<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/NCT03010956</url>
  </required_header>
  <id_info>
    <org_study_id>S-DM-ATTIKON</org_study_id>
    <nct_id>NCT03010956</nct_id>
  </id_info>
  <brief_title>Changes in Arterial Stiffness and Endothelial Glycocalyx in Patients With Poorly Controlled Diabetes Mellitus Type 1 or Type 2 After Optimization of Antidiabetic Medication.</brief_title>
  <official_title>Changes in Arterial Stiffness and Endothelial Glycocalyx in Patients With Poorly Controlled Diabetes Mellitus Type 1 or Type 2 After Optimization of Antidiabetic Medication.</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 purpose of this study is to investigate changes in arterial&#xD;
      stiffness and endothelial glycocalyx thickness in patients with poorly controlled diabetes&#xD;
      mellitus type 1 or type 2 after glycemic control by optimal medication.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators will study two groups matched for age and sex: 30 patients with&#xD;
      uncontrolled type 1 diabetes and 30 patients with uncontrolled type 2 diabetes. Individuals&#xD;
      should not be treated with statins, beta-blockers, ACE inhibitors, sartans, hormonal&#xD;
      preparations, drugs that interfere with the function of platelets and hemostasis.&#xD;
      Furthermore, they should not have heart failure, nephropathy and retinopathy. 10 people will&#xD;
      remain uncontrolled after the expiration of 3 months after the modification of antidiabetic&#xD;
      medication used as a control group .&#xD;
&#xD;
      At 0, 3, 6 and 12 months the investigators will measure:&#xD;
&#xD;
        1. Carotid-femoral pulse wave velocity (PWV, m/sec) and augmentation index (AI%) by the&#xD;
           method of arteriography (Arteriograph, TensioMed) and Complior (SP ALAM).&#xD;
&#xD;
        2. Perfused 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;
           glucocalyx thickness.&#xD;
&#xD;
        3. Flow mediated dilatation (FMD) of the brachial artery.&#xD;
&#xD;
        4. Determination of following parameters in blood: glucose, insulin, free fatty acids,&#xD;
           triglycerides, glycerol, C-reactive protein (CRP), transforming growth factor-b (TGF-b),&#xD;
           Lipoprotein-Associated Phospholipase A2 (LP-LPA2), tumor necrosis factor-a (TNF-a), IL6&#xD;
           and IL10 (interleukins), propeptide of type I procollagen (PIP), propeptide of&#xD;
           procollagen type III (PIIINP), matrix metallopeptidases 9 and 2 (MMP), macrophage-colony&#xD;
           stimulating factor (MCSF), growth differentiation factor-15 (GDF-15), N-terminal pro&#xD;
           b-type natriuretic peptide (NT-proBNP) and galectin-3.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2014</start_date>
  <completion_date type="Actual">November 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Crossover</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Differences in pulse wave velocity at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.</measure>
    <time_frame>Baseline, 3 months, 6 months, and 12 months.</time_frame>
    <description>Differences in pulse wave velocity (PWV, m/sec) using tonometry at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Differences in augmentation index at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.</measure>
    <time_frame>Baseline, 3 months, 6 months, and 12 months.</time_frame>
    <description>Differences in augmentation index (AI,%) using oscillometry at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Differences in endothelial glycocalyx at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.</measure>
    <time_frame>Baseline, 3 months, 6 months, and 12 months.</time_frame>
    <description>Differences in endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication. High PBR values represent reduced glycocalyx thickness.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Differences in flow mediated dilation (FMD) at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.</measure>
    <time_frame>Baseline, 3 months, 6 months, and 12 months.</time_frame>
    <description>Differences in flow mediated dilatation (FMD) of the brachial artery at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Endothelial glycocalyx and pulse wave velocity.</measure>
    <time_frame>Baseline, 3 months, 6 months, and 12 months.</time_frame>
    <description>Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with pulse wave velocity (PWV, m/sec) after optimization of antidiabetic medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial glycocalyx and coronary flow reserve.</measure>
    <time_frame>Baseline, 3 months, 6 months, and 12 months.</time_frame>
    <description>Association of endothelial glycocalyx as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with coronary flow reserve (CFR) after optimization of antidiabetic medication.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">100</enrollment>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Patients with uncontrolled diabetes mellitus</arm_group_label>
    <description>Patients with uncotrolled tyre 1 or type 2 diabetes mellitus</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients with controlled diabetes mellitus</arm_group_label>
    <description>Patients with controlled type 1 or type 2 diabetes mellitus</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will consist of 30 patients with uncontrolled type 1 diabetes and 30&#xD;
        patients with uncontrolled type 2 diabetes.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with uncontrolled diabetes mellitus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  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;
&#xD;
          -  treatment with statins, beta- blockers, ACE inhibitors or sartans&#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>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>Constantinos Tymbas, 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>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>October 9, 2018</last_update_submitted>
  <last_update_submitted_qc>October 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2018</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>Associate 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>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03010956
org study id: S-DM-ATTIKON
nct id: NCT03010956
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 purpose of this study is to investigate changes in arterial
      stiffness and endothelial glycocalyx thickness in patients with poorly controlled diabetes
      mellitus type 1 or type 2 after glycemic control by optimal medication.
The investigators will study two groups matched for age and sex: 30 patients with
      uncontrolled type 1 diabetes and 30 patients with uncontrolled type 2 diabetes. Individuals
      should not be treated with statins, beta-blockers, ACE inhibitors, sartans, hormonal
      preparations, drugs that interfere with the function of platelets and hemostasis.
      Furthermore, they should not have heart failure, nephropathy and retinopathy. 10 people will
      remain uncontrolled after the expiration of 3 months after the modification of antidiabetic
      medication used as a control group .

