<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/NCT03804619</url>
  </required_header>
  <id_info>
    <org_study_id>48431</org_study_id>
    <nct_id>NCT03804619</nct_id>
  </id_info>
  <brief_title>Accelerated Intermittent Theta-Burst Stimulation for Opiate Use Disorder</brief_title>
  <official_title>Accelerated Intermittent Theta-Burst Stimulation for Opiate Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</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>
      This study aims to examine whether multiple spaced sessions of intermittent theta-burst&#xD;
      transcranial magnetic stimulation (iTBS) induce anti-depressant responses and reduce opiate&#xD;
      cravings in adults with opiate use disorder (OUD). Additionally, we hope to identify whether&#xD;
      the effectiveness of iTBS is related to changes in functional connectivity between particular&#xD;
      brain areas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The proposed study aims to investigate the effectiveness of aiTBS applied to either the&#xD;
      L-DLPFC or the ACC for reducing SI in individuals with OUD and identify neural functional&#xD;
      connectivity changes underlying treatment response. 30 individuals with OUD who endorse&#xD;
      suicidal ideation will be recruited. The accelerated iTBS treatment will involve 10 daily&#xD;
      sessions of iTBS. Stimulation will be delivered to either the ACC or the L-DLPFC for 5&#xD;
      consecutive days. Suicidal ideation, depressive symptoms and opiate misuse will be measured&#xD;
      before and after the 5-day stimulation course. Functional magnetic resonance imaging (fMRI)&#xD;
      scans will also be carried out before and after stimulation to examine aiTBS-induced changes&#xD;
      in neural functional connectivity. Changes in suicidal ideation, depressive symptoms and&#xD;
      opiate misuse will be measured using both clinician-rated and self-report assessments.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">July 1, 2023</start_date>
  <completion_date type="Anticipated">December 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</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>Open label, two-site randomized trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Beck Scale for Suicidal Ideation (SSI) score</measure>
    <time_frame>After all stimulation sessions have been completed (approximately 48 hours after the final session)</time_frame>
    <description>19-item clinician administered assessment to measure the intensity, pervasiveness, and characteristics of suicidal ideation in adults. Scores range from 0-38.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Columbia Suicide Severity Scale (C-SSRS) score</measure>
    <time_frame>After all stimulation sessions have been completed (approximately 48 hours after the final session)</time_frame>
    <description>Self-report measure for suicidal ideation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Obsessive compulsive drug-use scale (OCDUS) score</measure>
    <time_frame>After all stimulation sessions have been completed (approximately 48 hours after the final session)</time_frame>
    <description>Self-report measure of drug craving. This questionnaire will be adapted to make it specific for opiate use.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Montgomery Asberg Depression Rating Scale (MADRS) score</measure>
    <time_frame>After all stimulation sessions have been completed (approximately 48 hours after the final session)</time_frame>
    <description>A 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Severity gradations for the MADRS have been proposed: 9-17 = mild depression, 18-34 = moderate depression, and ≥ 35 = severe depression. Scores range from 0-60.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Beck Depression Inventory II (BDI-II) score</measure>
    <time_frame>After all stimulation sessions have been completed (approximately 48 hours after the final session)</time_frame>
    <description>The Beck Depression Inventory (BDI-II) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in resting-state functional connectivity.</measure>
    <time_frame>After all stimulation sessions have been completed (approximately 48 hours after the final session)</time_frame>
    <description>Resting-state fMRI scans will be conducted before and after the course of aiTBS to examine changes in resting-state functional connectivity.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Opiate Dependence</condition>
  <condition>Suicidal Ideation</condition>
  <condition>Depression</condition>
  <condition>Opioid Use</condition>
  <condition>Opioid-Related Disorders</condition>
  <condition>Opioid-use Disorder</condition>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Left DLPFC aiTBS stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive aiTBS (intermittent theta burst stimulation) to a brain area called the left dorsolateral prefrontal cortex (L-DLPFC). Stimulation intensity will be individualized according to the individual's resting motor threshold.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ACC aiTBS stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive aiTBS (intermittent theta burst stimulation) to a brain area called the anterior cingulate cortex (ACC). Stimulation intensity will be individualized according to the individual's resting motor threshold.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Accelerated intermittent theta-burst stimulation (aiTBS)</intervention_name>
    <description>aiTBS is an effective form of non-invasive brain stimulation which has been FDA-approved for the treatment of Major Depressive Disorder (MDD)</description>
    <arm_group_label>ACC aiTBS stimulation</arm_group_label>
    <arm_group_label>Left DLPFC aiTBS stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Over 18 at the time of screening&#xD;
&#xD;
          2. Able to read, understand, and provide written, dated informed consent prior to&#xD;
