<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/NCT03238859</url>
  </required_header>
  <id_info>
    <org_study_id>00046438</org_study_id>
    <secondary_id>R21DA041610</secondary_id>
    <nct_id>NCT03238859</nct_id>
  </id_info>
  <brief_title>10 Days of Theta Burst Stimulation as a Tool to Treat Cocaine Dependence</brief_title>
  <official_title>10 Days of Medial Prefrontal Cortex Theta Burst Stimulation (MPFC cTBS) as a Tool to Improve Clinical Outcomes and Decrease Frontal-striatal Reactivity to Cues Among Treatment-engaged Cocaine and Alcohol Users</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</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>Medical University of South Carolina</source>
  <oversight_info>
    <has_dmc>Yes</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 goal of this double-blind sham controlled study is to evaluate the effeicacy of&#xD;
      continuous theta burst stimulation to the frontal pole as a tool to decrease drug cue&#xD;
      reactivity and improve treatment outcomes in treatment-engaged cocaine and alcohol users. All&#xD;
      participants will be randomized to receive 10 days of real or sham rTMS to the frontal pole.&#xD;
      Brain imaging data and behavioral assessments will be collected at 4 time points - before&#xD;
      TMS, after 10 days of TMS, 1 month follow up and 2 month follow up.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cocaine dependence is a particularly difficult substance use disorder to treat. There is&#xD;
      currently a lot of scientific inertia focused on the development of novel, neural circuit&#xD;
      based strategies for intervention. A prior NARC funded pilot project in non-treatment seeking&#xD;
      cocaine users demonstrated that a single session of medial prefrontal cortex theta burst&#xD;
      stimulation (MPFC cTBS) decreases baseline frontal-striatal activity in limbic regions and&#xD;
      decreases neural responses to cocaine uses. The effects of a single session however, erode&#xD;
      over the first few hours after treatment. Sustainable effects require multiple days of&#xD;
      treatment. GOAL: The next steps in pursuing this as a novel treatment are to 1) apply it to&#xD;
      treatment-engaged patients and 2) determine whether several sessions of cTBS will produce&#xD;
      sustainable and clinically-meaningful changes in cocaine use among these patients.&#xD;
&#xD;
      DESIGN: Treatment-engaged cocaine users and heavy alcohol users will be randomized to receive&#xD;
      10 sessions of real or sham LTD-like MPFC cTBS. This will be achieved by leveraging our&#xD;
      existing partnership with the MUSC Center for Drug and Alcohol Programs (CDAP) and the&#xD;
      Veterans Administration Substance Abuse Treatment Center Program (SATC) - which both provide&#xD;
      a 4 week intensive outpatient treatment program. MPFC cTBS will be given during weeks 2 and 3&#xD;
      of the program. Functional MRI data and clinical assessments will be acquired during weeks 1,&#xD;
      4, and at participant's 1 month and 2 month Accountability/Continuity visits. Hypothesis:&#xD;
      real cTBS treatment will enhance clinical outcomes (Aim 1 - including retention rates, number&#xD;
      of clean urine drug screens during CDAP treatment, relapse rates at 1 and 2 months) and will&#xD;
      produce a sustainable decrease in neural reactivity to cocaine cues (Aim 2 - week 1 versus&#xD;
      week 4, 1 month &amp; 2 month follow ups).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2016</start_date>
  <completion_date type="Actual">June 7, 2019</completion_date>
  <primary_completion_date type="Actual">June 7, 2019</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Drug cue reactivity</measure>
    <time_frame>Baseline visit and 1 month follow up</time_frame>
    <description>The effect of real versus sham cTBS on drug cue reactivity will be assessed by comparing the brain activity in the limbic system</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Clean Urine Drug Screens</measure>
    <time_frame>1 month and 2 month follow up</time_frame>
    <description>The effect of real versus sham cTBS on the number of clean urine drug screens will be assessed at the 1 and 2 month follow up.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">84</enrollment>
  <condition>Cocaine Dependence</condition>
  <condition>Alcohol Dependence</condition>
  <arm_group>
    <arm_group_label>Real cTBS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 days of real cTBS treatment will be given (3600 pulses to the left frontal pole as defined by EEG coordinate: FP1; 60 second pause after 1800 pulses; 110% RMT including a 30 second initial ramp period 80%-110% RMT; Magventure MagPro X100 Cool Coil).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham cTBS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>10 days of sham cTBS treatment will be given (3600 pulses to the left frontal pole as defined by EEG coordinate: FP1; 60 second pause after 1800 pulses; 110% RMT including a 30 second initial ramp period 80%-110% RMT; Magventure MagPro X100 Cool Coil).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Real cTBS</intervention_name>
    <description>This will be delivered with the Magventure Magpro system; 3600 pulses with the active sham coil (double blinded using the USB key)</description>
    <arm_group_label>Real cTBS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham cTBS</intervention_name>
    <description>This will be delivered with the sham Magventure Magpro system; 3600 pulses with the active sham coil (double blinded using the USB key)</description>
    <arm_group_label>Sham cTBS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals from 21-65 years old currently enrolled in an intensive outpatient&#xD;
             treatment program.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants will be excluded if they are not between 21-65 years old, have current or&#xD;
             prior dependence (DSM-IV, because a DSM-V version of the SCID is not yet available) on&#xD;
             prescription or psychoactive drugs other than cocaine, alcohol, or nicotine but&#xD;
             including marijuana; past 6 month abuse of any prescription or psychoactive drugs&#xD;