      At 0, 3, 6 and 12 months the investigators will measure:

        1. Carotid-femoral pulse wave velocity (PWV, m/sec) and augmentation index (AI%) by the
           method of arteriography (Arteriograph, TensioMed) and Complior (SP ALAM).

        2. Perfused 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
           glucocalyx thickness.

        3. Flow mediated dilatation (FMD) of the brachial artery.

        4. Determination of following parameters in blood: glucose, insulin, free fatty acids,
           triglycerides, glycerol, C-reactive protein (CRP), transforming growth factor-b (TGF-b),
           Lipoprotein-Associated Phospholipase A2 (LP-LPA2), tumor necrosis factor-a (TNF-a), IL6
           and IL10 (interleukins), propeptide of type I procollagen (PIP), propeptide of
           procollagen type III (PIIINP), matrix metallopeptidases 9 and 2 (MMP), macrophage-colony
           stimulating factor (MCSF), growth differentiation factor-15 (GDF-15), N-terminal pro
           b-type natriuretic peptide (NT-proBNP) and galectin-3.
observational model: Case-Crossover
time perspective: Prospective
measure: Differences in pulse wave velocity at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
time frame: Baseline, 3 months, 6 months, and 12 months.
description: Differences in pulse wave velocity (PWV, m/sec) using tonometry at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
measure: Differences in augmentation index at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
time frame: Baseline, 3 months, 6 months, and 12 months.
description: Differences in augmentation index (AI,%) using oscillometry at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
measure: Differences in endothelial glycocalyx at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
time frame: Baseline, 3 months, 6 months, and 12 months.
description: Differences in endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication. High PBR values represent reduced glycocalyx thickness.
measure: Differences in flow mediated dilation (FMD) at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
time frame: Baseline, 3 months, 6 months, and 12 months.
description: Differences in flow mediated dilatation (FMD) of the brachial artery at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
measure: Endothelial glycocalyx and pulse wave velocity.
time frame: Baseline, 3 months, 6 months, and 12 months.
description: Association of endothelial glycocalyx thickness as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with pulse wave velocity (PWV, m/sec) after optimization of antidiabetic medication.
measure: Endothelial glycocalyx and coronary flow reserve.
time frame: Baseline, 3 months, 6 months, and 12 months.
description: Association of endothelial glycocalyx as assessed by perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels with coronary flow reserve (CFR) after optimization of antidiabetic medication.
arm group label: Patients with uncontrolled diabetes mellitus
description: Patients with uncotrolled tyre 1 or type 2 diabetes mellitus
arm group label: Patients with controlled diabetes mellitus
description: Patients with controlled type 1 or type 2 diabetes mellitus
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: Fotini Kousathana, MD
role: Principal Investigator
affiliation: 2nd Department of Internal Medicine, University of Athens, Greece
last name: Constantinos Tymbas, 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: Associate Professor in Cardiology
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No