<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/NCT04495673</url>
  </required_header>
  <id_info>
    <org_study_id>PSYCH-2018-26724</org_study_id>
    <secondary_id>1UG3DA048508-01</secondary_id>
    <nct_id>NCT04495673</nct_id>
  </id_info>
  <brief_title>Combining Neuro-Imaging and Non-Invasive Brain Stimulation for Clinical Intervention in Opioid Use Disorder</brief_title>
  <official_title>Combining Neuro-Imaging and Non-Invasive Brain Stimulation for Clinical Intervention in Opioid Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overarching goal of this project is to expand the traditional expertise in non-invasive&#xD;
      neuromodulation at the University of Minnesota towards developing novel&#xD;
      paired-neuromodulation approaches using transcrancial direct current stimulation (tDCS) for&#xD;
      new addiction treatments that support long-term abstinence. This study will investigate&#xD;
      whether the pairing of dorsolateral prefrontal cortex (DLPFC) stimulation and cognitive&#xD;
      training can enhance functional connectivity between DLPFC and nucleus accumbens (NAcc). We&#xD;
      have identified higher functional connectivity between DLPFC and NAcc in alcoholics that have&#xD;
      successfully maintained abstinence for extended periods of time (7 years). This&#xD;
      paired-neuromodulation approach can potentially be used as a therapeutic intervention to&#xD;
      decrease substance use probability in addiction (e.g. opioid use disorder). The long term&#xD;
      goal is to develop new addiction treatments that support long-term abstinence in opioid use&#xD;
      disorder. The overall objective of this proposal is to enhance functional connectivity&#xD;
      between DLPFC and NAcc as a therapeutic intervention to enhance cognition and reduce&#xD;
      substance use rates in opioid use disorder.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 11, 2021</start_date>
  <completion_date type="Actual">February 22, 2022</completion_date>
  <primary_completion_date type="Actual">February 22, 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, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in circuit-based target engagement</measure>
    <time_frame>baseline; mid-test (week 2±1); post-test (week 3±1)</time_frame>
    <description>Participants will complete MRI sessions on a 3T scanner located in the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota. Participants will undergo resting-state MRI over an 8-minute scan in order to gather resting state functional connectivity. Significant within-subject increase (p&lt;.05, 1-tailed) in signal intensity (unitless measure) resting state functional connectivity (rsFC) of at least one frontally mediated network (frontal-striatal, frontal-insular, frontal-thalamic) in Active and Sham arms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in D-KEFS Trails T-Score</measure>
    <time_frame>baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)</time_frame>
    <description>The Trails subtest measures switching. The participant is presented with a sheet with several letters or numbers and is asked to follow the prompts (e.g. connect alternating numbers and letters). The time and number of errors for each of the 5 sheets is recorded and a T-score (range: 1-20) is calculated from this information. A higher T-score indicates higher capacity for switching, i.e., a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in D-KEFS Verbal Fluency T-Score</measure>
    <time_frame>baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)</time_frame>
    <description>The Verbal Fluency subtest measures executive control. Participants have to produce as many words as possible from a category in 60 seconds. The number of words produced and the number/position/type of errors are recorded. A T-score (range: 1-20) is calculated from this information. A higher T-score indicates higher executive control, i.e., a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in D-KEFS Color Word T-Score</measure>
    <time_frame>Time Frame: baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)</time_frame>
    <description>The Color-Word subtest measures switching capacity. The participant is presented with words demonstrating a mismatch between the name of a color (e.g., &quot;blue&quot;, &quot;green&quot;, or &quot;red&quot;) and the color it is printed on (i.e., the word &quot;red&quot; printed in blue ink instead of red ink). The participant must follow the prompts (e.g. &quot;Say the color of the ink this time&quot;) when responding. The number of correct answers and the time taken to complete the task are recorded, generating a T-score (range: 1-20). A higher T-score indicates higher capacity for switching i.e., a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in WAIS Digit Span T-Score</measure>
    <time_frame>baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)</time_frame>
    <description>The Digit Span subtest measures working memory. The participant is prompted to recall the order of digits they just heard (e.g., same order, backwards order, sequential order). There are two trials per item. Each item increases the difficulty by adding one digit. The total number correct generates a T-score (range: 1-20). A higher T-score indicates higher capacity for working memory, i.e., a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in WAIS Coding T-Score</measure>
    <time_frame>baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)</time_frame>
    <description>The Coding subtest measures switching capacity. The participant is presented with a symbol for each digit 1-9 (e.g., an upside-down &quot;T&quot; represents the number 2). The participant must translate the numbers into symbols, as fast as they can, for 120 seconds. The number of correctly-drawn symbols generates a T-score (range: 1-20). A higher T-score indicates higher capacity for switching, i.e., a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Timeline Follow Back (TLFB) Score</measure>
    <time_frame>baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)</time_frame>
    <description>The TLFB questionnaire measures substance use disorder severity. The questionnaire asks the participant about substance use in the past 30 days. The participant reports on a binary scale as to whether or not they have used a given substance. A greater number of days with drug use in the past month the participant used a substance equals a higher score. A higher score equals greater substance use disorder severity.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Opioid-Related Disorders</condition>
