<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/NCT02265016</url>
  </required_header>
  <id_info>
    <org_study_id>RBC in CAD</org_study_id>
    <secondary_id>13-037</secondary_id>
    <nct_id>NCT02265016</nct_id>
  </id_info>
  <brief_title>Regulation and Signaling of Red Blood Cell (RBC) Endothelial Nitric Oxide Synthase (eNOS) in Patients With Stable and Unstable Coronary Artery Disease</brief_title>
  <official_title>Regulation and Signaling of RBC-eNOS in Patients With Stable and Unstable Coronary Artery Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heinrich-Heine University, Duesseldorf</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Heinrich-Heine University, Duesseldorf</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is measurement of expression and activity of RBC eNOS in different&#xD;
      clinical cohorts of patients with coronary artery disease and acute coronary syndrome and to&#xD;
      investigate the importance of the NO-stimulated reaction cascade in terms of sGC and PKG.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Actual">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of red cell endothelial nitric oxide-synthase (eNOS)-expression and - activity</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Deformability and stability of red blood cell membrane</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
    <description>by Laser assisted Optical Rotational Cell Analyzer (LORCA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microvascular function</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
    <description>Determination of microvascular function with Laser-Doppler Perfusion Imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peripheral and central hemodynamic measurement</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of arterial stiffness</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
    <description>Determination of arterial stiffness with pulse wave analysis during blood pressure measurement or echocardiography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>determination of flow-mediated dilation</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of nitrate and nitrite in blood plasma and red blood cells (RBC)</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of nitric oxide and cyclic guanosine monophosphate (cGMP) in blood plasma and in red blood cells</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of endothelial microparticles</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Electrocardiogram</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aging and turnover of red blood cells</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Redox status of red blood cells</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
    <description>Determination of redox status of red blood cells will be measured on free thiole with thioltracker and reactive oxygen species( ROS) by dihydrodichlorofluorescein</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aggregation of red blood cells</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
    <description>Determination of aggregation of red blood cells with LORCA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Platelet aggregometry</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression and function of soluble guanylyl cyclase (sGC) in red blood cells</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
    <description>measurement of enzyme expression and activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Expression and activity of Protein Kinase G (PKG)</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
    <description>measurement of enzyme expression and activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determination of leucocyte populations and leucocyte function</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
    <description>flow-cytometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of tetrahydrobiopterin-metabolism</measure>
    <time_frame>baseline, 3 hours and 3 month</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">300</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Endothelial NO-synthase</condition>
  <arm_group>
    <arm_group_label>Patients with CAD</arm_group_label>
    <description>Patients with stable coronary artery disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with ACS</arm_group_label>
    <description>Patients with acute coronar syndrome, instable Angina pectoris and low-risk NSTEMI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>healthy control group</arm_group_label>
    <description>healthy control group without clinical apparent arteriosclerosis</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        3 groups:&#xD;
&#xD;
          -  ACS group (100 Patients)&#xD;
&#xD;
          -  stable CAD group (100 Patients)&#xD;
&#xD;
          -  healthy control group (100 Healthy Volunteers)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  informed consent&#xD;
&#xD;
          -  for ACS(acute coronary syndrome)-Group: angiographic coronary artery disease; acute&#xD;
             coronary syndrome, defined by EITHER unstable angina pectoris with significant&#xD;
             coronary stenosis (troponin negative, without significant ST-elevation) OR low-risk&#xD;
             NSTEMI (Troponin positive, without significant ST-elevation)&#xD;
&#xD;
          -  for stable CAD-Group: angiographic coronary artery disease; no acute coronary syndrome&#xD;
             within the last 3 months&#xD;
&#xD;
          -  healthy control group: No clinical or angiographical signs of apparent atherosclerosis&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  acute inflammation (CRP &gt; 1 mg/dl, leukocyte &gt; 11.000/µl)&#xD;
&#xD;
          -  malignant diseases&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  medication with NO-donors ( e.g.isosorbide mononitrate, isosorbide dinitrate, glyceryl&#xD;
             trinitrate, Molsidomin, Ranexa)&#xD;
&#xD;
          -  patients with STEMI or high-risk NSTEMI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Malte Kelm, Prof. MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Cardiology, Pneumology and Angiology, University Hospital Duesseldorf</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Duesseldorf</name>
      <address>
        <city>Duesseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>October 9, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>February 15, 2021</last_update_submitted>
  <last_update_submitted_qc>February 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Heinrich-Heine University, Duesseldorf</investigator_affiliation>
    <investigator_full_name>Klinik für Kardiologie, Pneumologie und Angiologie</investigator_full_name>
    <investigator_title>Principle Investigator Prof. Dr. Malte Kelm</investigator_title>
  </responsible_party>
  <keyword>coronary artery disease</keyword>
  <keyword>acute coronary syndrome</keyword>
  <keyword>angina pectoris</keyword>
  <keyword>non-ST-segment elevation myocardial infarction</keyword>
  <keyword>red blood cells</keyword>
  <keyword>erythrocytes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</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/NCT02265016
org study id: RBC in CAD
secondary id: 13-037
nct id: NCT02265016
lead sponsor: 
has dmc: No
The aim of this study is measurement of expression and activity of RBC eNOS in different
      clinical cohorts of patients with coronary artery disease and acute coronary syndrome and to
      investigate the importance of the NO-stimulated reaction cascade in terms of sGC and PKG.
