<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/NCT03301129</url>
  </required_header>
  <id_info>
    <org_study_id>3241</org_study_id>
    <nct_id>NCT03301129</nct_id>
  </id_info>
  <brief_title>Role of Traditional Cigarettes, Electronic and IQOS Cigarettes on Oxidative Stress.</brief_title>
  <official_title>Effects on Oxidative Stress and Platelet Activation of Traditional Cigarettes, E-cigarettes and IQOS Cigarettes: A Randomized in Vivo Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Roma La Sapienza</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Coluzzi Flaminia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Peruzzi Mariangela</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nocella Cristina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Loffredo Lorenzo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Marullo Antonino G.M.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Valenti Valentina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Chimenti Isotta</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>De Falco Elena</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sciarretta Sebastiano</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Roma La Sapienza</source>
  <oversight_info>
    <has_dmc>Yes</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 cigarettes (E-cigarettes) and new heat-not-burn tobacco products such as IQOS®, an&#xD;
      electronic device that heats a cigarette-like stick without combustion, are a modern and&#xD;
      technological surrogate of traditional tobacco cigarettes (T-cigarettes), that are entering&#xD;
      in the commercial market. While the negative effects of the traditional cigarette are well&#xD;
      known, little data are reported in scientific literature on the risks on the health by these&#xD;
      new smoking devices. Endothelial dysfunction evaluated by flow-mediated dilatation (FMD),&#xD;
      oxidative stress and platelet activation have been recognized as a hallmark of preclinical&#xD;
      systemic atherosclerosis and as a useful marker to stratify the risk of cardiovascular&#xD;
      disease in patients at risk or with established clinically significant atherosclerosis. Since&#xD;
      no data are reported about the effects of these new smoking device on oxidative stress,&#xD;
      platelet activation and FMD, the investigators designed a human study assessing if these new&#xD;
      smoking devices have effects on healthy smokers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2017</start_date>
  <completion_date type="Actual">February 25, 2018</completion_date>
  <primary_completion_date type="Actual">January 30, 2018</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>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endothelial dysfunction</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>flow-mediated dilatation (FMD) assessed by vascular ultrasound</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Oxidative stress</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>Soluble Nox2-derived peptide, a direct marker of NADPH oxidase activation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Platelet activation</measure>
    <time_frame>up to 24 weeks</time_frame>
    <description>evaluation of sPselectin, thromboxane and aggregation as markers of platelet activation</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Oxidative Stress Induction</condition>
  <condition>Endothelial Dysfunction</condition>
  <condition>Platelet Activation</condition>
  <arm_group>
    <arm_group_label>Traditional cigarette</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>smoke one Traditional cigarette (with a mean nicotine content of 0.6 mg according to package label) and in a sub-group smoke a sham cigarette (an traditional cigarette without combustion).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Electronic cigarette</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>smoke a tobacco-flavored Electronic cigarette (9 puffs approximately equivalent to 0.6 mg of nicotine content) and in a sub-group smoke a sham cigarette (an electronic cigarette without nicotine).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Heat-not-burn tobacco products (IQOS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>smoke one IQOS cigarette (with a mean nicotine content of 0.6 mg according to package label).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Smoke</intervention_name>
    <description>See arm/group descriptions.</description>
    <arm_group_label>Electronic cigarette</arm_group_label>
    <arm_group_label>Heat-not-burn tobacco products (IQOS)</arm_group_label>
    <arm_group_label>Traditional cigarette</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Smokers volunteers, minimum age 18 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  no history of acute or chronic organic, metabolic and inflammatory diseases;&#xD;
&#xD;
          -  no fever and infections in the last 3 months;&#xD;
&#xD;
          -  no history of cardiovascular pathological symptoms;&#xD;
&#xD;
          -  no allergies;&#xD;
&#xD;
          -  none of the participants took vitamin E, other antioxidant supplements or other drugs&#xD;
             potentially affecting oxidative stress or FMD&#xD;
&#xD;
          -  women were not menstruating when the experiment was performed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giacomo Frati, MD</last_name>
    <role>Study Director</role>
    <affiliation>Sapienza University of Rome, Policlinico Umberto I</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sapienza University</name>
      <address>
        <city>Roma</city>
        <zip>00161</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>September 23, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>March 26, 2018</last_update_submitted>
  <last_update_submitted_qc>March 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Roma La Sapienza</investigator_affiliation>
    <investigator_full_name>Roberto Carnevale</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>identified individual participant data for all outcomes measures will be made available to other reserachers.</ipd_description>
  </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/NCT03301129
org study id: 3241
nct id: NCT03301129
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Electronic cigarettes (E-cigarettes) and new heat-not-burn tobacco products such as IQOS®, an
      electronic device that heats a cigarette-like stick without combustion, are a modern and
      technological surrogate of traditional tobacco cigarettes (T-cigarettes), that are entering
      in the commercial market. While the negative effects of the traditional cigarette are well
      known, little data are reported in scientific literature on the risks on the health by these
      new smoking devices. Endothelial dysfunction evaluated by flow-mediated dilatation (FMD),
      oxidative stress and platelet activation have been recognized as a hallmark of preclinical
      systemic atherosclerosis and as a useful marker to stratify the risk of cardiovascular
      disease in patients at risk or with established clinically significant atherosclerosis. Since
      no data are reported about the effects of these new smoking device on oxidative stress,
      platelet activation and FMD, the investigators designed a human study assessing if these new
      smoking devices have effects on healthy smokers.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Endothelial dysfunction
time frame: up to 24 weeks
description: flow-mediated dilatation (FMD) assessed by vascular ultrasound
measure: Oxidative stress
time frame: up to 24 weeks
description: Soluble Nox2-derived peptide, a direct marker of NADPH oxidase activation
measure: Platelet activation
time frame: up to 24 weeks
description: evaluation of sPselectin, thromboxane and aggregation as markers of platelet activation
arm group label: Traditional cigarette
arm group type: Experimental
description: smoke one Traditional cigarette (with a mean nicotine content of 0.6 mg according to package label) and in a sub-group smoke a sham cigarette (an traditional cigarette without combustion).
arm group label: Electronic cigarette
arm group type: Experimental
description: smoke a tobacco-flavored Electronic cigarette (9 puffs approximately equivalent to 0.6 mg of nicotine content) and in a sub-group smoke a sham cigarette (an electronic cigarette without nicotine).
arm group label: Heat-not-burn tobacco products (IQOS)
arm group type: Experimental
description: smoke one IQOS cigarette (with a mean nicotine content of 0.6 mg according to package label).
intervention type: Behavioral
intervention name: Smoke
description: See arm/group descriptions.
arm group label: Electronic cigarette
arm group label: Heat-not-burn tobacco products (IQOS)
arm group label: Traditional cigarette
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Giacomo Frati, MD
role: Study Director
affiliation: Sapienza University of Rome, Policlinico Umberto I
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Roma La Sapienza
investigator full name: Roberto Carnevale
investigator title: Principal Investigator
sharing ipd: Undecided
ipd description: identified individual participant data for all outcomes measures will be made available to other reserachers.