<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/NCT04452175</url>
  </required_header>
  <id_info>
    <org_study_id>GENESIS, RCT UKRIT</org_study_id>
    <nct_id>NCT04452175</nct_id>
  </id_info>
  <brief_title>Cigarette Consumption After switchinG to High or Low Nicotine strENght E-cigaretteS In Smokers With Schizophrenia</brief_title>
  <acronym>GENESIS</acronym>
  <official_title>Cigarette Consumption After switchinG to High or Low Nicotine strENght E-cigaretteS In Smokers With Schizophrenia Spectrum Disorders: A 12-month Randomised, Double-blind Multicentre Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Catania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Juul Labs, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>St. Petersburg State Pavlov Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bashkir State Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ukrainian Institute on Public Health Policy</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Surrey</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eclat Srl.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Catania</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Smokers with schizophrenia spectrum disorders have high rates of morbidity and mortality from&#xD;
      smoking-related diseases compared with the general population and current options for smoking&#xD;
      cessation in this vulnerable group are unsatisfactory.&#xD;
&#xD;
      Considering that most people with schizophrenia spectrum disorders continue smoking, it is&#xD;
      urgent to consider alternative and more efficient interventions to reduce or prevent their&#xD;
      morbidity and mortality. Switching to combustion-free technologies for nicotine delivery&#xD;
      (I.e. e-cigarettes) could be a pragmatic and much less harmful alternative to tobacco smoking&#xD;
      with the possibility of significant health gains. Emerging research is suggesting that ECs&#xD;
      may be useful for smoking cessation and relapse prevention in people with schizophrenia&#xD;
      spectrum disorders. In particular, a study conducted with JUUL e-cigarette with 5% nicotine&#xD;
      strength showed that this product had sufficient nicotine delivery and product appeal to&#xD;
      determine high success rates in heavy smokers with schizophrenia spectrum disorders.&#xD;
&#xD;
      In consideration of these preliminary findings, we hypothesized that switching smokers with a&#xD;
      schizophrenia spectrum disorder diagnosis to JUUL e-cigarette with 5% nicotine strength could&#xD;
      result in higher success rates compared to JUUL e-cigarette with 1.7% nicotine strength.&#xD;
      Recent work indicates that nicotine PK of the JUUL e-cigarette with 5% nicotine strength (a&#xD;
      device that utilizes a nicotine salt formulation) approximates the nicotine delivery of&#xD;
      combustible cigarettes and that the 5% nicotine strength product is far more efficient in&#xD;
      delivering nicotine compared to the sister product with 1.7% nicotine strength. Both products&#xD;
      are identical in their appearance, making them suitable for a double-blind study design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicenter, 12-months prospective trial, utilizing a randomized, double-blind, 2-arm&#xD;
      parallel, switching design to compare effectiveness, tolerability, acceptability, and pattern&#xD;
      of use between high (JUUL 5% nicotine) and low nicotine strength devices (JUUL 1.7% nicotine)&#xD;
      in adult smokers with schizophrenia spectrum disorders. The study will take place at 5&#xD;
      international sites: UK (London), Italy (Catania), Russia (Ufa and St. Petersburg) and&#xD;
      Ukraine (Kiev).&#xD;
&#xD;
      The two devices have identical appearance and will be assigned in a double-blind fashion.&#xD;
      Study products will be provided for a total of 6-months (intervention phase); the&#xD;
      intervention phase will be followed by a further 6-months observational period (follow-up&#xD;
      phase) during which no products will be dispensed to participants. Throughout the follow-up&#xD;
      phase and up to the final visit at 12-months, changes in smoking/vaping behavior and in their&#xD;
      pattern of use will be tracked under naturalistic condition and compared between study&#xD;
      groups. Any changes in symptom severity related to schizophrenia spectrum disorders within&#xD;
      and between both arms of the study will be monitored. The intervention phase of the study&#xD;
      will consist of a total of nine visits (including screening). The follow-up phase will&#xD;
      consist of three additional visits (two telephone contacts and one final face to face visit).&#xD;
&#xD;
      In summary, the main objectives of the study will be to:&#xD;
&#xD;
        1. Quantify the proportion of continuous quitters among participants at 6-months in both&#xD;
           arms of the study;&#xD;
&#xD;
        2. Quantify the proportion of continuous reducers among participants at 6-months in both&#xD;
           arms of the study;&#xD;
&#xD;
        3. Quantify the proportion of continuous quitters among participants at 12-months in both&#xD;
           arms of the study;&#xD;
&#xD;
        4. Quantify the proportion of continuous reducers among participants at 12-months in both&#xD;
           arms of the study;&#xD;
&#xD;
        5. Compare continuous quit and reduction rates between study arms at 6- and 12-months;&#xD;
&#xD;
        6. Quantify adverse events throughout the whole duration of the interventional phase of the&#xD;
           study in both arms;&#xD;
&#xD;
        7. Compare adverse events between study arms.&#xD;
&#xD;
      Additional objectives of the study will be to:&#xD;
&#xD;
        1. Measure Subjective perceptions and experiences of the two nicotine strenghts by the&#xD;
           psychometrically validated modified Cigarette Evaluation Questionnaire - mCEQ (at&#xD;
           6-months);&#xD;
&#xD;
        2. Compare level of mCEQ between study arms (at 6-months);&#xD;
&#xD;
        3. Assess pattern of products use among participants throughout the whole duration of the&#xD;
           study (both at intervention + follow-up phases) in both arms of the study;&#xD;
&#xD;
        4. Compare pattern of product use between study arms (both at intervention + follow-up&#xD;
           phases).&#xD;
&#xD;
        5. Compare changes in symptom severity of patients with schizophrenia by Positive and&#xD;
           Negative Syndrome Scale (PANSS) within and between both arms of the study (both at 6-&#xD;
           and 12-months);&#xD;
&#xD;
        6. Compare changes in exercise tolerance by Chester Step Test within and between both arms&#xD;
           of the study (only at 6-months);&#xD;
&#xD;
        7. Compare changes in weight/BMI within and between both arms of the study (both at 6- and&#xD;
