<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/NCT04432493</url>
  </required_header>
  <id_info>
    <org_study_id>Pro2018002739</org_study_id>
    <nct_id>NCT04432493</nct_id>
  </id_info>
  <brief_title>Using Combined EEG and Non-invasive Brain Stimulation to Examine and Improve Reward Functioning in Opioid Use Disorder</brief_title>
  <official_title>Using Combined EEG and Non-invasive Brain Stimulation to Examine and Improve Reward Functioning in Opioid Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rutgers University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rutgers, The State University of New Jersey</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aims of this study are to identify impaired cognitive control in opioid use&#xD;
      disorder (OUD) and subsequently to examine the effects of transcranial magnetic stimulation&#xD;
      (TMS) on reward processing, as measured by the reward positivity (an electrophysiological&#xD;
      signal) in people with OUD. To this end, the investigators will adopt a randomized&#xD;
      sham-controlled trial to evaluate the efficacy of Ri-TMS on cognitive control in OUD.&#xD;
&#xD;
      The investigators hypothesize that Ri-TMS will be successful in modulating the reward&#xD;
      positivity in opioid users in the active TMS condition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The design is primarily a randomized control-trial design, comparing the effects of placebo&#xD;
      (sham) and active TMS stimulation on reward processing across two groups of participants -&#xD;
      healthy controls and opioid users.&#xD;
&#xD;
      Participants will be asked to engage in a virtual T-maze task, a reward-based choice task&#xD;
      that elicits robust reward positivities. During this task participants will receive&#xD;
      simultaneous EEG/TMS, while they engage in the virtual T-maze decision making task, used in&#xD;
      our previous reward positivity studies on SUDs. ERPs will be recorded throughout the T-Maze&#xD;
      task, and the reward positivity will be measured as the difference in maximum amplitude&#xD;
      between reward and no-reward feedback conditions.&#xD;
&#xD;
      The TMS coil will be positioned using a an Adept Viper s850 robotic arm (SmartMove, ANT&#xD;
      Neuro, Enschede, The Netherlands), providing precise targeting of the predetermined left&#xD;
      dorsolateral prefrontal (DLPFC) coordinate (&lt; 10 mm from the scalp, orientated at a 45º&#xD;
      angle). Participants in the active TMS condition will receive rTMS pulses throughout the&#xD;
      duration of the T-Maze task, with a maximum of 2000 pulses delivered to each participant.&#xD;
      Identical parameters will be applied to the SHAM group with the exception that the TMS coil&#xD;
      will be flipped 180º to mimic auditory stimulation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 20, 2020</start_date>
  <completion_date type="Actual">August 31, 2022</completion_date>
  <primary_completion_date type="Actual">August 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Participants will be blinded as to TMS condition (active or sham)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Reward Positivity</measure>
    <time_frame>Day 0 (day of testing)</time_frame>
    <description>The reward positivity is an event-related brain potential, sensitive to reward feedback. The reward positivity will be measured during the t-maze task, where participants will receive feedback on choices (Reward, No-reward). Reward positivity amplitude will be determined by identifying the maximum absolute amplitude of the difference wave within a 200- to 400-ms window following feedback onset. The reward positivity will be evaluated along front-central electrodes (Fz, FCz, Cz).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">92</enrollment>
  <condition>Opioid-use Disorder</condition>
  <arm_group>
    <arm_group_label>Active TMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the active condition will receive repetitive TMS (rTMS), delivered at 110% of participants' resting motor threshold at 10 Hz continuously over the predefined DLFPC target for a total of 2000 pulses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham TMS</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Identical parameters will be applied to the SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active repetitive transcranial magnetic stimulation (rTMS)</intervention_name>
    <description>rTMS will be used to stimulate neuronal activity of the dorsolateral prefrontal cortex (DLPFC). Participants will receive no more than 2000 pulses of rTMS at 110% of participants' resting motor threshold at 10 Hz continuously for the duration of the t-maze task.</description>
    <arm_group_label>Active TMS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham repetitive transcranial magnetic stimulation (rTMS)</intervention_name>
    <description>Sham TMS will be used to mimic the auditory sensation of the Active rTMS condition. Protocols for the sham condition will be the same as the active condition, however the TMS coil will be flipped 180 degrees so that participants in this condition will not receive any active stimulation.</description>
    <arm_group_label>Sham TMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Native English speakers&#xD;
&#xD;
          -  Males and Females aged 18-55 years old&#xD;
&#xD;
          -  Ability to provide informed written or verbal consent&#xD;
&#xD;
          -  Opioid dependent individuals (according to the Alcohol, Smoking and Substance&#xD;
             Involvement Screening Test opioid dependence score), or&#xD;
&#xD;
          -  Healthy controls with no history of significant substance use&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Un-correctable visual impairment&#xD;
&#xD;
          -  Uninterruptable central nervous system medication&#xD;
&#xD;
          -  TMS contraindications (e.g., pregnancy, braces, history of seizures, metal implants).&#xD;
&#xD;
          -  History of neurological or psychiatric illness&#xD;
&#xD;
          -  Diagnosed learning disability&#xD;
&#xD;
          -  History of significant head injury (loss of consciousness for more than five minutes)&#xD;
&#xD;
          -  Substance abuse (Participants who score above 39.5 on the Global Continuum of&#xD;
             Substance Risk scale of the Alcohol, Smoking and Substance Involvement Screening Test&#xD;
             - controls only)&#xD;
&#xD;
          -  Use of psychoactive or vasoactive medications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kathryn Biernacki, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rutgers University - Newark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rutgers University - Newark</name>
      <address>
        <city>Newark</city>
        <state>New Jersey</state>
        <zip>07102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 11, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rutgers University</investigator_affiliation>
    <investigator_full_name>Travis Baker, PhD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Transcranial magnetic stimulation</keyword>
  <keyword>Reward processing</keyword>
  <keyword>Cognitive control</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
    <mesh_term>Substance-Related Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data may be uploaded to an open source framework. All data will be de-identified.</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/NCT04432493
org study id: Pro2018002739
nct id: NCT04432493
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The primary aims of this study are to identify impaired cognitive control in opioid use
      disorder (OUD) and subsequently to examine the effects of transcranial magnetic stimulation
      (TMS) on reward processing, as measured by the reward positivity (an electrophysiological
      signal) in people with OUD. To this end, the investigators will adopt a randomized
      sham-controlled trial to evaluate the efficacy of Ri-TMS on cognitive control in OUD.

