabbagh A. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans. PLoS One. 2012;7(12):e53049. doi: 10.1371/journal.pone.0053049. Epub 2012 Dec 28.</citation>
    <PMID>23285254</PMID>
  </reference>
  <reference>
    <citation>Rabinovich RA, Miller BE, Wrobel K, Ranjit K, Williams MC, Drost E, Edwards LD, Lomas DA, Rennard SI, Agusti A, Tal-Singer R, Vestbo J, Wouters EF, John M, van Beek EJ, Murchison JT, Bolton CE, MacNee W, Huang JT; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD. Eur Respir J. 2016 May;47(5):1365-73. doi: 10.1183/13993003.01824-2015. Epub 2016 Mar 23.</citation>
    <PMID>27009168</PMID>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>January 23, 2018</last_update_submitted>
  <last_update_submitted_qc>January 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Canisius-Wilhelmina Hospital</investigator_affiliation>
    <investigator_full_name>Rob Janssen</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Alpha 1-Antitrypsin Deficiency</mesh_term>
    <mesh_term>Aneurysm</mesh_term>
    <mesh_term>Emphysema</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT03285100/ICF_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 21, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT03285100/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03285100
org study id: NL60536.091.17
nct id: NCT03285100
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background: Elastin is a unique protein providing elasticity, resilience and deformability to
      dynamic tissues, such as lungs and vasculature. Elastin fibers are characterized by their
      high affinity for calcium. However, calcified elastin is more prone to the degrading effects
      of proteases and, in turn, partially degraded elastin has an even higher affinity for
      calcium. A disturbed balance between proteases and anti-proteases is a major underlying
      mechanism in the development of chronic obstructive pulmonary disease (COPD). Virtually the
      only protein that can protect elastin from calcification is matrix Gla-protein (MGP), which
      needs vitamin K for its activation. In COPD patients, a lower vitamin K status is found when
      compared to control subjects and an inverse association exists between vitamin K status and
      elastin degradation. In addition, vitamin K status is lower and elastin degradation is
      accelerated in Vitamin K antagonist (VKA) users.

      VKAs are widely used. Nowadays, an increasing number of patients uses direct oral
      anticoagulants (DOACs), which do not influence vitamin K status. The hypothesis of this study
      is that discontinuation of VKAs results in an improved vitamin K status and deceleration of
      elastin degradation. In order to test this hypothesis, an observational pilot study will be
      conducted in which the change in elastin degradation- quantified by plasma desmosine
      concentrations - in patients who discontinue use of VKAs will be used as primary endpoint.

      Study design: Observational study. Study population: A total of 30 VKA users who will
      discontinue the use of VKAs. Elastin degradation rate (quantified by plasma desmosine levels)
      and vitamin K status (quantified by measuring plasma levels of dephosphorylated
      uncarboxylated (dp-uc)MGP) will be measured during the use of VKAs and approximately 6 months
      after discontinuation of VKAs. Furthermore, the VKORC1 polymorphisms will be determined.

      Main study parameters: The primary endpoint is the change in the rate of elastin degradation
      quantified by the plasma desmosine assay. Secondary endpoints are the change in vitamin K
      status quantified by measuring plasma levels of dp-ucMGP, the relation between desmosine and
      dp-ucMGP and differences of desmosine and dp-ucMGP levels among subjects with different
      polymorphisms of the vitamin K 2,3-epoxide reductase complex 1 (VKORC1) gene.
observational model: Cohort
time perspective: Prospective
measure: Difference in elastin degradation rate
time frame: Plasma desmosine is measured at baseline and 6 months after discontinuation of VKAs
description: Difference in elastin degradation rate before and after discontinuation of VKAs, quantified by the change in plasma desmosine levels
measure: Difference in vitamin K status
time frame: Plasma dp-ucMGP is measured at baseline and 6 months after discontinuation of VKAs
description: Difference in vitamin K status before and after discontinuation of VKAs, quantified by the change in dp-ucMGP, discontinuation of VKAs.
measure: Association between desmosine and dp-ucMGP
time frame: Desmosine and dp-ucMGP are determined before discontinuation of VKAs and 6 months after discontinuation of VKAs
description: Association between desmosine and dp-ucMGP both in patients who use VKAs and do not use VKAs.
measure: Differences in desmosine and dp-ucMGP levels between different VKORC1 polymorphisms
time frame: Desmosine and dp-ucMGP are determined, both before discontinuation of VKAs and 6 months after discontinuation of VKAs. VKORC1 polymorphisms are determined before discontinuation of VKAs.
description: Levels of dp-ucMGP and desmosine levels of subjects with different VKORC1 polymorphisms are compared, both during the use of VKAs and after discontinuation.
intervention type: Diagnostic Test
intervention name: Venipuncture
description: Approximately 6 months after discontinuation of VKAs one additional venipuncture will be performed for determination of dp-ucMGP and desmosine.
At baseline two additional blood collection tubes will be drawn for determination of dp-ucMGP, desmosine and VKORC1 polymorphisms. Since this is during one of the last regular International Normalized Ratio (INR) testing at the anticoagulation clinic, no additional venipuncture has to be performed at this moment.
-  at baseline: blood sample of 15mL (EDTA-plasma), divided in four two portions (one for
           determination of dp-ucMGP and one for desmosine)

