<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/NCT04490057</url>
  </required_header>
  <id_info>
    <org_study_id>2000026332</org_study_id>
    <secondary_id>R01CA243910</secondary_id>
    <nct_id>NCT04490057</nct_id>
  </id_info>
  <brief_title>A Smart Approach to Treating Tobacco Use Disorder in Persons Living With HIV</brief_title>
  <acronym>SMARTTT</acronym>
  <official_title>A Smart Approach to Treating Tobacco Use Disorder in Persons Living With HIV</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Many people living with HIV (PLWH) smoke. Smoking in these individuals is often undertreated.&#xD;
      This study plans to assess the ability of various clinical pathways involving tobacco&#xD;
      treatment medications and contingency management (paying smokers for not smoking) to improve&#xD;
      smoking cessation in a group of PLWH.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Using a Sequential Multiple Assignment Randomized Trial (SMART) design, this project is a&#xD;
      two-arm, two-stage randomized trial of 632 adult PWH who smoke cigarettes and receive care in&#xD;
      one of three health systems. At inception, participants will be randomized to either&#xD;
      combination nicotine replacement therapy (NRT, patch + short-acting NRT) or combination&#xD;
      NRT+contingency management (CM). At 12 weeks, responders (non-smoking participants confirmed&#xD;
      by exhaled carbon monoxide [eCO]) in both arms will receive 12 more weeks of the same&#xD;
      treatment. Non-responders (participants with continued smoking by self-report and/or eCO) in&#xD;
      both the NRT and NRT+CM arms will be re-randomized to 12 weeks of treatment, either with&#xD;
      medication switch to oral medication, varenicline or bupropion, or intensified level of CM&#xD;
      (start CM if no CM during first 12 weeks, or CM with higher reward schedule [&quot;CM plus&quot;] if&#xD;
      NRT+CM group initially). The intervention will be delivered by trained clinical pharmacists.&#xD;
      The primary outcome will be eCO-confirmed abstinence at 24 weeks post-enrollment. The&#xD;
      specific aims of the proposed study are to: (1) identify the optimal adaptive approach to&#xD;
      promote eCO-confirmed smoking abstinence (2) study the effectiveness of various adaptive&#xD;
      strategies on CD4 count, HIV viral suppression, and VACS index (validated measure of&#xD;
      morbidity and mortality risk); and (3) grounded in implementation science and using aHybrid&#xD;
      Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering&#xD;
      our intervention to inform future implementation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 27, 2020</start_date>
  <completion_date type="Anticipated">August 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2024</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Sequential multiple assignment randomized trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Self reported reduction in average cigarettes smoked per day at 24 weeks</measure>
    <time_frame>24 weeks from baseline</time_frame>
    <description>Self reported reduction in average cigarettes smoked per day</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Self reported reduction in average cigarettes smoked per day at 12 weeks</measure>
    <time_frame>12 weeks from baseline</time_frame>
    <description>Self reported reduction in average cigarettes smoked per day</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>VACS index 2.0</measure>
    <time_frame>24 weeks from baseline</time_frame>
    <description>A validated measure of morbidity and mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD4 Count</measure>
    <time_frame>24 weeks from baseline</time_frame>
    <description>Median CD4 count adjusting for baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HIV Viral Load</measure>
    <time_frame>24 weeks from baseline</time_frame>
    <description>The proportion of participants with HIV viral load suppression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eCO confirmed smoking abstinence at 24 weeks</measure>
    <time_frame>24 weeks from baseline</time_frame>
    <description>smoking abstinence confirmed by exhaled carbon monoxide</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eCO confirmed smoking abstinence at 12 weeks</measure>
    <time_frame>12 weeks from baseline</time_frame>
    <description>smoking abstinence confirmed by exhaled carbon monoxide</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Identification of Barriers and Facilitators</measure>
    <time_frame>Baseline and Up to 4 years</time_frame>
    <description>Using a Hybrid Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering our intervention to inform future implementation.</description>
  </other_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">632</enrollment>
  <condition>Tobacco Use Cessation</condition>
  <arm_group>
    <arm_group_label>12 wks NRT+CM / 12 wks NRT+CM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine replacement therapy combined with contingency management. Responders remain on same treatment for second 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>12 wks NRT+CM/ 12 wks VAR or bupropion+CM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine replacement therapy combined with contingency management. Non-responders switch to varenicline or bupropion combined with contingency management for second 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>12 wks NRT+CM/12 wks NRT+CM plus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine replacement therapy combined with contingency management Non-responders switch to nicotine replacement therapy combined with intensified contingency management for second 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>12 wks NRT/ 12 wks NRT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine replacement therapy alone. Responders remain on nicotine replacement therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>12 wks NRT/ 12 wks VAR or bupropion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine replacement therapy alone. Non-responders switch to varenicline or bupropion alone for second 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>12 wks NRT/ 12 wks NRT+CM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine replacement therapy alone. Non-responders switch to nicotine replacement therapy combined with contingency management for second 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler</intervention_name>
