<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/NCT02244736</url>
  </required_header>
  <id_info>
    <org_study_id>K-DM-ATTIKON</org_study_id>
    <nct_id>NCT02244736</nct_id>
  </id_info>
  <brief_title>Vascular Markers During OGTT in Diabetics and First-degree Relatives</brief_title>
  <official_title>Changes of the Endothelial Glycocalyx, the Elastic Properties of the Arteries and the Coronary Flow Reserve (CFR) During Oral Glucose Tolerance Test in Patients With New Onset Diabetes Mellitus and First-degree Relatives</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Athens</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Arterial stiffness is associated with increased risk for cardiovascular disease. Moreover,&#xD;
      the integrity of endothelial glycocalyx plays a vital role in vascular permeability,&#xD;
      inflammation and elasticity. The association between damage of endothelial glycocalyx,&#xD;
      impaired arterial elastic properties, and CFR in diabetics and first degree relatives has not&#xD;
      been explored. The purpose of this study is to explore the association between damage of&#xD;
      endothelial glycocalyx, impaired arterial elastic properties, and CFR in diabetics and&#xD;
      first-degree relatives before and after during oral glucose tolerance test (OGTT).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators plan to examine 90 subjects without known diabetes a standard 75-gr oral&#xD;
      glucose tolerance test (OGTT) will be performed. [30 first degree relatives of diabetics with&#xD;
      normal OGTT (relatives), 30 with normal OGTT and no family history of diabetes (normals), and&#xD;
      30 with abnormal OGTT (diabetics) matched for age and sex].&#xD;
&#xD;
      Plasma glucose and serum insulin levels will be measured in venous blood collected at 0, 30,&#xD;
      60, 90 and 120min after glucose loading. At the same time intervals, the investigators will&#xD;
      measure:&#xD;
&#xD;
        1. the carotid to femoral pulse wave velocity (PWVc) using the Complior apparatus&#xD;
&#xD;
        2. the aortic pulse wave velocity (PWVa), central systolic blood pressure (cSBP) and&#xD;
           augmentation index (AI) using an oscillometric method (Arteriograph,TensioMed) as&#xD;
           markers of arterial stiffness and wave reflections&#xD;
&#xD;
        3. the coronary flow reserve (CFR) at baseline and after adenosine infusion (140 μg × kg-1&#xD;
           × min-1) for 3 minutes to assess coronary vasomotor function&#xD;
&#xD;
        4. the perfusion boundary region (PBR- micrometers) of the sublingual arterial microvessels&#xD;
           (ranged from 5-25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck).&#xD;
           Increased PBR is considered an accurate non invasive index of reduced endothelial&#xD;
           glycocalyx thickness.&#xD;
&#xD;
      In addition, the investigators will measure free fatty acids, triglycerides, glycerol, C&#xD;
      reactive protein (CRP), transforming growth factor-b (TGF-b), Lipoprotein-Associated&#xD;
      Phospholipase A2, (LP-LPA2), tumor necrosis factor (TNF-a), interleukin 6 (IL6) and&#xD;
      interleukin 10 (IL10) propeptide of type I procollagen, (PIP), propeptide of procollagen type&#xD;
      III (PIIINP), matrix metallopeptidases 9 and 2 (MMP 9 and 2), macrophage-colony stimulating&#xD;
      factor ( MCSF).&#xD;
&#xD;
      The investigators will measure insulin resistance a) after fasting, using homeostatic model&#xD;
      assessment (HOMA) and hepatic insulin sensitivity (HIS) b) during oral glucose tolerance test&#xD;
      (OGTT) using Matsuda index and insulin sensitivity index (ISI). The investigators will&#xD;
      categorize patients in those with normal (&lt;140 mg/dl at 120 min) and those with abnormal OGTT&#xD;
      (&gt;200mg/dl at 120min).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <target_duration>2 Years</target_duration>
  <primary_outcome>
    <measure>Differences of vascular function at baseline and during OGTT among the 3 groups.</measure>
    <time_frame>Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.</time_frame>
    <description>Differences of pulse wave velocity, augmentation index and central aortic blood pressure at baseline and during OGTT among the 3 groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Differences of endothelial function at baseline and during OGTT among the 3 groups.</measure>
    <time_frame>Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.</time_frame>
    <description>Differences of coronary flow reserve and endothelial glycocalyx thickness at baseline and during OGTT among the 3 groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Insulin resistance and arterial stiffness</measure>
    <time_frame>Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.</time_frame>
    <description>Association of insulin resistance with changes of pulse wave velocity, augmentation index and central aortic blood pressure during OGTT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin resistance and endothelial function</measure>