           12-months);&#xD;
&#xD;
        8. Quantify self-rated mental health (SRMH) throughout the whole duration of the study (by&#xD;
           means of a specifically designed APP) within and between both arms of the study (both at&#xD;
           6- and 12-months).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 30, 2021</start_date>
  <completion_date type="Anticipated">February 2023</completion_date>
  <primary_completion_date type="Anticipated">November 2022</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rates of participants with continuous smoking abstinence at 6-month</measure>
    <time_frame>24 WEEK</time_frame>
    <description>self-reported continuous smoking abstinence at 6-month from the previous visit, biochemically verified by exhaled CO measurements of ≤ 7 ppm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rates of participants with continuous smoking abstinence at 12-month</measure>
    <time_frame>52 WEEK</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of participants with continuous smoking reduction at 6-month</measure>
    <time_frame>24 WEEK</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rates of participants with continuous smoking reduction at 12-month</measure>
    <time_frame>52 WEEK</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of AEs</measure>
    <time_frame>24 WEEK</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute change in PANSS</measure>
    <time_frame>24 WEEK</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute change in mCEQ</measure>
    <time_frame>24 WEEK</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute change in Chester Step Test-derived values</measure>
    <time_frame>24 WEEK</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in App-derived endpoints (self-rated mental health -SRMH).</measure>
    <time_frame>24 WEEK</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">260</enrollment>
  <condition>Smoking</condition>
  <condition>Schizophrenia Spectrum and Other Psychotic Disorders</condition>
  <arm_group>
    <arm_group_label>HIGH 5%</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>LOW 1.7%</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>JUUL E-CIGARETTE</intervention_name>
    <description>JUUL E-CIGARETTE USAGE FOR 24 WEEKS</description>
    <arm_group_label>HIGH 5%</arm_group_label>
    <arm_group_label>LOW 1.7%</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult (&gt;18yrs)&#xD;
&#xD;
          -  Regular smoking (&gt;10 cigarettes a day; for at least one year)&#xD;
&#xD;
          -  Exhaled breath CO (eCO) level &gt; 7 ppm&#xD;
&#xD;
          -  Not currently attempting to quit smoking or wishing to do so in the next 30 days; this&#xD;
             will be verified at screening by the answer ''NO'' to the question ''Do you intend to&#xD;
             quit in the next 30 days?''&#xD;
&#xD;
          -  Schizophrenia spectrum disorder diagnosis (schizophrenia, delusional disorder,&#xD;
             schizoaffective disorder, personality disorder, schizoid personality disorder, etc) by&#xD;
             DSM-V criteria&#xD;
&#xD;
          -  Understand and provide informed consent&#xD;
&#xD;
          -  Able to comply with all study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Institutionalized patients&#xD;
&#xD;
          -  Acute decompensation of Schizophrenia spectrum disorder symptoms within the past month&#xD;
&#xD;
          -  Change in antipsychotic treatment within the past month&#xD;
&#xD;
          -  No recent history of hospitalization for any serious medical condition within 3 months&#xD;
             prior to screening, as determined by the investigator.&#xD;
&#xD;
          -  Myocardial infarction or angina pectoris within 3 months prior to screening, as&#xD;
             determined by the investigator.&#xD;
&#xD;
          -  Current poorly controlled asthma or COPD&#xD;
&#xD;
          -  Pregnancy, planned pregnancy or breastfeeding. Any female participant who becomes&#xD;
             pregnant during this study will be withdrawn.&#xD;
&#xD;
          -  Participants who have a significant history of alcoholism or drug/chemical abuse&#xD;
             within 12 months prior to screening, as determined by the investigator.&#xD;
&#xD;
          -  Accepting to take part in a smoking cessation program&#xD;
&#xD;
          -  Participants who regularly use any recreational nicotine (e.g. e-cigarettes,) or&#xD;
             tobacco product (e.g. tobacco heated products, oral smokeless) other than their own&#xD;
             cigarettes within 30 days of screening.&#xD;
&#xD;
          -  Participants who have used smoking cessation therapies (e.g varenecline, buproprion,&#xD;
             or NRT) within 30 days of screening.&#xD;
&#xD;
          -  Participants who are still participating in another clinical study (e.g. attending&#xD;
             follow-up visits) or who have recently participated in a clinical study involving&#xD;
             administration of an investigational drug (new chemical entity) within the past 3&#xD;
             months.&#xD;
&#xD;
          -  Participants who have, or who have a history of, any clinically-significant&#xD;
             neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric,&#xD;
             respiratory, metabolic, endocrine, haematological or other major disorder that, in the&#xD;
             opinion of the investigator or their appropriately qualified designee, would&#xD;
             jeopardise the safety of the participant or impact on the validity of the study&#xD;
             results.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pasquale Caponnetto</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Catania</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>PASQUALE CAPONNETTO, PhD</last_name>
    <phone>00390953781537</phone>
    <email>p.caponnetto@unict.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>CPCT</name>
      <address>
        <city>Catania</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pasquale Caponnetto</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>May 16, 2022</last_update_submitted>
  <last_update_submitted_qc>May 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Catania</investigator_affiliation>
    <investigator_full_name>PASQUALE CAPONNETTO</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
    <mesh_term>Schizophrenia Spectrum and Other Psychotic Disorders</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/NCT04452175
org study id: GENESIS, RCT UKRIT
nct id: NCT04452175
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Smokers with schizophrenia spectrum disorders have high rates of morbidity and mortality from
      smoking-related diseases compared with the general population and current options for smoking
      cessation in this vulnerable group are unsatisfactory.

