<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/NCT03809286</url>
  </required_header>
  <id_info>
    <org_study_id>7691</org_study_id>
    <secondary_id>1K23AA028295</secondary_id>
    <secondary_id>5R21AA026049</secondary_id>
    <nct_id>NCT03809286</nct_id>
  </id_info>
  <brief_title>The Effect of rTMS to the Prefrontal Cortex in Alcohol Use Disorder</brief_title>
  <acronym>MAGNA</acronym>
  <official_title>The Effect of rTMS to the Prefrontal Cortex in Alcohol Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</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>New York State Psychiatric Institute</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_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to investigate a treatment approach for alcohol use disorder (AUD)&#xD;
      using a novel form of brain stimulation called deep repetitive transcranial magnetic&#xD;
      stimulation (rTMS). The investigators will be targeting frontal regions of the brain that are&#xD;
      important for memory and decision making. These brain regions have been shown to be impaired&#xD;
      in patients with AUD. Previous studies have mostly used rTMS to a different frontal brain&#xD;
      region that is not as deep. These studies have shown that rTMS can reduce craving for&#xD;
      alcohol, but there is a lack of research showing that rTMS impacts alcohol consumption.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study aims to examine the effect of rTMS on alcohol drinking behavior in an observed&#xD;
      laboratory setting. Participants with AUD will be recruited and admitted to the inpatient&#xD;
      unit for the whole study. After a brief detoxification period, they will receive 3 weeks of&#xD;
      rTMS while in the research unit. Before and after the 3 weeks of stimulation, participants&#xD;
      will participate in a decision-making experiment where they can choose to have an alcoholic&#xD;
      drink or the equivalent amount of money that the drink would cost (alcohol&#xD;
      self-administration sessions). The investigators will examine their response to alcohol, as&#xD;
      well as their performance on tasks that relate to impulsivity and memory. Participants will&#xD;
      also undergo an MRI scan (with spectroscopy) before and after the stimulation period to look&#xD;
      at changes in the medial prefrontal cortex of the brain. Participants will then meet with a&#xD;
      study physician for 6 weeks after the study for assessments of alcohol use and medical&#xD;
      management sessions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 24, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 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>
    <intervention_model_description>active vs. sham stimulation</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the choice to self-administer alcohol in the laboratory as assessed by counting the number of drinks consumed in the 2-hour laboratory session.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Participants will participate in alcohol self-administration sessions in which they are presented with the choice of alcohol or money. The investigators will study the change in choices to choose alcohol during these sessions. There will be one session prior to rTMS and one after 3 weeks of rTMS.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0.</measure>
    <time_frame>10 weeks</time_frame>
    <description>Adverse events will be assessed in recorded in accordance with CTCAE v4.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in craving for alcohol measured using the Alcohol Urge Questionnaire (AUQ).</measure>
    <time_frame>4 weeks</time_frame>
    <description>This AUQ (Bohn et al. 1995) is an 8-item self report questionnaire where participants rate a seven-point Likert scale with responses ranging from &quot;strongly disagree&quot; to &quot;strongly agree&quot;, and a total score is derived from the sum of these items following reverse scoring of two items. A lower score is a better outcome which represents less desire to drink. Scores range from 8-56.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in GABA in the mPFC and ACC as measured with magnetic resonance spectroscopy (MRS).</measure>
    <time_frame>4 weeks</time_frame>
    <description>MRS is performed by using an MRI machine to study metabolites and neurotransmitters in the brain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in abstinence from alcohol following discharge assessed with the Time Line Follow Back Interview.</measure>
    <time_frame>10 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cognitive control as measured by using the Frontal Assessment Battery (FAB).</measure>
    <time_frame>4 weeks</time_frame>
    <description>The FAB is a brief tool that discriminates between frontal-temporal type cognitive issues from from Alzheimer's type memory issues. Higher scores are better and scores range from 0-18.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Active Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be receiving active rTMS.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Participants will be receiving sham stimulation with a smaller coil housed within the rTMS device.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>active rTMS</intervention_name>