    <time_frame>Baseline, 30 min, 60 min, 90 min,120 min of OGTT</time_frame>
    <description>Association of insulin resistance with changes of coronary flow reserve and endothelial glycocalyx during OGTT</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Subjects with no family history of diabetes mellitus and normal OGTT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Relatives</arm_group_label>
    <description>First-degree relatives of patients with diabetes mellitus and normal OGTT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetics</arm_group_label>
    <description>Subjects with abnormal OGTT</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Plasma in serum for fibrosis and inflammatory markers&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        90 subjects, 30 first degree relatives of diabetics withnormal OGTT (relatives), 30&#xD;
        withnormal OGTT and no family history of diabetes (normals), and 30 with abnormal OGTT&#xD;
        (diabetics).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  subjects without known diabetes&#xD;
&#xD;
          -  first degree relatives of diabetics&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  coronary or valvular heart disease&#xD;
&#xD;
          -  congestive heart failure&#xD;
&#xD;
          -  peripheral vascular disease&#xD;
&#xD;
          -  liver or kidney failure&#xD;
&#xD;
          -  history of alcohol or drug abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ignatios Ikonomidis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Cardiology Department, University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>George Pavlidis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Cardiology Department, University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vaia Lambadiari, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Department of Internal Medicine , University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Charalambos Koukoulis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Cardiology Department, University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fotini Kousathana, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Department of Internal Medicine, University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Maria Varoudi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Cardiology Department, University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vlasios Tritakis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Cardiology Department, University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Helen Triantafyllidi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Cardiology Department, University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>George Dimitriadis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Department of Internal Medicine, University of Athens, Greece</affiliation>
  </overall_official>
  <overall_official>
    <last_name>John Lekakis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>2nd Cardiology Department, University of Athens, Greece</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>''Attikon'' University General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>12462</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2014</study_first_posted>
  <last_update_submitted>February 28, 2019</last_update_submitted>
  <last_update_submitted_qc>February 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Athens</investigator_affiliation>
    <investigator_full_name>Ignatios Ikonomidis</investigator_full_name>
    <investigator_title>Assistant Professor in Cardiology</investigator_title>
  </responsible_party>
  <keyword>Arterial stiffness</keyword>
  <keyword>Endothelial glycocalyx</keyword>
  <keyword>Coronary flow reserve</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</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/NCT02244736
org study id: K-DM-ATTIKON
nct id: NCT02244736
lead sponsor: 
has dmc: Yes
Arterial stiffness is associated with increased risk for cardiovascular disease. Moreover,
      the integrity of endothelial glycocalyx plays a vital role in vascular permeability,
      inflammation and elasticity. The association between damage of endothelial glycocalyx,
      impaired arterial elastic properties, and CFR in diabetics and first degree relatives has not
      been explored. The purpose of this study is to explore the association between damage of
      endothelial glycocalyx, impaired arterial elastic properties, and CFR in diabetics and
      first-degree relatives before and after during oral glucose tolerance test (OGTT).
The investigators plan to examine 90 subjects without known diabetes a standard 75-gr oral
      glucose tolerance test (OGTT) will be performed. [30 first degree relatives of diabetics with
      normal OGTT (relatives), 30 with normal OGTT and no family history of diabetes (normals), and
      30 with abnormal OGTT (diabetics) matched for age and sex].