      Considering that most people with schizophrenia spectrum disorders continue smoking, it is
      urgent to consider alternative and more efficient interventions to reduce or prevent their
      morbidity and mortality. Switching to combustion-free technologies for nicotine delivery
      (I.e. e-cigarettes) could be a pragmatic and much less harmful alternative to tobacco smoking
      with the possibility of significant health gains. Emerging research is suggesting that ECs
      may be useful for smoking cessation and relapse prevention in people with schizophrenia
      spectrum disorders. In particular, a study conducted with JUUL e-cigarette with 5% nicotine
      strength showed that this product had sufficient nicotine delivery and product appeal to
      determine high success rates in heavy smokers with schizophrenia spectrum disorders.

      In consideration of these preliminary findings, we hypothesized that switching smokers with a
      schizophrenia spectrum disorder diagnosis to JUUL e-cigarette with 5% nicotine strength could
      result in higher success rates compared to JUUL e-cigarette with 1.7% nicotine strength.
      Recent work indicates that nicotine PK of the JUUL e-cigarette with 5% nicotine strength (a
      device that utilizes a nicotine salt formulation) approximates the nicotine delivery of
      combustible cigarettes and that the 5% nicotine strength product is far more efficient in
      delivering nicotine compared to the sister product with 1.7% nicotine strength. Both products
      are identical in their appearance, making them suitable for a double-blind study design.
Multicenter, 12-months prospective trial, utilizing a randomized, double-blind, 2-arm
      parallel, switching design to compare effectiveness, tolerability, acceptability, and pattern
      of use between high (JUUL 5% nicotine) and low nicotine strength devices (JUUL 1.7% nicotine)
      in adult smokers with schizophrenia spectrum disorders. The study will take place at 5
      international sites: UK (London), Italy (Catania), Russia (Ufa and St. Petersburg) and
      Ukraine (Kiev).