        -  at baseline: blood sample of 10mL (EDTA-plasma). DNA will be isolated from these samples
           for determination of the VKORC1 polymorphisms

        -  after six months: blood sample of 15mL (EDTA-plasma), divided in four two portions (one
           for determination of dp-ucMGP and one for desmosine)
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rob Janssen, MD, PhD
role: Principal Investigator
affiliation: Canisius-Wilhelmina Hospital
last name: Rob Janssen, MD, PhD
phone: +31-24-3658755
email: rob.janssen@cwz.nl
last name: Ianthe Piscaer, MD
phone: +31-43-3875051
email: ianthe.piscaer@mumc.nl
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: Netherlands
citation: Mithieux SM, Weiss AS. Elastin. Adv Protein Chem. 2005;70:437-61. doi: 10.1016/S0065-3233(05)70013-9.
PMID: 15837523
citation: Robert L, Robert AM, Fulop T. Rapid increase in human life expectancy: will it soon be limited by the aging of elastin? Biogerontology. 2008 Apr;9(2):119-33. doi: 10.1007/s10522-007-9122-6. Epub 2008 Jan 4.
PMID: 18175202
citation: Bouvet C, Moreau S, Blanchette J, de Blois D, Moreau P. Sequential activation of matrix metalloproteinase 9 and transforming growth factor beta in arterial elastocalcinosis. Arterioscler Thromb Vasc Biol. 2008 May;28(5):856-62. doi: 10.1161/ATVBAHA.107.153056. Epub 2008 Feb 21.
PMID: 18292396
citation: Basalyga DM, Simionescu DT, Xiong W, Baxter BT, Starcher BC, Vyavahare NR. Elastin degradation and calcification in an abdominal aorta injury model: role of matrix metalloproteinases. Circulation. 2004 Nov 30;110(22):3480-7. doi: 10.1161/01.CIR.0000148367.08413.E9. Epub 2004 Nov 15.
PMID: 15545515
citation: Turino GM, Ma S, Lin YY, Cantor JO, Luisetti M. Matrix elastin: a promising biomarker for chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2011 Sep 15;184(6):637-41. doi: 10.1164/rccm.201103-0450PP.
PMID: 21757624
citation: Maclay JD, McAllister DA, Rabinovich R, Haq I, Maxwell S, Hartland S, Connell M, Murchison JT, van Beek EJ, Gray RD, Mills NL, Macnee W. Systemic elastin degradation in chronic obstructive pulmonary disease. Thorax. 2012 Jul;67(7):606-12. doi: 10.1136/thoraxjnl-2011-200949. Epub 2012 Feb 28.
PMID: 22374923
citation: Williams MC, Murchison JT, Edwards LD, Agusti A, Bakke P, Calverley PM, Celli B, Coxson HO, Crim C, Lomas DA, Miller BE, Rennard S, Silverman EK, Tal-Singer R, Vestbo J, Wouters E, Yates JC, van Beek EJ, Newby DE, MacNee W; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Coronary artery calcification is increased in patients with COPD and associated with increased morbidity and mortality. Thorax. 2014 Aug;69(8):718-23. doi: 10.1136/thoraxjnl-2012-203151. Epub 2014 Jan 28.
PMID: 24473329
citation: Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5. doi: 10.1093/jn/134.11.3100.
PMID: 15514282
citation: Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial. Thromb Haemost. 2015 May;113(5):1135-44. doi: 10.1160/TH14-08-0675. Epub 2015 Feb 19.
PMID: 25694037
citation: Patillon B, Luisi P, Blanche H, Patin E, Cann HM, Genin E, Sabbagh A. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans. PLoS One. 2012;7(12):e53049. doi: 10.1371/journal.pone.0053049. Epub 2012 Dec 28.
PMID: 23285254
citation: Rabinovich RA, Miller BE, Wrobel K, Ranjit K, Williams MC, Drost E, Edwards LD, Lomas DA, Rennard SI, Agusti A, Tal-Singer R, Vestbo J, Wouters EF, John M, van Beek EJ, Murchison JT, Bolton CE, MacNee W, Huang JT; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD. Eur Respir J. 2016 May;47(5):1365-73. doi: 10.1183/13993003.01824-2015. Epub 2016 Mar 23.
PMID: 27009168
responsible party type: Principal Investigator
investigator affiliation: Canisius-Wilhelmina Hospital
investigator full name: Rob Janssen
investigator title: MD, PhD
mesh term: Cystic Fibrosis
mesh term: Alpha 1-Antitrypsin Deficiency
mesh term: Aneurysm
mesh term: Emphysema
sharing ipd: Undecided
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