      Plasma glucose and serum insulin levels will be measured in venous blood collected at 0, 30,
      60, 90 and 120min after glucose loading. At the same time intervals, the investigators will
      measure:

        1. the carotid to femoral pulse wave velocity (PWVc) using the Complior apparatus

        2. the aortic pulse wave velocity (PWVa), central systolic blood pressure (cSBP) and
           augmentation index (AI) using an oscillometric method (Arteriograph,TensioMed) as
           markers of arterial stiffness and wave reflections

        3. the coronary flow reserve (CFR) at baseline and after adenosine infusion (140 μg × kg-1
           × min-1) for 3 minutes to assess coronary vasomotor function

        4. the perfusion boundary region (PBR- micrometers) of the sublingual arterial microvessels
           (ranged from 5-25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck).
           Increased PBR is considered an accurate non invasive index of reduced endothelial
           glycocalyx thickness.

      In addition, the investigators will measure free fatty acids, triglycerides, glycerol, C
      reactive protein (CRP), transforming growth factor-b (TGF-b), Lipoprotein-Associated
      Phospholipase A2, (LP-LPA2), tumor necrosis factor (TNF-a), interleukin 6 (IL6) and
      interleukin 10 (IL10) propeptide of type I procollagen, (PIP), propeptide of procollagen type
      III (PIIINP), matrix metallopeptidases 9 and 2 (MMP 9 and 2), macrophage-colony stimulating
      factor ( MCSF).

      The investigators will measure insulin resistance a) after fasting, using homeostatic model
      assessment (HOMA) and hepatic insulin sensitivity (HIS) b) during oral glucose tolerance test
      (OGTT) using Matsuda index and insulin sensitivity index (ISI). The investigators will
      categorize patients in those with normal (<140 mg/dl at 120 min) and those with abnormal OGTT
      (>200mg/dl at 120min).
observational model: Case-Control
time perspective: Cross-Sectional
measure: Differences of vascular function at baseline and during OGTT among the 3 groups.
time frame: Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.
description: Differences of pulse wave velocity, augmentation index and central aortic blood pressure at baseline and during OGTT among the 3 groups.
measure: Differences of endothelial function at baseline and during OGTT among the 3 groups.
time frame: Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.
description: Differences of coronary flow reserve and endothelial glycocalyx thickness at baseline and during OGTT among the 3 groups.
measure: Insulin resistance and arterial stiffness
time frame: Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.
description: Association of insulin resistance with changes of pulse wave velocity, augmentation index and central aortic blood pressure during OGTT
measure: Insulin resistance and endothelial function
time frame: Baseline, 30 min, 60 min, 90 min,120 min of OGTT
description: Association of insulin resistance with changes of coronary flow reserve and endothelial glycocalyx during OGTT
arm group label: Controls
description: Subjects with no family history of diabetes mellitus and normal OGTT
arm group label: Relatives
description: First-degree relatives of patients with diabetes mellitus and normal OGTT
arm group label: Diabetics
description: Subjects with abnormal OGTT
Plasma in serum for fibrosis and inflammatory markers
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ignatios Ikonomidis, MD
role: Principal Investigator
affiliation: 2nd Cardiology Department, University of Athens, Greece
last name: George Pavlidis, MD
role: Principal Investigator
affiliation: 2nd Cardiology Department, University of Athens, Greece
last name: Vaia Lambadiari, MD
role: Principal Investigator
affiliation: 2nd Department of Internal Medicine , University of Athens, Greece
last name: Charalambos Koukoulis, MD
role: Principal Investigator
affiliation: 2nd Cardiology Department, University of Athens, Greece
last name: Fotini Kousathana, MD
role: Principal Investigator
affiliation: 2nd Department of Internal Medicine, University of Athens, Greece
last name: Maria Varoudi, MD
role: Principal Investigator
affiliation: 2nd Cardiology Department, University of Athens, Greece
last name: Vlasios Tritakis, MD
role: Principal Investigator
affiliation: 2nd Cardiology Department, University of Athens, Greece
last name: Helen Triantafyllidi, MD
role: Principal Investigator
affiliation: 2nd Cardiology Department, University of Athens, Greece
last name: George Dimitriadis, MD
role: Principal Investigator
affiliation: 2nd Department of Internal Medicine, University of Athens, Greece
last name: John Lekakis, MD
role: Principal Investigator
affiliation: 2nd Cardiology Department, University of Athens, Greece
facility: 
country: Greece
responsible party type: Principal Investigator
investigator affiliation: University of Athens
investigator full name: Ignatios Ikonomidis
investigator title: Assistant Professor in Cardiology
mesh term: Diabetes Mellitus