      The two devices have identical appearance and will be assigned in a double-blind fashion.
      Study products will be provided for a total of 6-months (intervention phase); the
      intervention phase will be followed by a further 6-months observational period (follow-up
      phase) during which no products will be dispensed to participants. Throughout the follow-up
      phase and up to the final visit at 12-months, changes in smoking/vaping behavior and in their
      pattern of use will be tracked under naturalistic condition and compared between study
      groups. Any changes in symptom severity related to schizophrenia spectrum disorders within
      and between both arms of the study will be monitored. The intervention phase of the study
      will consist of a total of nine visits (including screening). The follow-up phase will
      consist of three additional visits (two telephone contacts and one final face to face visit).

      In summary, the main objectives of the study will be to:

        1. Quantify the proportion of continuous quitters among participants at 6-months in both
           arms of the study;

        2. Quantify the proportion of continuous reducers among participants at 6-months in both
           arms of the study;

        3. Quantify the proportion of continuous quitters among participants at 12-months in both
           arms of the study;

        4. Quantify the proportion of continuous reducers among participants at 12-months in both
           arms of the study;

        5. Compare continuous quit and reduction rates between study arms at 6- and 12-months;

        6. Quantify adverse events throughout the whole duration of the interventional phase of the
           study in both arms;

        7. Compare adverse events between study arms.

      Additional objectives of the study will be to:

        1. Measure Subjective perceptions and experiences of the two nicotine strenghts by the
           psychometrically validated modified Cigarette Evaluation Questionnaire - mCEQ (at
           6-months);

        2. Compare level of mCEQ between study arms (at 6-months);

        3. Assess pattern of products use among participants throughout the whole duration of the
           study (both at intervention + follow-up phases) in both arms of the study;

        4. Compare pattern of product use between study arms (both at intervention + follow-up
           phases).

        5. Compare changes in symptom severity of patients with schizophrenia by Positive and
           Negative Syndrome Scale (PANSS) within and between both arms of the study (both at 6-
           and 12-months);

        6. Compare changes in exercise tolerance by Chester Step Test within and between both arms
           of the study (only at 6-months);

        7. Compare changes in weight/BMI within and between both arms of the study (both at 6- and
           12-months);

        8. Quantify self-rated mental health (SRMH) throughout the whole duration of the study (by
           means of a specifically designed APP) within and between both arms of the study (both at
           6- and 12-months).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Rates of participants with continuous smoking abstinence at 6-month
time frame: 24 WEEK
description: self-reported continuous smoking abstinence at 6-month from the previous visit, biochemically verified by exhaled CO measurements of ≤ 7 ppm
measure: Rates of participants with continuous smoking abstinence at 12-month
time frame: 52 WEEK
measure: Rates of participants with continuous smoking reduction at 6-month
time frame: 24 WEEK
measure: Rates of participants with continuous smoking reduction at 12-month
time frame: 52 WEEK
measure: Proportion of AEs
time frame: 24 WEEK
measure: Absolute change in PANSS
time frame: 24 WEEK
measure: Absolute change in mCEQ
time frame: 24 WEEK
measure: Absolute change in Chester Step Test-derived values
time frame: 24 WEEK
measure: Change in App-derived endpoints (self-rated mental health -SRMH).
time frame: 24 WEEK
arm group label: HIGH 5%
arm group type: Experimental
arm group label: LOW 1.7%
arm group type: Active Comparator
intervention type: Other
intervention name: JUUL E-CIGARETTE
description: JUUL E-CIGARETTE USAGE FOR 24 WEEKS
arm group label: HIGH 5%
arm group label: LOW 1.7%
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pasquale Caponnetto
role: Principal Investigator
affiliation: University of Catania
last name: PASQUALE CAPONNETTO, PhD
phone: 00390953781537
email: p.caponnetto@unict.it
facility: 
status: Recruiting
contact: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Catania
investigator full name: PASQUALE CAPONNETTO
investigator title: Principal Investigator
mesh term: Schizophrenia
mesh term: Psychotic Disorders
mesh term: Schizophrenia Spectrum and Other Psychotic Disorders