  <condition>Heroin Dependence</condition>
  <condition>Morphine Dependence</condition>
  <arm_group>
    <arm_group_label>tDCS with Cognitive Training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DLPFC stimulation with tDCS with simultaneous cognitive training</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham tDCS with Cognitive Training</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sham tDCS with simultaneous cognitive training</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Direct Current Stimulation (tDCS)</intervention_name>
    <description>Participants receive 10 sessions (2 5-visit blocks of 46 minutes) of active tDCS to DLPFC (dorsolateral prefrontal cortex)</description>
    <arm_group_label>tDCS with Cognitive Training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Transcranial Direct Current Stimulation (tDCS)</intervention_name>
    <description>Participants receive 10 sessions (1 5-visit block of 46 minutes of active tDCS and 1 5-visit block of sham tDCS)</description>
    <arm_group_label>Sham tDCS with Cognitive Training</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive Training</intervention_name>
    <description>Executive functioning tasks</description>
    <arm_group_label>Sham tDCS with Cognitive Training</arm_group_label>
    <arm_group_label>tDCS with Cognitive Training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Current diagnosis of opioid use disorder&#xD;
&#xD;
          -  Enrolled in a methadone treatment program for at least 2 months in Hennepin Healthcare&#xD;
             and be clinically stable.&#xD;
&#xD;
          -  Meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic&#xD;
             criteria for opioid use disorder&#xD;
&#xD;
          -  Participants may have current comorbid drug use, but their primary substance use&#xD;
             disorder diagnosis must to be based on opioid use.&#xD;
&#xD;
          -  Participants must have the intention to remain in the methadone treatment program&#xD;
             until the end of the intervention portion of the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any medical condition or treatment with neurological sequelae (i.e. stroke, tumor,&#xD;
             loss of consciousness&gt;30 min, HIV)&#xD;
&#xD;
          -  Head injury resulting in a skull fracture or a loss of consciousness exceeding 30&#xD;
             minutes (i.e., moderate or severe TBI)&#xD;
&#xD;
          -  Any contraindications for tDCS or MRI scanning (tDCS contraindication: actively&#xD;
             receiving treatment for seizures or epilepsy; MRI contraindications; metal implants,&#xD;
             pacemakers or any other implanted electrical device, injury with metal, braces, dental&#xD;
             implants, non-removable body piercings, pregnancy, breathing or moving disorder)&#xD;
&#xD;
          -  Current active psychosis or mania&#xD;
&#xD;
          -  Presence of a condition that would render study measures difficult or impossible to&#xD;
             administer or interpret (e.g. current mania, active psychosis)&#xD;
&#xD;
          -  Primary current substance use disorder diagnosis on a substance other than opioid&#xD;
             except for caffeine or nicotine&#xD;
&#xD;
          -  Current stimulant use disorder (need to be free of stimulant use for at least 1 month)&#xD;
&#xD;
          -  History of electroconvulsive therapy or cortical energy exposure within the past 12&#xD;
             months, including participation in any other neuromodulation studies&#xD;
&#xD;
          -  incarceration&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kelvin Lim, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jazmin Camchong, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>December 27, 2022</last_update_submitted>
  <last_update_submitted_qc>December 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 28, 2022</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>Opioid-Related Disorders</mesh_term>
    <mesh_term>Heroin Dependence</mesh_term>
    <mesh_term>Morphine Dependence</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>May 30, 2023</submitted>
    <returned>June 23, 2023</returned>
  </pending_results>
  <!-- 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/NCT04495673
org study id: PSYCH-2018-26724
secondary id: 1UG3DA048508-01
nct id: NCT04495673
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
The overarching goal of this project is to expand the traditional expertise in non-invasive
      neuromodulation at the University of Minnesota towards developing novel
      paired-neuromodulation approaches using transcrancial direct current stimulation (tDCS) for
      new addiction treatments that support long-term abstinence. This study will investigate
      whether the pairing of dorsolateral prefrontal cortex (DLPFC) stimulation and cognitive
      training can enhance functional connectivity between DLPFC and nucleus accumbens (NAcc). We
      have identified higher functional connectivity between DLPFC and NAcc in alcoholics that have
      successfully maintained abstinence for extended periods of time (7 years). This
      paired-neuromodulation approach can potentially be used as a therapeutic intervention to
      decrease substance use probability in addiction (e.g. opioid use disorder). The long term
      goal is to develop new addiction treatments that support long-term abstinence in opioid use
      disorder. The overall objective of this proposal is to enhance functional connectivity
      between DLPFC and NAcc as a therapeutic intervention to enhance cognition and reduce
      substance use rates in opioid use disorder.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Changes in circuit-based target engagement
time frame: baseline; mid-test (week 2±1); post-test (week 3±1)
description: Participants will complete MRI sessions on a 3T scanner located in the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota. Participants will undergo resting-state MRI over an 8-minute scan in order to gather resting state functional connectivity. Significant within-subject increase (p<.05, 1-tailed) in signal intensity (unitless measure) resting state functional connectivity (rsFC) of at least one frontally mediated network (frontal-striatal, frontal-insular, frontal-thalamic) in Active and Sham arms.