    <description>rTMS delivers magnetic stimulation to the brain by using an electromagnet to generate a current that can penetrate the scalp and skull.</description>
    <arm_group_label>Active Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Inpatient admission</intervention_name>
    <description>All subjects will be admitted to the hospital for a brief detoxification period followed by 3 weeks of abstinence.</description>
    <arm_group_label>Active Stimulation</arm_group_label>
    <arm_group_label>Sham Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>sham rTMS</intervention_name>
    <description>The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil, and to produce activation of facial muscles similar to the effect of a real H coil, without stimulating the brain itself.</description>
    <arm_group_label>Sham Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Current moderate to severe alcohol use disorder, per DSM-5&#xD;
&#xD;
          2. Use of alcohol which parallels or exceeds the amount alcohol that will be administered&#xD;
             in this study (1 drinking episode per week raising BAL to 0.03 g/dl - approximately 2&#xD;
             drinks within an hour).&#xD;
&#xD;
          3. Age 22-55&#xD;
&#xD;
          4. Able to give informed consent, and comply with study procedures&#xD;
&#xD;
          5. Medically healthy, with the absence of current or past medical or neurological&#xD;
             illnesses (including glaucoma, increased intracranial pressure, liver disease, cardiac&#xD;
             disease, or seizure disorders)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Has a contraindication to MRI, such as magnetically reactive implants, which includes&#xD;
             metal in head except in mouth (cochlear implant, implanted brain stimulators, aneurysm&#xD;
             clips), cardiac pacemakers, implanted neurostimulators and medication pumps, and&#xD;
             intracardiac lines.&#xD;
&#xD;
          2. Substance use disorder with substances other than alcohol or nicotine. The current use&#xD;
             of sedative-hypnotics or opiates will be exclusionary&#xD;
&#xD;
          3. Meets DSM-5 criteria for other psychiatric illness, such as major depression, that&#xD;
             would interfere with participation.&#xD;
&#xD;
          4. History of seizures of any type&#xD;
&#xD;
          5. A family history of epilepsy&#xD;
&#xD;
          6. Taking psychotropic medication that would affect resting motor threshold (such as&#xD;
             anticonvulsants) or increase risk of seizure (especially tricyclic antidepressants of&#xD;
             neuroleptics)&#xD;
&#xD;
          7. Current suicide risk or a history of suicide attempt within the past 2 years&#xD;
&#xD;
          8. Have unstable physical disorders, including those that are previously undiagnosed,&#xD;
             untreated, inadequately treated, or active to an extent which might make participation&#xD;
             hazardous. For example, hypertension (a resting blood pressure &gt; 140/90), heart&#xD;
             failure, a recent history of myocardial infarction, previous stroke, brain lesions,&#xD;
             any history of seizures under any circumstances or low hemoglobin.&#xD;
&#xD;
          9. Currently pregnant&#xD;
&#xD;
         10. History of severe alcohol withdrawal requiring medical care, such as withdrawal&#xD;
             seizures, delirium tremens, withdrawal necessitating medical detoxification.&#xD;
&#xD;
         11. A desire to pursue standard treatment for AUD, such as a rehabilitation program or FDA&#xD;
             approved medications for AUD&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan Wai</last_name>
    <role>Principal Investigator</role>
    <affiliation>New York State Psychiatric Institute</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jonathan Wai, MD</last_name>
    <phone>646-774-7654</phone>
    <email>jonathan.wai@nyspi.columbia.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jonathan Wai</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 9, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>November 3, 2022</last_update_submitted>
  <last_update_submitted_qc>November 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Jonathan Wai</investigator_full_name>
    <investigator_title>Addiction Psychiatry Clinical &amp; Research Fellow</investigator_title>
  </responsible_party>
  <keyword>rTMS</keyword>
  <keyword>alcohol use disorder</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>
  <!-- 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/NCT03809286
org study id: 7691
secondary id: 1K23AA028295
secondary id: 5R21AA026049
nct id: NCT03809286
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The goal of this study is to investigate a treatment approach for alcohol use disorder (AUD)
      using a novel form of brain stimulation called deep repetitive transcranial magnetic
      stimulation (rTMS). The investigators will be targeting frontal regions of the brain that are
      important for memory and decision making. These brain regions have been shown to be impaired
      in patients with AUD. Previous studies have mostly used rTMS to a different frontal brain
      region that is not as deep. These studies have shown that rTMS can reduce craving for
      alcohol, but there is a lack of research showing that rTMS impacts alcohol consumption.
This study aims to examine the effect of rTMS on alcohol drinking behavior in an observed
      laboratory setting. Participants with AUD will be recruited and admitted to the inpatient
      unit for the whole study. After a brief detoxification period, they will receive 3 weeks of
      rTMS while in the research unit. Before and after the 3 weeks of stimulation, participants
      will participate in a decision-making experiment where they can choose to have an alcoholic
      drink or the equivalent amount of money that the drink would cost (alcohol
      self-administration sessions). The investigators will examine their response to alcohol, as
      well as their performance on tasks that relate to impulsivity and memory. Participants will
      also undergo an MRI scan (with spectroscopy) before and after the stimulation period to look
      at changes in the medial prefrontal cortex of the brain. Participants will then meet with a
      study physician for 6 weeks after the study for assessments of alcohol use and medical
      management sessions.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: active vs. sham stimulation
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: double-blind
measure: Change in the choice to self-administer alcohol in the laboratory as assessed by counting the number of drinks consumed in the 2-hour laboratory session.
time frame: 4 weeks
description: Participants will participate in alcohol self-administration sessions in which they are presented with the choice of alcohol or money. The investigators will study the change in choices to choose alcohol during these sessions. There will be one session prior to rTMS and one after 3 weeks of rTMS.
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0.
time frame: 10 weeks
description: Adverse events will be assessed in recorded in accordance with CTCAE v4.0.
measure: Change in craving for alcohol measured using the Alcohol Urge Questionnaire (AUQ).
time frame: 4 weeks
description: This AUQ (Bohn et al. 1995) is an 8-item self report questionnaire where participants rate a seven-point Likert scale with responses ranging from "strongly disagree" to "strongly agree", and a total score is derived from the sum of these items following reverse scoring of two items. A lower score is a better outcome which represents less desire to drink. Scores range from 8-56.
measure: Change in GABA in the mPFC and ACC as measured with magnetic resonance spectroscopy (MRS).
time frame: 4 weeks
description: MRS is performed by using an MRI machine to study metabolites and neurotransmitters in the brain.
measure: Change in abstinence from alcohol following discharge assessed with the Time Line Follow Back Interview.
time frame: 10 weeks
measure: Changes in cognitive control as measured by using the Frontal Assessment Battery (FAB).
time frame: 4 weeks
description: The FAB is a brief tool that discriminates between frontal-temporal type cognitive issues from from Alzheimer's type memory issues. Higher scores are better and scores range from 0-18.
arm group label: Active Stimulation
arm group type: Experimental
description: Participants will be receiving active rTMS.
arm group label: Sham Stimulation
arm group type: Sham Comparator
description: Participants will be receiving sham stimulation with a smaller coil housed within the rTMS device.
intervention type: Device
intervention name: active rTMS
description: rTMS delivers magnetic stimulation to the brain by using an electromagnet to generate a current that can penetrate the scalp and skull.
arm group label: Active Stimulation
intervention type: Behavioral
intervention name: Inpatient admission
description: All subjects will be admitted to the hospital for a brief detoxification period followed by 3 weeks of abstinence.
arm group label: Active Stimulation
arm group label: Sham Stimulation
intervention type: Device
intervention name: sham rTMS
description: The sham coil setting is designed to mimic the auditory artifact and the scalp sensations evoked by the real coil, and to produce activation of facial muscles similar to the effect of a real H coil, without stimulating the brain itself.
arm group label: Sham Stimulation
criteria: 
gender: All
minimum age: 22 Years
maximum age: 55 Years
healthy volunteers: No
last name: Jonathan Wai
role: Principal Investigator
affiliation: New York State Psychiatric Institute
last name: Jonathan Wai, MD
phone: 646-774-7654
email: jonathan.wai@nyspi.columbia.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Jonathan Wai
investigator title: Addiction Psychiatry Clinical & Research Fellow
mesh term: Alcoholism
mesh term: Alcohol Drinking