<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/NCT03829761</url>
  </required_header>
  <id_info>
    <org_study_id>14918</org_study_id>
    <secondary_id>R21AA026573</secondary_id>
    <nct_id>NCT03829761</nct_id>
  </id_info>
  <brief_title>Cerebellar Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Alcohol Use Disorder</brief_title>
  <official_title>Cerebellar Repetitive Transcranial Magnetic Stimulation (rTMS) for Reduction of Negative Affect and Treatment of Alcohol Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Mind Research Network</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>The Mind Research Network</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of the current study is to investigate the effects of repetitive transcranial&#xD;
      magnetic stimulation (rTMS) on self-reported negative affect, cerebellar brain activation and&#xD;
      alcohol use outcomes in alcohol use disorder (AUD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To achieve study aims, 34 treatment seeking adults with AUD will be recruited from local&#xD;
      intensive outpatient (IOP) treatment programs and randomized to treatment with either&#xD;
      inhibitory 1Hz rTMS to cerebellar vermis given daily for 2 weeks (total of 10 sessions) or&#xD;
      sham. Alcohol use outcomes, self-reported negative affect, and craving will be obtained at&#xD;
      baseline, 1 day, 1 week and 6 weeks following rTMS termination. An fMRI scan during a Stroop&#xD;
      task will be obtained at baseline and 1 day after the final rTMS session.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 20, 2019</start_date>
  <completion_date type="Anticipated">April 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">April 30, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to drinking relapse as measured by the Time Line Follow Back</measure>
    <time_frame>8 weeks</time_frame>
    <description>Time to drinking relapse as measured by the Time Line Follow Back from baseline in days.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in percent days abstinent as measured by the Time Line Follow Back</measure>
    <time_frame>3 weeks</time_frame>
    <description>Change in percent days abstinent as measured by the Time Line Follow Back from the 90 days prior to day 1 to day 14-21 (post-treatment).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in self reported negative affect as measured by the Promise anger, anxiety and depression scales</measure>
    <time_frame>2 weeks</time_frame>
    <description>Change in self reported negative affect as measured by the Promise anger, anxiety and depression scale T scores from baseline to day 15 (post-treatment).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in cerebellar brain activation as indicated by percent signal change in the medial cerebellum during incongruent minus congruent trials during a multisensory Stroop task during fMRI</measure>
    <time_frame>2 weeks</time_frame>
    <description>Change in cerebellar brain activation as indicated by percent signal change in the medial cerebellum during incongruent minus congruent trials during a multisensory Stroop task during fMRI from baseline to day 15 (post-treatment). This will be calculated using a mask derived from preliminary data from a sample of 33 individuals with AUD at a single timepoint. Activation in this brain region was correlated with depression, anxiety, and recent drinking. Manuscript describing this result is under review (Wilcox et al.), and another manuscript describes the task in question (Wilcox et al. 2014 Cognitive Control Network Function in Alcohol Use Disorder Before and During Treatment With Lorazepam. Subst Use Misuse.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Cerebellar rTMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cerebellar rTMS. 1Hz repetitive transcranial magnetic stimulation (rTMS) to cerebellar vermis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham TMS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham TMS. Sham transcranial magnetic stimulation to cerebellar vermis.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Repetitive transcranial magnetic stimulation (rTMS)</intervention_name>
    <description>Repetitive transcranial magnetic stimulation (rTMS). Participants will undergo 10 daily sessions (Mon-Fri) of 30 minutes of 1Hz stimulation, for a total of 1800 pulses delivered.</description>
    <arm_group_label>Cerebellar rTMS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham transcranial magnetic stimulation</intervention_name>
    <description>Sham transcranial magnetic stimulation (TMS). Participants will undergo 10 daily sessions (Mon-Fri) of 30 minutes of sham stimulation. Sham stimulation will imitate the active rTMS but does not have active stimulation.</description>
    <arm_group_label>Sham TMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females age 18-65 meeting DSM-V criteria for moderate or severe AUD in the&#xD;
             past year;&#xD;
&#xD;
          -  Interested in cutting down or quitting drinking;&#xD;
&#xD;
          -  Able to provide voluntary informed consent;&#xD;
&#xD;
          -  Have at least 4 heavy drinking days (≥ 5 drinks per day for men, and ≥4 for women) in&#xD;
             the past 60 days;&#xD;
&#xD;
          -  Currently receiving treatment for alcohol use disorder.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe neurological conditions (TBI/stroke/history of a seizure/dementia and other&#xD;
             significant cognitive illnesses);&#xD;
&#xD;
          -  Other urgent medical problems, as determined by the study physician from the history&#xD;
             and physical exam;&#xD;
&#xD;
          -  Schizophrenia, schizoaffective disorder, bipolar I disorder&#xD;
&#xD;
          -  Suicidal thoughts (intent or plan) in the last month;&#xD;