             screening. Participants will be deemed likely to comply with study protocol and&#xD;
             communicate with study personnel about adverse events and other clinically important&#xD;
             information.&#xD;
&#xD;
          3. Diagnosed with Opiate Use Disorder, according to the criteria defined in the Diagnosis&#xD;
             and Statistical Manual of Mental Disorders.&#xD;
&#xD;
          4. Endorse suicidal ideation (score &gt;2 on the SSI-C).&#xD;
&#xD;
          5. Not in a current state of mania or psychosis (Young Mania Rating Scale)&#xD;
&#xD;
          6. In good general health, as ascertained by medical history.&#xD;
&#xD;
          7. If female, a status of non-childbearing potential or use of an acceptable form of&#xD;
             birth control per the following specific criteria:, a. Non-childbearing potential&#xD;
             (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized&#xD;
             (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her&#xD;
             last menses at least one year prior to screening); or, b. Childbearing potential, and&#xD;
             meets the following criteria. Childbearing potential, including women using any form&#xD;
             of hormonal birth control, on hormone replacement therapy started prior to 12 months&#xD;
             of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship&#xD;
             with a partner who has had a vasectomy, or is sexually abstinent. ii. Negative urinary&#xD;
             pregnancy test at screening, confirmed by a negative urinary pregnancy test at&#xD;
             randomization prior to receiving study treatment. iii. Willing and able to&#xD;
             continuously use one of the following methods of birth control during the course of&#xD;
             the study, defined as those which result in a low failure rate (i.e., less than 1% per&#xD;
             year) when used consistently and correctly: implants, injectable or patch hormonal&#xD;
             contraception, oral contraceptives, IUD, double-barrier contraception, sexual&#xD;
             abstinence. The form of birth control will be documented at screening and baseline.&#xD;
&#xD;
          8. Clear urine drugs test&#xD;
&#xD;
          9. Registered with a psychiatrist&#xD;
&#xD;
         10. On stable psychotropic medication or psychotherapy for at least 6 weeks prior to the&#xD;
             study with plans to continue throughout study enrollment.&#xD;
&#xD;
         11. Failed at least one anti-depressant trial (&gt;/=6 week duration at an effective dose)&#xD;
&#xD;
         12. Ability to tolerate clinical study procedures.&#xD;
&#xD;
         13. No contraindications for TMS or MRI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any abnormalities indicated on the MRI e.g. structural neurological condition, more&#xD;
             subcortical lesions than would be expected for age, stroke effecting stimulated area&#xD;
             or connected areas or any other clinically significant abnormality that might affect&#xD;
             safety, study participation, or confound interpretation of study results.&#xD;
&#xD;
          2. Metal implant in brain (e.g. deep brain stimulation), cardiac pacemaker, or cochlear&#xD;
&#xD;
          3. History of epilepsy/ seizures (including history of withdrawal/ provoked seizures)&#xD;
&#xD;
          4. Shrapnel or any ferromagnetic item in the head.&#xD;
&#xD;
          5. Pregnancy&#xD;
&#xD;
          6. Autism Spectrum disorder&#xD;
&#xD;
          7. Any current or past history of any physical condition which in the investigator's&#xD;
             opinion might put the subject at risk or interfere with study results interpretation.&#xD;
&#xD;
          8. Active substance use (&lt;1 week) or intoxication verified by toxicology screen--of&#xD;
             cocaine, amphetamines, benzodiazepines&#xD;
&#xD;
          9. Cognitive impairment (including dementia)&#xD;
&#xD;
         10. Current severe insomnia (must sleep a minimum of 5 hours the night before stimulation)&#xD;
&#xD;
         11. Current mania&#xD;
&#xD;
         12. Current unmanageable psychosis&#xD;
&#xD;
         13. Showing symptoms of withdrawal from alcohol or benzodiazepines&#xD;
&#xD;
         14. IQ&lt;70&#xD;
&#xD;
         15. Movement disorder&#xD;
&#xD;
         16. Any other indication the PI feels would comprise data.&#xD;
&#xD;
         17. Motor threshold value which does not enable treatment&#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>Gregory Sahlem, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Brendan Wong</last_name>
    <phone>650-374-0907</phone>
    <email>bwong14@stanford.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Brendan Wong</last_name>
      <email>bwong14@stanford.edu</email>
    </contact>
    <investigator>
      <last_name>Gregory Sahlem, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 11, 2019</study_first_submitted>
  <study_first_submitted_qc>January 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>April 12, 2023</last_update_submitted>
  <last_update_submitted_qc>April 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Gregory Sahlem</investigator_full_name>
    <investigator_title>Assistant Professor, Department of Psychiatry and Behavioral Sciences, Stanford University</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Suicidal Ideation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03804619
org study id: 48431
nct id: NCT03804619
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This study aims to examine whether multiple spaced sessions of intermittent theta-burst
      transcranial magnetic stimulation (iTBS) induce anti-depressant responses and reduce opiate
      cravings in adults with opiate use disorder (OUD). Additionally, we hope to identify whether
      the effectiveness of iTBS is related to changes in functional connectivity between particular
      brain areas.