             excluding cocaine, marijuana, alcohol or nicotine, lifetime history of head injury&#xD;
             with loss of consciousness, being pregnant or breast feeding, unstable medical illness&#xD;
             (e.g., hypertension, diabetes, myocardial infarction), presence of ferromagnetic metal&#xD;
             in their body, history of seizures. Additionally, to mitigate any potential risk of&#xD;
             seizures. As mentioned above, all participants will receive the Clinical Institute&#xD;
             Withdrawal Assessment of Alcohol (CIWAar) assessment before each TMS visit.&#xD;
             Individuals with a CIWA score &gt;5 will be excused from the study. All individuals with&#xD;
             a history of medical detoxification or hospitalization for AUD (per the Assessments&#xD;
             listed above), self-reported alcohol withdrawal seizures, or delirium tremens will be&#xD;
             excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Colleen A Hanlon, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ralph H Johnson Veterans Medical Center</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>September 1, 2016</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>March 10, 2020</last_update_submitted>
  <last_update_submitted_qc>March 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of South Carolina</investigator_affiliation>
    <investigator_full_name>Colleen A Hanlon, PhD</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Cocaine-Related Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>No individual participant data will be shared. All data is deidentified.</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/NCT03238859
org study id: 00046438
secondary id: R21DA041610
nct id: NCT03238859
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The goal of this double-blind sham controlled study is to evaluate the effeicacy of
      continuous theta burst stimulation to the frontal pole as a tool to decrease drug cue
      reactivity and improve treatment outcomes in treatment-engaged cocaine and alcohol users. All
      participants will be randomized to receive 10 days of real or sham rTMS to the frontal pole.
      Brain imaging data and behavioral assessments will be collected at 4 time points - before
      TMS, after 10 days of TMS, 1 month follow up and 2 month follow up.
Cocaine dependence is a particularly difficult substance use disorder to treat. There is
      currently a lot of scientific inertia focused on the development of novel, neural circuit
      based strategies for intervention. A prior NARC funded pilot project in non-treatment seeking
      cocaine users demonstrated that a single session of medial prefrontal cortex theta burst
      stimulation (MPFC cTBS) decreases baseline frontal-striatal activity in limbic regions and
      decreases neural responses to cocaine uses. The effects of a single session however, erode
      over the first few hours after treatment. Sustainable effects require multiple days of
      treatment. GOAL: The next steps in pursuing this as a novel treatment are to 1) apply it to
      treatment-engaged patients and 2) determine whether several sessions of cTBS will produce
      sustainable and clinically-meaningful changes in cocaine use among these patients.

      DESIGN: Treatment-engaged cocaine users and heavy alcohol users will be randomized to receive
      10 sessions of real or sham LTD-like MPFC cTBS. This will be achieved by leveraging our
      existing partnership with the MUSC Center for Drug and Alcohol Programs (CDAP) and the
      Veterans Administration Substance Abuse Treatment Center Program (SATC) - which both provide
      a 4 week intensive outpatient treatment program. MPFC cTBS will be given during weeks 2 and 3
      of the program. Functional MRI data and clinical assessments will be acquired during weeks 1,
      4, and at participant's 1 month and 2 month Accountability/Continuity visits. Hypothesis:
      real cTBS treatment will enhance clinical outcomes (Aim 1 - including retention rates, number
      of clean urine drug screens during CDAP treatment, relapse rates at 1 and 2 months) and will
      produce a sustainable decrease in neural reactivity to cocaine cues (Aim 2 - week 1 versus
      week 4, 1 month & 2 month follow ups).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Drug cue reactivity
time frame: Baseline visit and 1 month follow up
description: The effect of real versus sham cTBS on drug cue reactivity will be assessed by comparing the brain activity in the limbic system
measure: Number of Clean Urine Drug Screens
time frame: 1 month and 2 month follow up
description: The effect of real versus sham cTBS on the number of clean urine drug screens will be assessed at the 1 and 2 month follow up.
arm group label: Real cTBS
arm group type: Experimental
description: 10 days of real cTBS treatment will be given (3600 pulses to the left frontal pole as defined by EEG coordinate: FP1; 60 second pause after 1800 pulses; 110% RMT including a 30 second initial ramp period 80%-110% RMT; Magventure MagPro X100 Cool Coil).
arm group label: Sham cTBS
arm group type: Sham Comparator
description: 10 days of sham cTBS treatment will be given (3600 pulses to the left frontal pole as defined by EEG coordinate: FP1; 60 second pause after 1800 pulses; 110% RMT including a 30 second initial ramp period 80%-110% RMT; Magventure MagPro X100 Cool Coil).
intervention type: Device
intervention name: Real cTBS
description: This will be delivered with the Magventure Magpro system; 3600 pulses with the active sham coil (double blinded using the USB key)
arm group label: Real cTBS
intervention type: Device
intervention name: Sham cTBS
description: This will be delivered with the sham Magventure Magpro system; 3600 pulses with the active sham coil (double blinded using the USB key)
arm group label: Sham cTBS
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: No
last name: Colleen A Hanlon, PhD
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Medical University of South Carolina
investigator full name: Colleen A Hanlon, PhD
investigator title: Associate Professor
mesh term: Alcoholism
mesh term: Cocaine-Related Disorders
sharing ipd: No
ipd description: No individual participant data will be shared. All data is deidentified.