<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/NCT03039920</url>
  </required_header>
  <id_info>
    <org_study_id>698/11-3-15</org_study_id>
    <nct_id>NCT03039920</nct_id>
  </id_info>
  <brief_title>The Effects of Electronic Cigarette Smoking on the Arterial Wall and Endothelial Glycocalyx Properties of Smokers</brief_title>
  <official_title>The Effects of Electronic Cigarette Smoking on the Arterial Wall and Endothelial Glycocalyx Properties of Smokers</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>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>
      Electronic cigarette is proposed as a bridge to smoking cessation. In this study we examine&#xD;
      its effects on aortic elasticity, glycocalyx integrity, and exhaled carbon monoxide (CO)&#xD;
      concentration and platelet function, both acutely and after 1 month of use.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Two smoker groups matched for age and sex will be assessed:&#xD;
&#xD;
        1. a group of 30 current smokers with no diagnosed cardiovascular disease as the control&#xD;
           group for chronic phase&#xD;
&#xD;
        2. a group of 30 current smokers with no diagnosed cardiovascular disease who will be using&#xD;
           the electronic cigarette with nicotine for 1 month&#xD;
&#xD;
      In the acute phase all 60 smokers will undergo a &quot;sham&quot; smoking for 7 minutes. Afterwards 30&#xD;
      out of 60 smokers will be randomized to smoke either a normal cigarette or an electronic&#xD;
      cigarette with nicotine and after a 60 minute washout period these subjects will be crossed&#xD;
      over to the alternate mode of smoking (electronic with nicotine or normal cigarette&#xD;
      respectively).&#xD;
&#xD;
      The remaining 30 smokers will be randomized to smoke either a normal cigarette or an&#xD;
      electronic cigarette without nicotine and after a 60 minute washout period these subjects&#xD;
      will be crossed over to the alternate mode of smoking (electronic without nicotine or normal&#xD;
      cigarette respectively.&#xD;
&#xD;
      After the completion of the acute phase all 60 smokers will start the use of an electronic&#xD;
      cigarette for one month.&#xD;
&#xD;
      In the acute phase, measurements will be performed at baseline, after sham smoking and after&#xD;
      smoking of the normal or electronic cigarette (with or without nicotine). The chronic phase&#xD;
      measurements will be performed 1 month after use electronic cigarette with nicotine. Thirty&#xD;
      current smokers of similar age and sex will serve as controls and will have measurements at&#xD;
      baseline and 1 month after baseline assessment. The nicotine concentration of the electronic&#xD;
      cigarette fluid used during both phases will be 12 mg/dL, while the participants will be&#xD;
      allowed to use their cigarette of preference in the acute phase. In both phases we will&#xD;
      assess a) the aortic pulse wave velocity (PWV) and augmentation index (AIx) by Arteriograph&#xD;
      and Complior; b) the perfusion boundary region of the sublingual arterial microvessels using&#xD;
      Sideview, Darkfield imaging (Microscan, Glycocheck); c) the exhaled carbon monoxide (CO)&#xD;
      level (parts per million -ppm) as a smoking status marker; d) the vital signs; e) an&#xD;
      electrocardiogram; and f) plasma levels of C- reactive protein (CRP), transforming growth&#xD;
      factor-b (TGF-b), lipoprotein associated phospholipase A2 (LP- LPA2), tumor necrosis factor-&#xD;
      α (TNF-α), interleukins 6 and 10 (IL-6 and -10), procollagen propeptide type III (PIIINP),&#xD;
      matrix metalloproteinase 2 and 9 (MMP-2 and -9), and macrophage-colony stimulating factor&#xD;
      (MCSF), malondialdehyde (MDA) and protein carbonyls (PC) and platelet function tests using&#xD;
      the novel Platelet Function Analyzer PFA-100 and the traditional Light Transmission&#xD;
      Aggregometry (LTA)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 31, 2017</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Acute electronic cigarette vaping effects on arterial stiffness.</measure>
    <time_frame>7 minutes</time_frame>
    <description>Acute electronic cigarette vaping effects on arterial stiffness as assessed by pulse wave velocity (PWV, m/sec). PWV (m/sec) was measured by using tonometry by Complior (Alam Medical, Vincennes, France). Two non-invasive pressure sensors were used to record the carotid and femoral waveforms and the distance between the two arterial sites was measured with a tape measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Acute electronic cigarette vaping effects on endothelial integrity.</measure>
    <time_frame>7 minutes</time_frame>
    <description>Acute electronic cigarette vaping effects on endothelial integrity as assessed by measuring endothelial glycocalyx thickness. We measured the perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25 μm) using Sidestream Darkfield Imaging (Microscan, Glycocheck, Microvascular Health Solutions Inc., Salt Lake City, UT, USA).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chronic electronic cigarette vaping effects on arterial stiffness.</measure>