measure: Change in D-KEFS Trails T-Score
time frame: baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)
description: The Trails subtest measures switching. The participant is presented with a sheet with several letters or numbers and is asked to follow the prompts (e.g. connect alternating numbers and letters). The time and number of errors for each of the 5 sheets is recorded and a T-score (range: 1-20) is calculated from this information. A higher T-score indicates higher capacity for switching, i.e., a better outcome.
measure: Change in D-KEFS Verbal Fluency T-Score
time frame: baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)
description: The Verbal Fluency subtest measures executive control. Participants have to produce as many words as possible from a category in 60 seconds. The number of words produced and the number/position/type of errors are recorded. A T-score (range: 1-20) is calculated from this information. A higher T-score indicates higher executive control, i.e., a better outcome.
measure: Change in D-KEFS Color Word T-Score
time frame: Time Frame: baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)
description: The Color-Word subtest measures switching capacity. The participant is presented with words demonstrating a mismatch between the name of a color (e.g., "blue", "green", or "red") and the color it is printed on (i.e., the word "red" printed in blue ink instead of red ink). The participant must follow the prompts (e.g. "Say the color of the ink this time") when responding. The number of correct answers and the time taken to complete the task are recorded, generating a T-score (range: 1-20). A higher T-score indicates higher capacity for switching i.e., a better outcome.
measure: Change in WAIS Digit Span T-Score
time frame: baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)
description: The Digit Span subtest measures working memory. The participant is prompted to recall the order of digits they just heard (e.g., same order, backwards order, sequential order). There are two trials per item. Each item increases the difficulty by adding one digit. The total number correct generates a T-score (range: 1-20). A higher T-score indicates higher capacity for working memory, i.e., a better outcome.
measure: Change in WAIS Coding T-Score
time frame: baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)
description: The Coding subtest measures switching capacity. The participant is presented with a symbol for each digit 1-9 (e.g., an upside-down "T" represents the number 2). The participant must translate the numbers into symbols, as fast as they can, for 120 seconds. The number of correctly-drawn symbols generates a T-score (range: 1-20). A higher T-score indicates higher capacity for switching, i.e., a better outcome.
measure: Change in Timeline Follow Back (TLFB) Score
time frame: baseline; mid-test (week 2±1); post-test (week 3±1); Follow-up 1 (post-test + 1 month), Follow-up 2 (post-test + 2 months)
description: The TLFB questionnaire measures substance use disorder severity. The questionnaire asks the participant about substance use in the past 30 days. The participant reports on a binary scale as to whether or not they have used a given substance. A greater number of days with drug use in the past month the participant used a substance equals a higher score. A higher score equals greater substance use disorder severity.
arm group label: tDCS with Cognitive Training
arm group type: Experimental
description: DLPFC stimulation with tDCS with simultaneous cognitive training
arm group label: Sham tDCS with Cognitive Training
arm group type: Active Comparator
description: Sham tDCS with simultaneous cognitive training
intervention type: Device
intervention name: Transcranial Direct Current Stimulation (tDCS)
description: Participants receive 10 sessions (2 5-visit blocks of 46 minutes) of active tDCS to DLPFC (dorsolateral prefrontal cortex)
arm group label: tDCS with Cognitive Training
intervention type: Device
intervention name: Sham Transcranial Direct Current Stimulation (tDCS)
description: Participants receive 10 sessions (1 5-visit block of 46 minutes of active tDCS and 1 5-visit block of sham tDCS)
arm group label: Sham tDCS with Cognitive Training
intervention type: Behavioral
intervention name: Cognitive Training
description: Executive functioning tasks
arm group label: Sham tDCS with Cognitive Training
arm group label: tDCS with Cognitive Training
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Kelvin Lim, MD
role: Principal Investigator
affiliation: University of Minnesota
last name: Jazmin Camchong, PhD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
mesh term: Heroin Dependence
mesh term: Morphine Dependence
submitted: May 30, 2023
returned: June 23, 2023