The proposed study aims to investigate the effectiveness of aiTBS applied to either the
      L-DLPFC or the ACC for reducing SI in individuals with OUD and identify neural functional
      connectivity changes underlying treatment response. 30 individuals with OUD who endorse
      suicidal ideation will be recruited. The accelerated iTBS treatment will involve 10 daily
      sessions of iTBS. Stimulation will be delivered to either the ACC or the L-DLPFC for 5
      consecutive days. Suicidal ideation, depressive symptoms and opiate misuse will be measured
      before and after the 5-day stimulation course. Functional magnetic resonance imaging (fMRI)
      scans will also be carried out before and after stimulation to examine aiTBS-induced changes
      in neural functional connectivity. Changes in suicidal ideation, depressive symptoms and
      opiate misuse will be measured using both clinician-rated and self-report assessments.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open label, two-site randomized trial
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Beck Scale for Suicidal Ideation (SSI) score
time frame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
description: 19-item clinician administered assessment to measure the intensity, pervasiveness, and characteristics of suicidal ideation in adults. Scores range from 0-38.
measure: Change in Columbia Suicide Severity Scale (C-SSRS) score
time frame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
description: Self-report measure for suicidal ideation
measure: Change in Obsessive compulsive drug-use scale (OCDUS) score
time frame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
description: Self-report measure of drug craving. This questionnaire will be adapted to make it specific for opiate use.
measure: Change in Montgomery Asberg Depression Rating Scale (MADRS) score
time frame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
description: A 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Severity gradations for the MADRS have been proposed: 9-17 = mild depression, 18-34 = moderate depression, and ≥ 35 = severe depression. Scores range from 0-60.
measure: Change in Beck Depression Inventory II (BDI-II) score
time frame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
description: The Beck Depression Inventory (BDI-II) is a 21-item, self-report rating inventory that measures characteristic attitudes and symptoms of depression. BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.
measure: Change in resting-state functional connectivity.
time frame: After all stimulation sessions have been completed (approximately 48 hours after the final session)
description: Resting-state fMRI scans will be conducted before and after the course of aiTBS to examine changes in resting-state functional connectivity.
arm group label: Left DLPFC aiTBS stimulation
arm group type: Experimental
description: Participants will receive aiTBS (intermittent theta burst stimulation) to a brain area called the left dorsolateral prefrontal cortex (L-DLPFC). Stimulation intensity will be individualized according to the individual's resting motor threshold.
arm group label: ACC aiTBS stimulation
arm group type: Experimental
description: Participants will receive aiTBS (intermittent theta burst stimulation) to a brain area called the anterior cingulate cortex (ACC). Stimulation intensity will be individualized according to the individual's resting motor threshold.
intervention type: Device
intervention name: Accelerated intermittent theta-burst stimulation (aiTBS)
description: aiTBS is an effective form of non-invasive brain stimulation which has been FDA-approved for the treatment of Major Depressive Disorder (MDD)
arm group label: ACC aiTBS stimulation
arm group label: Left DLPFC aiTBS stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gregory Sahlem, MD
role: Principal Investigator
affiliation: Stanford University
last name: Brendan Wong
phone: 650-374-0907
email: bwong14@stanford.edu
facility: 
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Gregory Sahlem
investigator title: Assistant Professor, Department of Psychiatry and Behavioral Sciences, Stanford University
mesh term: Opioid-Related Disorders
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Suicidal Ideation
sharing ipd: No