    <time_frame>1 month</time_frame>
    <description>Chronic electronic cigarette vaping effects on arterial stiffness, as assessed by pulse wave velocity (PWV, m/sec). PWV (m/sec) was measured by using tonometry by Complior (Alam Medical, Vincennes, France). Two non-invasive pressure sensors were used to record the carotid and femoral waveforms and the distance between the two arterial sites was measured with a tape measure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chronic electronic cigarette vaping effects on endothelial integrity.</measure>
    <time_frame>1 month</time_frame>
    <description>Chronic electronic cigarette vaping effects on endothelial integrity as assessed by measuring endothelial glycocalyx thickness. We measured the perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25 μm) using Sidestream Darkfield Imaging (Microscan, Glycocheck, Microvascular Health Solutions Inc., Salt Lake City, UT, USA).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chronic electronic cigarette vaping effects on platelet aggregation.</measure>
    <time_frame>1 month</time_frame>
    <description>Chronic electronic cigarette vaping effects on platelet function as assessed by Light Transmission Aggregometry (LTA). We measured both maximum (peak) and late platelet aggregation (%) (at 6 minutes) after addition of epinephrine (as stimulant) in platelet rich plasma.The 100% line was set using platelet poor plasma and a 0% baseline established with platelet rich plasma before addition of the agonist(epinephrine). Platelet aggregation is experssed as % of the 100% line</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Chronic electronic cigarette vaping effects on high-shear stress-dependent platelet function.</measure>
    <time_frame>1 month</time_frame>
    <description>Chronic electronic cigarette vaping effects on high-shear stress-dependent platelet function as assesed by PFA-100. The instrument estimates the ability of platelets activated in a high shear environment to occlude an aperture in a membrane coated with collagen and epinephrine (CEPI).The time taken for flow across the membrane to stop (closure time, CT, seconds) is recorded as measure of platelet function. Platelet adhesion and aggregation following a vascular injury is simulated in vitro by PFA.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Smoking Cessation</condition>
  <arm_group>
    <arm_group_label>Electronic cigarette with or without nicotine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Electronic cigarette assisted cessation program</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Smoker control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Conventional cigarette smoking continuation</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Electronic cigarette</intervention_name>
    <description>Smoking of electronic cigarette</description>
    <arm_group_label>Electronic cigarette with or without nicotine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional cigarette</intervention_name>
    <description>Smoking tobacco cigarette</description>
    <arm_group_label>Smoker control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Active conventional cigarette smoker&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Health condition adversely affected by smoking, history or presence of cardiovascular&#xD;
             disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ignatios Ikonomidis, Dr</last_name>
    <role>Principal Investigator</role>
    <affiliation>Attikon Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ignatios Ikonomidis, Dr</last_name>
    <phone>00306944805732</phone>
    <email>ignoik@otenet.gr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dimitrios Vlastos, Dr</last_name>
    <phone>00306942446956</phone>
    <email>dimitrisbvr@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>''Attikon'' University General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>12462</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ignatios Ikonomidis, MD</last_name>
      <phone>00302105831264</phone>
    </contact>
    <investigator>
      <last_name>Ignatios Ikonomidis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>January 28, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>April 1, 2020</last_update_submitted>
  <last_update_submitted_qc>April 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2020</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</investigator_title>
  </responsible_party>
  <!-- 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/NCT03039920
org study id: 698/11-3-15
nct id: NCT03039920
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Electronic cigarette is proposed as a bridge to smoking cessation. In this study we examine
      its effects on aortic elasticity, glycocalyx integrity, and exhaled carbon monoxide (CO)
      concentration and platelet function, both acutely and after 1 month of use.
Two smoker groups matched for age and sex will be assessed:

        1. a group of 30 current smokers with no diagnosed cardiovascular disease as the control
           group for chronic phase

        2. a group of 30 current smokers with no diagnosed cardiovascular disease who will be using
           the electronic cigarette with nicotine for 1 month

      In the acute phase all 60 smokers will undergo a "sham" smoking for 7 minutes. Afterwards 30
      out of 60 smokers will be randomized to smoke either a normal cigarette or an electronic
      cigarette with nicotine and after a 60 minute washout period these subjects will be crossed
      over to the alternate mode of smoking (electronic with nicotine or normal cigarette
      respectively).

      The remaining 30 smokers will be randomized to smoke either a normal cigarette or an
      electronic cigarette without nicotine and after a 60 minute washout period these subjects
      will be crossed over to the alternate mode of smoking (electronic without nicotine or normal
      cigarette respectively.

      After the completion of the acute phase all 60 smokers will start the use of an electronic
      cigarette for one month.

      In the acute phase, measurements will be performed at baseline, after sham smoking and after
      smoking of the normal or electronic cigarette (with or without nicotine). The chronic phase
      measurements will be performed 1 month after use electronic cigarette with nicotine. Thirty
      current smokers of similar age and sex will serve as controls and will have measurements at
      baseline and 1 month after baseline assessment. The nicotine concentration of the electronic
      cigarette fluid used during both phases will be 12 mg/dL, while the participants will be
      allowed to use their cigarette of preference in the acute phase. In both phases we will
      assess a) the aortic pulse wave velocity (PWV) and augmentation index (AIx) by Arteriograph
      and Complior; b) the perfusion boundary region of the sublingual arterial microvessels using
      Sideview, Darkfield imaging (Microscan, Glycocheck); c) the exhaled carbon monoxide (CO)
      level (parts per million -ppm) as a smoking status marker; d) the vital signs; e) an
      electrocardiogram; and f) plasma levels of C- reactive protein (CRP), transforming growth
      factor-b (TGF-b), lipoprotein associated phospholipase A2 (LP- LPA2), tumor necrosis factor-
      α (TNF-α), interleukins 6 and 10 (IL-6 and -10), procollagen propeptide type III (PIIINP),
      matrix metalloproteinase 2 and 9 (MMP-2 and -9), and macrophage-colony stimulating factor
      (MCSF), malondialdehyde (MDA) and protein carbonyls (PC) and platelet function tests using
      the novel Platelet Function Analyzer PFA-100 and the traditional Light Transmission
      Aggregometry (LTA)
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Acute electronic cigarette vaping effects on arterial stiffness.
time frame: 7 minutes
description: Acute electronic cigarette vaping effects on arterial stiffness as assessed by pulse wave velocity (PWV, m/sec). PWV (m/sec) was measured by using tonometry by Complior (Alam Medical, Vincennes, France). Two non-invasive pressure sensors were used to record the carotid and femoral waveforms and the distance between the two arterial sites was measured with a tape measure.
measure: Acute electronic cigarette vaping effects on endothelial integrity.
time frame: 7 minutes
description: Acute electronic cigarette vaping effects on endothelial integrity as assessed by measuring endothelial glycocalyx thickness. We measured the perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25 μm) using Sidestream Darkfield Imaging (Microscan, Glycocheck, Microvascular Health Solutions Inc., Salt Lake City, UT, USA).
measure: Chronic electronic cigarette vaping effects on arterial stiffness.
time frame: 1 month
description: Chronic electronic cigarette vaping effects on arterial stiffness, as assessed by pulse wave velocity (PWV, m/sec). PWV (m/sec) was measured by using tonometry by Complior (Alam Medical, Vincennes, France). Two non-invasive pressure sensors were used to record the carotid and femoral waveforms and the distance between the two arterial sites was measured with a tape measure.
measure: Chronic electronic cigarette vaping effects on endothelial integrity.
time frame: 1 month
description: Chronic electronic cigarette vaping effects on endothelial integrity as assessed by measuring endothelial glycocalyx thickness. We measured the perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25 μm) using Sidestream Darkfield Imaging (Microscan, Glycocheck, Microvascular Health Solutions Inc., Salt Lake City, UT, USA).
measure: Chronic electronic cigarette vaping effects on platelet aggregation.
time frame: 1 month
description: Chronic electronic cigarette vaping effects on platelet function as assessed by Light Transmission Aggregometry (LTA). We measured both maximum (peak) and late platelet aggregation (%) (at 6 minutes) after addition of epinephrine (as stimulant) in platelet rich plasma.The 100% line was set using platelet poor plasma and a 0% baseline established with platelet rich plasma before addition of the agonist(epinephrine). Platelet aggregation is experssed as % of the 100% line
measure: Chronic electronic cigarette vaping effects on high-shear stress-dependent platelet function.
time frame: 1 month
description: Chronic electronic cigarette vaping effects on high-shear stress-dependent platelet function as assesed by PFA-100. The instrument estimates the ability of platelets activated in a high shear environment to occlude an aperture in a membrane coated with collagen and epinephrine (CEPI).The time taken for flow across the membrane to stop (closure time, CT, seconds) is recorded as measure of platelet function. Platelet adhesion and aggregation following a vascular injury is simulated in vitro by PFA.
arm group label: Electronic cigarette with or without nicotine
arm group type: Active Comparator
description: Electronic cigarette assisted cessation program
arm group label: Smoker control
arm group type: Active Comparator
description: Conventional cigarette smoking continuation
intervention type: Other
intervention name: Electronic cigarette
description: Smoking of electronic cigarette
arm group label: Electronic cigarette with or without nicotine
intervention type: Other
intervention name: Conventional cigarette
description: Smoking tobacco cigarette
arm group label: Smoker control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ignatios Ikonomidis, Dr
role: Principal Investigator
affiliation: Attikon Hospital
last name: Ignatios Ikonomidis, Dr
phone: 00306944805732
email: ignoik@otenet.gr
last name: Dimitrios Vlastos, Dr
phone: 00306942446956
email: dimitrisbvr@hotmail.com
facility: 
status: Recruiting
contact: 
investigator: 
country: Greece
responsible party type: Principal Investigator
investigator affiliation: University of Athens
investigator full name: Ignatios Ikonomidis
investigator title: Assistant Professor