&#xD;
          -  Current moderate or severe other SUD (except nicotine or marijuana) or other drug&#xD;
             (except nicotine or marijuana) use in the past month;&#xD;
&#xD;
          -  Active legal problems with the potential to result in incarceration;&#xD;
&#xD;
          -  Pregnancy or lactation, or child bearing age and sexually active but not on birth&#xD;
             control (barrier methods allowed);&#xD;
&#xD;
          -  Current daily use of anti-craving medications, antidepressants (at doses considered&#xD;
             therapeutic for depression), benzodiazepines, antipsychotics (at doses considered&#xD;
             therapeutic for psychosis or mood stabilization), mood stabilizers (at doses&#xD;
             considered therapeutic for mood stabilization);&#xD;
&#xD;
          -  Have previously undergone rTMS (to assure the blind is effective);&#xD;
&#xD;
          -  Personal or familial (in first degree relatives) history of epilepsy;&#xD;
&#xD;
          -  Any contraindication for Magnetic Resonance Imaging (MRI) or TMS including metal&#xD;
             shards or certain implants (pacemakers etc.) in the body.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jon M Houck, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Mind Research Network</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Mind Research Network</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 7, 2018</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Mind Research Network</investigator_affiliation>
    <investigator_full_name>Jon Houck</investigator_full_name>
    <investigator_title>Associate Professor of Translational Neuroscience</investigator_title>
  </responsible_party>
  <keyword>rTMS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Alcohol Drinking</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/NCT03829761
org study id: 14918
secondary id: R21AA026573
nct id: NCT03829761
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The objective of the current study is to investigate the effects of repetitive transcranial
      magnetic stimulation (rTMS) on self-reported negative affect, cerebellar brain activation and
      alcohol use outcomes in alcohol use disorder (AUD).
To achieve study aims, 34 treatment seeking adults with AUD will be recruited from local
      intensive outpatient (IOP) treatment programs and randomized to treatment with either
      inhibitory 1Hz rTMS to cerebellar vermis given daily for 2 weeks (total of 10 sessions) or
      sham. Alcohol use outcomes, self-reported negative affect, and craving will be obtained at
      baseline, 1 day, 1 week and 6 weeks following rTMS termination. An fMRI scan during a Stroop
      task will be obtained at baseline and 1 day after the final rTMS session.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Time to drinking relapse as measured by the Time Line Follow Back
time frame: 8 weeks
description: Time to drinking relapse as measured by the Time Line Follow Back from baseline in days.
measure: Change in percent days abstinent as measured by the Time Line Follow Back
time frame: 3 weeks
description: Change in percent days abstinent as measured by the Time Line Follow Back from the 90 days prior to day 1 to day 14-21 (post-treatment).
measure: Change in self reported negative affect as measured by the Promise anger, anxiety and depression scales
time frame: 2 weeks
description: Change in self reported negative affect as measured by the Promise anger, anxiety and depression scale T scores from baseline to day 15 (post-treatment).
measure: Change in cerebellar brain activation as indicated by percent signal change in the medial cerebellum during incongruent minus congruent trials during a multisensory Stroop task during fMRI
time frame: 2 weeks
description: Change in cerebellar brain activation as indicated by percent signal change in the medial cerebellum during incongruent minus congruent trials during a multisensory Stroop task during fMRI from baseline to day 15 (post-treatment). This will be calculated using a mask derived from preliminary data from a sample of 33 individuals with AUD at a single timepoint. Activation in this brain region was correlated with depression, anxiety, and recent drinking. Manuscript describing this result is under review (Wilcox et al.), and another manuscript describes the task in question (Wilcox et al. 2014 Cognitive Control Network Function in Alcohol Use Disorder Before and During Treatment With Lorazepam. Subst Use Misuse.
arm group label: Cerebellar rTMS
arm group type: Experimental
description: Cerebellar rTMS. 1Hz repetitive transcranial magnetic stimulation (rTMS) to cerebellar vermis.
arm group label: Sham TMS
arm group type: Sham Comparator
description: Sham TMS. Sham transcranial magnetic stimulation to cerebellar vermis.
intervention type: Device
intervention name: Repetitive transcranial magnetic stimulation (rTMS)
description: Repetitive transcranial magnetic stimulation (rTMS). Participants will undergo 10 daily sessions (Mon-Fri) of 30 minutes of 1Hz stimulation, for a total of 1800 pulses delivered.
arm group label: Cerebellar rTMS
intervention type: Device
intervention name: Sham transcranial magnetic stimulation
description: Sham transcranial magnetic stimulation (TMS). Participants will undergo 10 daily sessions (Mon-Fri) of 30 minutes of sham stimulation. Sham stimulation will imitate the active rTMS but does not have active stimulation.
arm group label: Sham TMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Jon M Houck, PhD
role: Principal Investigator
affiliation: The Mind Research Network
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Mind Research Network
investigator full name: Jon Houck
investigator title: Associate Professor of Translational Neuroscience
mesh term: Alcoholism
mesh term: Alcohol Drinking
sharing ipd: No