<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/NCT03841292</url>
  </required_header>
  <id_info>
    <org_study_id>REB #044/2016</org_study_id>
    <nct_id>NCT03841292</nct_id>
  </id_info>
  <brief_title>Using Non-invasive Brain Stimulation (tDCS) With Varenicline for Treating Tobacco Dependence</brief_title>
  <official_title>Using Non-invasive Brain Stimulation (tDCS) to Improve the Effectiveness of Varenicline for Treating Tobacco Dependence: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre for Addiction and Mental Health</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The addition of tDCS as an adjunct to pharmacotherapy is a novel approach but one that is&#xD;
      grounded in a growing evidence-base.The primary objective of this research is to provide&#xD;
      preliminary evidence of the effectiveness of tDCS as an adjunct treatment to pharmacotherapy&#xD;
      for smoking cessation. The investigators hypothesize that the addition of active tDCS to the&#xD;
      left DLPFC will improve the effectiveness of varenicline as reflected by higher quit rates at&#xD;
      end of treatment compared to the sham group. Smoking status will be biochemically confirmed&#xD;
      at various time points using expired cotinine measures. Furthermore, the investigators will&#xD;
      be collecting neuroimaging (fMRI) data as well as measures of attentional bias to explore the&#xD;
      neurological and physiological correlates from using adjunct tDCS and varenicline therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      While varenicline on its own is the most effective medication for smoking cessation,&#xD;
      long-term abstinence is still relatively poor. The primary objective of this study is to&#xD;
      evaluate the effectiveness of adjunct active tDCS with varenicline in treating tobacco&#xD;
      dependence. This study is a double-blind, sham-controlled, randomized clinical trial where 50&#xD;
      daily dependent treatment seeking smokers will be recruited at the Nicotine Dependence Clinic&#xD;
      in Toronto, Canada. Participants will be receiving twelve weeks of varenicline treatment (1mg&#xD;
      b.i.d.) and randomized 1:1 to either active tDCS (active: 20 minutes at 2 mA) or sham tDCS&#xD;
      (30 seconds at 2 mA, 19.5 minutes at 0 mA), daily (M-F) for the first 2 weeks and then every&#xD;
      2 weeks for the next 10 weeks. There will be 2 fMRI scans at baseline and 1 scan at&#xD;
      end-of-treatment. Eye-tracking viewing tests will be conducted at baseline, weeks 4, 8, 12&#xD;
      and at 6 months follow up. During the 6 month follow-up, participants will be answering&#xD;
      questions regarding their smoking behaviour and craving. Smoking status will be biochemically&#xD;
      confirmed at each study visit using expired cotinine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2018</start_date>
  <completion_date type="Actual">January 31, 2022</completion_date>
  <primary_completion_date type="Actual">January 31, 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>
    <intervention_model_description>Sham Controlled Randomized Trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double-Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in smoking status over time</measure>
    <time_frame>At weeks 12 and 26 following start of treatment</time_frame>
    <description>30 Day Continuous abstinence confirmed by expired CO &lt;/= 4 ppm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in functional brain activation during cognitive tasks</measure>
    <time_frame>At baseline and 12 weeks following start of treatment</time_frame>
    <description>change in fMRI BOLD response in the brain in response to smoking cues or when anticipating a monetary reward</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in preference of attention towards visual cues</measure>
    <time_frame>At weeks 4,8, 12 and 26 weeks following start of treatment.</time_frame>
    <description>Attentional bias to smoking cues, negative/positive cues and high-risk cues measured using an automated eye-tracking apparatus</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in brain neurocircuitry over time</measure>
    <time_frame>At baseline and 12 weeks following start of treatment</time_frame>
    <description>Differences in water diffusion in the brain when participants are at rest in a MRI scanner.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in dynamic functional connectivity of the brain at rest over time</measure>
    <time_frame>At baseline and 12 weeks following start of treatment</time_frame>
    <description>Related to differences in resting state functional brain networks when participants are not doing an explicit task in a fMRI scanner.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Tobacco Dependence</condition>
  <condition>Smoking Cessation</condition>
  <condition>Tobacco Smoking</condition>
  <condition>Tobacco Use Disorder</condition>
  <condition>Substance Use Disorders</condition>
  <condition>Molecular Mechanisms of Pharmacological Action</condition>
  <condition>Physiological Effects of Drugs</condition>
  <arm_group>
    <arm_group_label>Active tDCS+Varenicline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Active 2mA tDCS (Nuraleve, Canada) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session. Daily stimulation between Monday to Friday for the first two weeks and then booster sessions every other week for the next 10 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham tDCS+Varenicline</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham tDCS (Nuraleve, Canada)(30 seconds of 2mA and 19.5 minutes of 0 mA) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session. Daily stimulation between Monday to Friday for the first two weeks and then booster sessions every other week for the next 10 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varenicline</intervention_name>
    <description>Varenicline (Champix®), Pfizer Canada Inc., Kirkland, Quebec. Dispense for 12 weeks. One tablet (0.5mg) once daily for first three days, then one tablet (0.5 mg) twice daily for next four days, then 1 mg (one 1mg tablet) twice daily for the remainder of 12 weeks. Dose adjustments due to adverse events will be allowed (i.e. decrease to 0.5 mg twice daily).</description>
    <arm_group_label>Active tDCS+Varenicline</arm_group_label>
    <arm_group_label>Sham tDCS+Varenicline</arm_group_label>
    <other_name>Champix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active tDCS</intervention_name>
    <description>Active 2mA tDCS (Nuraleve, Canada) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session</description>
    <arm_group_label>Active tDCS+Varenicline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham tDCS</intervention_name>
    <description>Shame tDCS (Nuraleve, Canada) (30 seconds of 2mA and 19.5 minutes of 0 mA) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session.</description>
    <arm_group_label>Sham tDCS+Varenicline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or Female&#xD;
&#xD;
          -  Aged 19-65&#xD;
&#xD;
          -  Treatment seeking smoker&#xD;
&#xD;
          -  Daily smoker of CPD&gt;8&#xD;
&#xD;
          -  Able to attend daily appointments for tDCS for the first 2 weeks and booster sessions&#xD;
             for the next 10 weeks.&#xD;
&#xD;
          -  Wiling to undergo 3 fMRI sessions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current/recent DSM-IV Axis I diagnosis&#xD;
&#xD;
          -  Current use of psychoactive drugs or medications&#xD;
&#xD;
          -  History of seizures/epilepsy&#xD;
&#xD;
          -  Current use of NRT, e-cigarettes or other medications for smoking cessation&#xD;
&#xD;
          -  Metal embedded in skull or implanted electrical devices&#xD;
&#xD;
          -  No head injury (concussion or loss of consciousness for more than an hour)&#xD;
&#xD;
          -  Contraindications to fMRI&#xD;
&#xD;
          -  Contraindications to varenicline&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Laurie A Zawertailo, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for Addiction and Mental Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T1P7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>March 14, 2022</last_update_submitted>
  <last_update_submitted_qc>March 14, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for Addiction and Mental Health</investigator_affiliation>
    <investigator_full_name>Laurie Zawertailo</investigator_full_name>
    <investigator_title>Senior Scientist</investigator_title>
  </responsible_party>
  <keyword>Smoking Cessation Medication</keyword>
  <keyword>Smoking Treatment</keyword>
  <keyword>Tobacco Treatment</keyword>
  <keyword>Quitting Smoking</keyword>
  <keyword>Varenicline</keyword>
  <keyword>Transcranial Direct Current Stimulation</keyword>
  <keyword>Neuroimaging</keyword>
  <keyword>fMRI</keyword>
  <keyword>Attentional Bias</keyword>
  <keyword>Eye-tracking</keyword>
  <keyword>Dependence</keyword>
  <keyword>Addiction</keyword>
  <keyword>Cigarettes</keyword>
  <keyword>Biochemical Confirmation</keyword>
  <keyword>Cue reactivity</keyword>
  <keyword>Reward Anticipation</keyword>
  <keyword>Diffusion Tensor Imaging</keyword>
  <keyword>Resting State Functional Connectivity</keyword>
  <keyword>BOLD fMRI</keyword>
  <keyword>Quantitative T1</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Substance-Related Disorders</mesh_term>
    <mesh_term>Tobacco Use Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Varenicline</mesh_term>
  </intervention_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/NCT03841292
org study id: REB #044/2016
nct id: NCT03841292
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The addition of tDCS as an adjunct to pharmacotherapy is a novel approach but one that is
      grounded in a growing evidence-base.The primary objective of this research is to provide
      preliminary evidence of the effectiveness of tDCS as an adjunct treatment to pharmacotherapy
      for smoking cessation. The investigators hypothesize that the addition of active tDCS to the
      left DLPFC will improve the effectiveness of varenicline as reflected by higher quit rates at
      end of treatment compared to the sham group. Smoking status will be biochemically confirmed
      at various time points using expired cotinine measures. Furthermore, the investigators will
      be collecting neuroimaging (fMRI) data as well as measures of attentional bias to explore the
      neurological and physiological correlates from using adjunct tDCS and varenicline therapy.
While varenicline on its own is the most effective medication for smoking cessation,
      long-term abstinence is still relatively poor. The primary objective of this study is to
      evaluate the effectiveness of adjunct active tDCS with varenicline in treating tobacco
      dependence. This study is a double-blind, sham-controlled, randomized clinical trial where 50
      daily dependent treatment seeking smokers will be recruited at the Nicotine Dependence Clinic
      in Toronto, Canada. Participants will be receiving twelve weeks of varenicline treatment (1mg
      b.i.d.) and randomized 1:1 to either active tDCS (active: 20 minutes at 2 mA) or sham tDCS
      (30 seconds at 2 mA, 19.5 minutes at 0 mA), daily (M-F) for the first 2 weeks and then every
      2 weeks for the next 10 weeks. There will be 2 fMRI scans at baseline and 1 scan at
      end-of-treatment. Eye-tracking viewing tests will be conducted at baseline, weeks 4, 8, 12
      and at 6 months follow up. During the 6 month follow-up, participants will be answering
      questions regarding their smoking behaviour and craving. Smoking status will be biochemically
      confirmed at each study visit using expired cotinine.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Sham Controlled Randomized Trial
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double-Blind
measure: Change in smoking status over time
time frame: At weeks 12 and 26 following start of treatment
description: 30 Day Continuous abstinence confirmed by expired CO </= 4 ppm
measure: Change in functional brain activation during cognitive tasks
time frame: At baseline and 12 weeks following start of treatment
description: change in fMRI BOLD response in the brain in response to smoking cues or when anticipating a monetary reward
measure: Change in preference of attention towards visual cues
time frame: At weeks 4,8, 12 and 26 weeks following start of treatment.
description: Attentional bias to smoking cues, negative/positive cues and high-risk cues measured using an automated eye-tracking apparatus
measure: Change in brain neurocircuitry over time
time frame: At baseline and 12 weeks following start of treatment
description: Differences in water diffusion in the brain when participants are at rest in a MRI scanner.
measure: Change in dynamic functional connectivity of the brain at rest over time
time frame: At baseline and 12 weeks following start of treatment
description: Related to differences in resting state functional brain networks when participants are not doing an explicit task in a fMRI scanner.
arm group label: Active tDCS+Varenicline
arm group type: Active Comparator
description: Active 2mA tDCS (Nuraleve, Canada) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session. Daily stimulation between Monday to Friday for the first two weeks and then booster sessions every other week for the next 10 weeks.
arm group label: Sham tDCS+Varenicline
arm group type: Sham Comparator
description: Sham tDCS (Nuraleve, Canada)(30 seconds of 2mA and 19.5 minutes of 0 mA) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session. Daily stimulation between Monday to Friday for the first two weeks and then booster sessions every other week for the next 10 weeks.
intervention type: Drug
intervention name: Varenicline
description: Varenicline (Champix®), Pfizer Canada Inc., Kirkland, Quebec. Dispense for 12 weeks. One tablet (0.5mg) once daily for first three days, then one tablet (0.5 mg) twice daily for next four days, then 1 mg (one 1mg tablet) twice daily for the remainder of 12 weeks. Dose adjustments due to adverse events will be allowed (i.e. decrease to 0.5 mg twice daily).
arm group label: Active tDCS+Varenicline
arm group label: Sham tDCS+Varenicline
other name: Champix
intervention type: Device
intervention name: Active tDCS
description: Active 2mA tDCS (Nuraleve, Canada) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session
arm group label: Active tDCS+Varenicline
intervention type: Device
intervention name: Sham tDCS
description: Shame tDCS (Nuraleve, Canada) (30 seconds of 2mA and 19.5 minutes of 0 mA) with the anode placed over the left dorsolateral prefrontal cortex (dlPFC) and the cathode placed over the right dlPFC for 20 minutes per session.
arm group label: Sham tDCS+Varenicline
criteria: 
gender: All
minimum age: 19 Years
maximum age: 65 Years
healthy volunteers: No
last name: Laurie A Zawertailo, PhD
role: Principal Investigator
affiliation: Centre for Addiction and Mental Health
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Laurie Zawertailo
investigator title: Senior Scientist
mesh term: Substance-Related Disorders
mesh term: Tobacco Use Disorder
mesh term: Varenicline