<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/NCT02212405</url>
  </required_header>
  <id_info>
    <org_study_id>170/2010</org_study_id>
    <nct_id>NCT02212405</nct_id>
  </id_info>
  <brief_title>Does the Insula Control Smoking-Induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans.</brief_title>
  <official_title>Does the Insula Control Smoking-Induced Dopamine Release? A TMS/[11C]-PHNO Study in Humans (Part II).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Brainsway</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Findings from this study may demonstrate how the insula contributes to reward pathways&#xD;
      involved in addiction. There are three main hypotheses for this trial. The first is that&#xD;
      inhibiting the insula using transcranial magnetic stimulation (TMS) will not cause noticeable&#xD;
      changes of dopamine release in the striatum. The second is that stimulating the insula with&#xD;
      TMS will increase dopamine release in the striatum, and will be visualized on PET imaging as&#xD;
      decreased radiotracer binding. The third hypothesis is that the participants will not&#xD;
      experience major side effects from TMS on the insula.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This project will take advantage of the recently developed Deep rTMS coil to target the&#xD;
      insular cortex. Few studies have examined the possibility of using repetitive Transcranial&#xD;
      Magnetic Stimulation (rTMS) for nicotine addiction and none so far have explored the use of a&#xD;
      coil that specifically targets the insular region. The objective of this study is to test&#xD;
      whether low and high-frequency rTMS of the insula modulates striatal dopamine (DA) release in&#xD;
      healthy humans. Positron Emission Tomography (PET) with [11C]-(+)-PHNO, a radiotracer which&#xD;
      is very sensitive to fluctuations in DA transmission in the human brain, will be used to&#xD;
      assess the impact of rTMS on dopamine levels. This project will yield the first data in&#xD;
      humans linking the insula to the DA system in vivo. These findings could lead to the&#xD;
      identification of optimal parameters for Deep rTMS to use secondarily in a proof of principle&#xD;
      clinical study in smokers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</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>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in [11C]-(+)-PHNO binding</measure>
    <time_frame>Participants will complete all sessions in a period of approximately 4 weeks.</time_frame>
    <description>[11C]-(+)-PHNO binding at D2/3 receptors will be measured with PET imaging following rTMS at 1Hz, 10Hz, and sham stimulation. Binding at regions of interest will be compared between trial conditions.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>rTMS Sham + PET</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>An advanced sham coil will be used that mimicks the sound and sensation of real repetitive Transcranial Magnetic Stimulation. The repetitive Transcranial Magnetic Stimulation sham intervention is followed by radiotracer and PET.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rTMS 1Hz + PET</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Deep repetitive Transcranial Magnetic Stimulation will be applied to the insula for 30 minutes. This will consist of 20 trains each comprising of 50 pulses at 1Hz. The inter-train interval is 15 seconds. The intervention is followed by radiotracer and PET.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rTMS 10Hz + PET.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Deep repetitive Transcranial Magnetic Stimulation will be applied to the insula for 30 minutes. This will consist of 34 trains each comprising of 30 pulses at 10Hz. The inter-train interval is 3 seconds. The intervention is followed by radiotracer and PET.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>repetitive Transcranial Magnetic Stimulation</intervention_name>
    <description>Each participant will participate in all three arms to receive sham, 1hz and 10hz rTMS as well as PET imaging.</description>
    <arm_group_label>rTMS 10Hz + PET.</arm_group_label>
    <arm_group_label>rTMS 1Hz + PET</arm_group_label>
    <other_name>Deep Repetitive Transcranial Magnetic Stimulation</other_name>
    <other_name>DTMS HLRIADD-COIL, Model 102B</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>repetitive Transcranial Magnetic Stimulation Sham</intervention_name>
    <description>The sham coil is built in the same helmet of the active coil. The sham coil is has a circular shape and placed perpendicular to the scalp within the same helmet. This coil produces a similar sound and scalp sensation as the real coil.</description>
    <arm_group_label>rTMS Sham + PET</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male or female&#xD;
&#xD;
          -  Between the ages of 19 and 45&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Presence of metal objects in the body or implanted electronic devices, that preclude&#xD;
             safe MR scanning.&#xD;
&#xD;
          -  Claustrophobia.&#xD;
&#xD;
          -  Cardiovascular or cerebrovascular diseases.&#xD;
&#xD;
          -  Major psychiatric disorders including mood, anxiety or psychotic disorders.&#xD;
&#xD;
          -  History of or current neurological illnesses including seizure disorders, migraine,&#xD;
             multiple sclerosis, movement disorders, head trauma, CVA or CNS tumor.&#xD;
&#xD;
          -  Gross structural brain abnormalities as revealed by T1 weighted images.&#xD;
&#xD;
          -  Current use or use during the previous month of medication that may affect the CNS&#xD;
             (e.g. neuroleptics, bupropion).&#xD;
&#xD;
          -  Learning disability, amnesia or other conditions that impede memory and attention.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bernard LeFoll, M.D., Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>CAMH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5S 2S1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.camh.ca/en/research/Pages/research.aspx</url>
    <description>Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching</description>
  </link>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>July 30, 2014</study_first_submitted>
  <study_first_submitted_qc>August 6, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>August 30, 2016</last_update_submitted>
  <last_update_submitted_qc>August 30, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 1, 2016</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>Bernard Le Foll</investigator_full_name>
    <investigator_title>Principal investigator, MD, PhD, CCFP</investigator_title>
  </responsible_party>
  <keyword>Deep rTMS</keyword>
  <keyword>Insular cortex</keyword>
  <keyword>PET</keyword>
  <keyword>[11C]-PHNO</keyword>
  <!-- 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/NCT02212405
org study id: 170/2010
nct id: NCT02212405
lead sponsor: 
collaborator: 
has dmc: Yes
Findings from this study may demonstrate how the insula contributes to reward pathways
      involved in addiction. There are three main hypotheses for this trial. The first is that
      inhibiting the insula using transcranial magnetic stimulation (TMS) will not cause noticeable
      changes of dopamine release in the striatum. The second is that stimulating the insula with
      TMS will increase dopamine release in the striatum, and will be visualized on PET imaging as
      decreased radiotracer binding. The third hypothesis is that the participants will not
      experience major side effects from TMS on the insula.
This project will take advantage of the recently developed Deep rTMS coil to target the
      insular cortex. Few studies have examined the possibility of using repetitive Transcranial
      Magnetic Stimulation (rTMS) for nicotine addiction and none so far have explored the use of a
      coil that specifically targets the insular region. The objective of this study is to test
      whether low and high-frequency rTMS of the insula modulates striatal dopamine (DA) release in
      healthy humans. Positron Emission Tomography (PET) with [11C]-(+)-PHNO, a radiotracer which
      is very sensitive to fluctuations in DA transmission in the human brain, will be used to
      assess the impact of rTMS on dopamine levels. This project will yield the first data in
      humans linking the insula to the DA system in vivo. These findings could lead to the
      identification of optimal parameters for Deep rTMS to use secondarily in a proof of principle
      clinical study in smokers.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in [11C]-(+)-PHNO binding
time frame: Participants will complete all sessions in a period of approximately 4 weeks.
description: [11C]-(+)-PHNO binding at D2/3 receptors will be measured with PET imaging following rTMS at 1Hz, 10Hz, and sham stimulation. Binding at regions of interest will be compared between trial conditions.
arm group label: rTMS Sham + PET
arm group type: Sham Comparator
description: An advanced sham coil will be used that mimicks the sound and sensation of real repetitive Transcranial Magnetic Stimulation. The repetitive Transcranial Magnetic Stimulation sham intervention is followed by radiotracer and PET.
arm group label: rTMS 1Hz + PET
arm group type: Experimental
description: Deep repetitive Transcranial Magnetic Stimulation will be applied to the insula for 30 minutes. This will consist of 20 trains each comprising of 50 pulses at 1Hz. The inter-train interval is 15 seconds. The intervention is followed by radiotracer and PET.
arm group label: rTMS 10Hz + PET.
arm group type: Experimental
description: Deep repetitive Transcranial Magnetic Stimulation will be applied to the insula for 30 minutes. This will consist of 34 trains each comprising of 30 pulses at 10Hz. The inter-train interval is 3 seconds. The intervention is followed by radiotracer and PET.
intervention type: Device
intervention name: repetitive Transcranial Magnetic Stimulation
description: Each participant will participate in all three arms to receive sham, 1hz and 10hz rTMS as well as PET imaging.
arm group label: rTMS 10Hz + PET.
arm group label: rTMS 1Hz + PET
other name: Deep Repetitive Transcranial Magnetic Stimulation
other name: DTMS HLRIADD-COIL, Model 102B
intervention type: Other
intervention name: repetitive Transcranial Magnetic Stimulation Sham
description: The sham coil is built in the same helmet of the active coil. The sham coil is has a circular shape and placed perpendicular to the scalp within the same helmet. This coil produces a similar sound and scalp sensation as the real coil.
arm group label: rTMS Sham + PET
criteria: 
gender: All
minimum age: 19 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bernard LeFoll, M.D., Ph.D
role: Principal Investigator
affiliation: CAMH
facility: 
country: Canada
url: http://www.camh.ca/en/research/Pages/research.aspx
description: Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Bernard Le Foll
investigator title: Principal investigator, MD, PhD, CCFP