      The investigators hypothesize that Ri-TMS will be successful in modulating the reward
      positivity in opioid users in the active TMS condition.
The design is primarily a randomized control-trial design, comparing the effects of placebo
      (sham) and active TMS stimulation on reward processing across two groups of participants -
      healthy controls and opioid users.

      Participants will be asked to engage in a virtual T-maze task, a reward-based choice task
      that elicits robust reward positivities. During this task participants will receive
      simultaneous EEG/TMS, while they engage in the virtual T-maze decision making task, used in
      our previous reward positivity studies on SUDs. ERPs will be recorded throughout the T-Maze
      task, and the reward positivity will be measured as the difference in maximum amplitude
      between reward and no-reward feedback conditions.

      The TMS coil will be positioned using a an Adept Viper s850 robotic arm (SmartMove, ANT
      Neuro, Enschede, The Netherlands), providing precise targeting of the predetermined left
      dorsolateral prefrontal (DLPFC) coordinate (< 10 mm from the scalp, orientated at a 45º
      angle). Participants in the active TMS condition will receive rTMS pulses throughout the
      duration of the T-Maze task, with a maximum of 2000 pulses delivered to each participant.
      Identical parameters will be applied to the SHAM group with the exception that the TMS coil
      will be flipped 180º to mimic auditory stimulation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
masking description: Participants will be blinded as to TMS condition (active or sham)
measure: Reward Positivity
time frame: Day 0 (day of testing)
description: The reward positivity is an event-related brain potential, sensitive to reward feedback. The reward positivity will be measured during the t-maze task, where participants will receive feedback on choices (Reward, No-reward). Reward positivity amplitude will be determined by identifying the maximum absolute amplitude of the difference wave within a 200- to 400-ms window following feedback onset. The reward positivity will be evaluated along front-central electrodes (Fz, FCz, Cz).
arm group label: Active TMS
arm group type: Experimental
description: Participants in the active condition will receive repetitive TMS (rTMS), delivered at 110% of participants' resting motor threshold at 10 Hz continuously over the predefined DLFPC target for a total of 2000 pulses
arm group label: Sham TMS
arm group type: Placebo Comparator
description: Identical parameters will be applied to the SHAM group with the exception that the TMS coil will be flipped 180º to mimic auditory stimulation
intervention type: Device
intervention name: Active repetitive transcranial magnetic stimulation (rTMS)
description: rTMS will be used to stimulate neuronal activity of the dorsolateral prefrontal cortex (DLPFC). Participants will receive no more than 2000 pulses of rTMS at 110% of participants' resting motor threshold at 10 Hz continuously for the duration of the t-maze task.
arm group label: Active TMS
intervention type: Device
intervention name: Sham repetitive transcranial magnetic stimulation (rTMS)
description: Sham TMS will be used to mimic the auditory sensation of the Active rTMS condition. Protocols for the sham condition will be the same as the active condition, however the TMS coil will be flipped 180 degrees so that participants in this condition will not receive any active stimulation.
arm group label: Sham TMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kathryn Biernacki, PhD
role: Principal Investigator
affiliation: Rutgers University - Newark
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Rutgers University
investigator full name: Travis Baker, PhD
investigator title: Principal Investigator
mesh term: Opioid-Related Disorders
mesh term: Substance-Related Disorders
sharing ipd: No
ipd description: Data may be uploaded to an open source framework. All data will be de-identified.