    <description>Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.</description>
    <arm_group_label>12 wks NRT+CM / 12 wks NRT+CM</arm_group_label>
    <arm_group_label>12 wks NRT+CM/ 12 wks VAR or bupropion+CM</arm_group_label>
    <arm_group_label>12 wks NRT+CM/12 wks NRT+CM plus</arm_group_label>
    <arm_group_label>12 wks NRT/ 12 wks NRT</arm_group_label>
    <arm_group_label>12 wks NRT/ 12 wks NRT+CM</arm_group_label>
    <arm_group_label>12 wks NRT/ 12 wks VAR or bupropion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varenicline or bupropion</intervention_name>
    <description>Participants will be prescribed varenicline (Chantix) or bupropion (Wellbutrin).</description>
    <arm_group_label>12 wks NRT+CM/ 12 wks VAR or bupropion+CM</arm_group_label>
    <arm_group_label>12 wks NRT/ 12 wks VAR or bupropion</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Contingency Management</intervention_name>
    <description>Participants will be financially rewarded for abstinence to tobacco.</description>
    <arm_group_label>12 wks NRT+CM / 12 wks NRT+CM</arm_group_label>
    <arm_group_label>12 wks NRT+CM/ 12 wks VAR or bupropion+CM</arm_group_label>
    <arm_group_label>12 wks NRT+CM/12 wks NRT+CM plus</arm_group_label>
    <arm_group_label>12 wks NRT/ 12 wks NRT+CM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV positive;&#xD;
&#xD;
          -  &gt;= 18 years old&#xD;
&#xD;
          -  Receiving HIV care at Yale-New Haven Hospital, Mount Sinai Hospital, or SUNY Downstate&#xD;
             STAR clinic;&#xD;
&#xD;
          -  Have smoked &gt;= 100 cigarettes in lifetime;&#xD;
&#xD;
          -  Currently smokes some days or every day;&#xD;
&#xD;
          -  Smokes, on average, &gt;= 5 cigarettes per day;&#xD;
&#xD;
          -  Able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Using only non-cigarette nicotine products (i.e., e-cigs, Juul, etc.);&#xD;
&#xD;
          -  Currently using NRT, VAR, or bupropion (defined as use in the prior 7 days);&#xD;
&#xD;
          -  Self-report or urine testing confirming pregnancy, nursing, or trying to conceive;&#xD;
&#xD;
          -  Life-threatening or unstable medical, surgical, or psychiatric condition;&#xD;
&#xD;
          -  Inability to provide at least one collateral contact (family member or friend);&#xD;
&#xD;
          -  Living out of state;&#xD;
&#xD;
          -  Unable to read or understand English (except at Mount Sinai site).&#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>E. Jennifer Edelman, MD, MHS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steven Bernstein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dartmouth College</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>June-Marie Weiss, MA, MEd</last_name>
    <phone>203-737-3347</phone>
    <email>junemarie.weiss@yale.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>E. Jennifer Edelman, MD, MHS</last_name>
      <phone>203-737-7115</phone>
      <email>ejennifer.edelman@yale.edu</email>
    </contact>
    <contact_backup>
      <last_name>June-Marie Weiss, MA, MEd</last_name>
      <phone>203-737-3347</phone>
      <email>junemarie.weiss@yale.edu</email>
    </contact_backup>
    <investigator>
      <last_name>E. Jennifer Edelman, MD, MHS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>SUNY Downstate STAR Clinic</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jessica Yager, MD</last_name>
      <email>jessica.yager@downstate.edu</email>
    </contact>
    <contact_backup>
      <last_name>Mayange Frederick</last_name>
      <phone>718-270-8641</phone>
      <email>mayange.frederick@downstate.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Jessica Yager, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Keith Sigel, MD</last_name>
      <email>keith.sigel@mssm.edu</email>
    </contact>
    <contact_backup>
      <last_name>Elisa McBratney</last_name>
      <phone>212-824-7455</phone>
      <email>elisa.mcbratney@mountsinai.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>June 23, 2023</last_update_submitted>
  <last_update_submitted_qc>June 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bupropion</mesh_term>
    <mesh_term>Nicotine</mesh_term>
    <mesh_term>Varenicline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT04490057/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04490057
org study id: 2000026332
secondary id: R01CA243910
nct id: NCT04490057
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Many people living with HIV (PLWH) smoke. Smoking in these individuals is often undertreated.
      This study plans to assess the ability of various clinical pathways involving tobacco
      treatment medications and contingency management (paying smokers for not smoking) to improve
      smoking cessation in a group of PLWH.
Using a Sequential Multiple Assignment Randomized Trial (SMART) design, this project is a
      two-arm, two-stage randomized trial of 632 adult PWH who smoke cigarettes and receive care in
      one of three health systems. At inception, participants will be randomized to either
      combination nicotine replacement therapy (NRT, patch + short-acting NRT) or combination
      NRT+contingency management (CM). At 12 weeks, responders (non-smoking participants confirmed
      by exhaled carbon monoxide [eCO]) in both arms will receive 12 more weeks of the same
      treatment. Non-responders (participants with continued smoking by self-report and/or eCO) in
      both the NRT and NRT+CM arms will be re-randomized to 12 weeks of treatment, either with
      medication switch to oral medication, varenicline or bupropion, or intensified level of CM
      (start CM if no CM during first 12 weeks, or CM with higher reward schedule ["CM plus"] if
      NRT+CM group initially). The intervention will be delivered by trained clinical pharmacists.
      The primary outcome will be eCO-confirmed abstinence at 24 weeks post-enrollment. The
      specific aims of the proposed study are to: (1) identify the optimal adaptive approach to
      promote eCO-confirmed smoking abstinence (2) study the effectiveness of various adaptive
      strategies on CD4 count, HIV viral suppression, and VACS index (validated measure of
      morbidity and mortality risk); and (3) grounded in implementation science and using aHybrid
      Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering
      our intervention to inform future implementation.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Sequential multiple assignment randomized trial
primary purpose: Treatment
masking: None (Open Label)
measure: Self reported reduction in average cigarettes smoked per day at 24 weeks
time frame: 24 weeks from baseline
description: Self reported reduction in average cigarettes smoked per day
measure: Self reported reduction in average cigarettes smoked per day at 12 weeks
time frame: 12 weeks from baseline
description: Self reported reduction in average cigarettes smoked per day
measure: VACS index 2.0
time frame: 24 weeks from baseline
description: A validated measure of morbidity and mortality
measure: CD4 Count
time frame: 24 weeks from baseline
description: Median CD4 count adjusting for baseline
measure: HIV Viral Load
time frame: 24 weeks from baseline
description: The proportion of participants with HIV viral load suppression.
measure: eCO confirmed smoking abstinence at 24 weeks
time frame: 24 weeks from baseline
description: smoking abstinence confirmed by exhaled carbon monoxide
measure: eCO confirmed smoking abstinence at 12 weeks
time frame: 12 weeks from baseline
description: smoking abstinence confirmed by exhaled carbon monoxide
measure: Identification of Barriers and Facilitators
time frame: Baseline and Up to 4 years
description: Using a Hybrid Effectiveness-Implementation Type I design, identify barriers and facilitators to delivering our intervention to inform future implementation.
arm group label: 12 wks NRT+CM / 12 wks NRT+CM
arm group type: Experimental
description: Nicotine replacement therapy combined with contingency management. Responders remain on same treatment for second 12 weeks.
arm group label: 12 wks NRT+CM/ 12 wks VAR or bupropion+CM
arm group type: Experimental
description: Nicotine replacement therapy combined with contingency management. Non-responders switch to varenicline or bupropion combined with contingency management for second 12 weeks.
arm group label: 12 wks NRT+CM/12 wks NRT+CM plus
arm group type: Experimental
description: Nicotine replacement therapy combined with contingency management Non-responders switch to nicotine replacement therapy combined with intensified contingency management for second 12 weeks.
arm group label: 12 wks NRT/ 12 wks NRT
arm group type: Experimental
description: Nicotine replacement therapy alone. Responders remain on nicotine replacement therapy.
arm group label: 12 wks NRT/ 12 wks VAR or bupropion
arm group type: Experimental
description: Nicotine replacement therapy alone. Non-responders switch to varenicline or bupropion alone for second 12 weeks.
arm group label: 12 wks NRT/ 12 wks NRT+CM
arm group type: Experimental
description: Nicotine replacement therapy alone. Non-responders switch to nicotine replacement therapy combined with contingency management for second 12 weeks.
intervention type: Drug
intervention name: Nicotine patch, nicotine gum, nicotine nasal spray, nicotine inhaler
description: Participants will be prescribed both long-acting and short-acting nicotine replacement therapy.
arm group label: 12 wks NRT+CM / 12 wks NRT+CM
arm group label: 12 wks NRT+CM/ 12 wks VAR or bupropion+CM
arm group label: 12 wks NRT+CM/12 wks NRT+CM plus
arm group label: 12 wks NRT/ 12 wks NRT
arm group label: 12 wks NRT/ 12 wks NRT+CM
arm group label: 12 wks NRT/ 12 wks VAR or bupropion
intervention type: Drug
intervention name: Varenicline or bupropion
description: Participants will be prescribed varenicline (Chantix) or bupropion (Wellbutrin).
arm group label: 12 wks NRT+CM/ 12 wks VAR or bupropion+CM
arm group label: 12 wks NRT/ 12 wks VAR or bupropion
intervention type: Behavioral
intervention name: Contingency Management
description: Participants will be financially rewarded for abstinence to tobacco.
arm group label: 12 wks NRT+CM / 12 wks NRT+CM
arm group label: 12 wks NRT+CM/ 12 wks VAR or bupropion+CM
arm group label: 12 wks NRT+CM/12 wks NRT+CM plus
arm group label: 12 wks NRT/ 12 wks NRT+CM
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: E. Jennifer Edelman, MD, MHS
role: Principal Investigator
affiliation: Yale University
last name: Steven Bernstein, MD
role: Principal Investigator
affiliation: Dartmouth College
last name: June-Marie Weiss, MA, MEd
phone: 203-737-3347
email: junemarie.weiss@yale.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
mesh term: Bupropion
mesh term: Nicotine
mesh term: Varenicline
sharing ipd: No
provided document: 