observational model: Cohort
time perspective: Other
measure: Determination of red cell endothelial nitric oxide-synthase (eNOS)-expression and - activity
time frame: baseline, 3 hours and 3 month
measure: Deformability and stability of red blood cell membrane
time frame: baseline, 3 hours and 3 month
description: by Laser assisted Optical Rotational Cell Analyzer (LORCA)
measure: Microvascular function
time frame: baseline, 3 hours and 3 month
description: Determination of microvascular function with Laser-Doppler Perfusion Imaging
measure: Peripheral and central hemodynamic measurement
time frame: baseline, 3 hours and 3 month
measure: Determination of arterial stiffness
time frame: baseline, 3 hours and 3 month
description: Determination of arterial stiffness with pulse wave analysis during blood pressure measurement or echocardiography.
measure: determination of flow-mediated dilation
time frame: baseline, 3 hours and 3 month
measure: Determination of nitrate and nitrite in blood plasma and red blood cells (RBC)
time frame: baseline, 3 hours and 3 month
measure: Determination of nitric oxide and cyclic guanosine monophosphate (cGMP) in blood plasma and in red blood cells
time frame: baseline, 3 hours and 3 month
measure: Determination of endothelial microparticles
time frame: baseline, 3 hours and 3 month
measure: Electrocardiogram
time frame: baseline, 3 hours and 3 month
measure: Aging and turnover of red blood cells
time frame: baseline, 3 hours and 3 month
measure: Redox status of red blood cells
time frame: baseline, 3 hours and 3 month
description: Determination of redox status of red blood cells will be measured on free thiole with thioltracker and reactive oxygen species( ROS) by dihydrodichlorofluorescein
measure: Aggregation of red blood cells
time frame: baseline, 3 hours and 3 month
description: Determination of aggregation of red blood cells with LORCA
measure: Platelet aggregometry
time frame: baseline, 3 hours and 3 month
measure: Expression and function of soluble guanylyl cyclase (sGC) in red blood cells
time frame: baseline, 3 hours and 3 month
description: measurement of enzyme expression and activity
measure: Expression and activity of Protein Kinase G (PKG)
time frame: baseline, 3 hours and 3 month
description: measurement of enzyme expression and activity
measure: Determination of leucocyte populations and leucocyte function
time frame: baseline, 3 hours and 3 month
description: flow-cytometry
measure: Changes of tetrahydrobiopterin-metabolism
time frame: baseline, 3 hours and 3 month
arm group label: Patients with CAD
description: Patients with stable coronary artery disease
arm group label: Patients with ACS
description: Patients with acute coronar syndrome, instable Angina pectoris and low-risk NSTEMI
arm group label: healthy control group
description: healthy control group without clinical apparent arteriosclerosis
blood samples
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Malte Kelm, Prof. MD
role: Principal Investigator
affiliation: Department of Cardiology, Pneumology and Angiology, University Hospital Duesseldorf
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Heinrich-Heine University, Duesseldorf
investigator full name: Klinik für Kardiologie, Pneumologie und Angiologie
investigator title: Principle Investigator Prof. Dr. Malte Kelm
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease