<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/NCT01702948</url>
  </required_header>
  <id_info>
    <org_study_id>999912479</org_study_id>
    <secondary_id>12-DA-N479</secondary_id>
    <nct_id>NCT01702948</nct_id>
  </id_info>
  <brief_title>Studying Nicotine Addiction With Transcranial Magnetic Stimulation</brief_title>
  <official_title>Understanding the Neurocircuitry of Nicotine Addiction Using Repetitive Transcranial Magnetic Stimulation (rTMS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      - Nicotine addiction often makes it difficult to stop smoking. Researchers want to understand&#xD;
      the areas of the brain that are important in nicotine addiction. They will use a type of&#xD;
      brain stimulation called repetitive transcranial magnetic stimulation (rTMS) to look at part&#xD;
      of the brain that may be involved in nicotine addiction. They will see how these areas affect&#xD;
      brain function, thinking, and decision making. For this study, rTMS will first be tested on&#xD;
      nonsmokers, then smokers will be recruited at a later time.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      - To study areas of the brain involved in nicotine addiction.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      - Individuals at least 18 years of age who do not smoke.&#xD;
&#xD;
      Design:&#xD;
&#xD;
        -  Participants will be screened with a physical exam and medical history. They will also&#xD;
           provide a urine sample.&#xD;
&#xD;
        -  There will be four study sessions. The first session will involve a magnetic resonance&#xD;
           imaging (MRI) scan. The other three visits will involve rTMS and MRI scans.&#xD;
&#xD;
        -  The first MRI scan will take a baseline picture of the brain. Participants will also&#xD;
           practice the tasks for the other three sessions in a mock scanner.&#xD;
&#xD;
        -  At the next three visits, participants will have rTMS and MRI scans. Two visits will&#xD;
           involve rTMS; the other visit will involve mock rTMS with no actual magnetic&#xD;
           stimulation. During the MRI scans, participants will perform tasks that involve decision&#xD;
           making.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective: To investigate the neurocircuitry cognitive and affective processing relevant to&#xD;
      nicotine addiction using repetitive Transcranial Magnetic Stimulation (rTMS). Specifically,&#xD;
      we will examine insula neurocircuitry using a unilateral H-coil to deliver rTMS to the Right&#xD;
      dorsolateral prefrontal cortex (R DLPFC) and insula. We will examine the effect of various&#xD;
      stimulation parameters on behavior as well as on task based activation and resting state&#xD;
      functional connectivity (rsFC) during fMRI scanning.&#xD;
&#xD;
      Study population: Up to 60 healthy adults who are non-smokers will be enrolled to achieve 28&#xD;
      completers.&#xD;
&#xD;
      Design: Within subject design with each subject completing 4 sessions: rTMS at two different&#xD;
      stimulation frequencies and 2 sham sessions.&#xD;
&#xD;
      Outcome measures: Behavior on a decision making task and task based and resting state blood&#xD;
      oxygen level-dependent (BOLD) activation in neural circuits relevant to nicotine addiction&#xD;
      during fMRI scanning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 10, 2012</start_date>
  <completion_date>October 3, 2017</completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Behavior on a decision making task and task based and resting state BOLD activation in neural circuits relevant to nicotine addiction during fMRI scanning.</measure>
  </primary_outcome>
  <enrollment type="Actual">46</enrollment>
  <condition>Nicotine Dependence</condition>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. Males and females 18 - 55 years of age&#xD;
&#xD;
               2. Able to give valid informed consent&#xD;
&#xD;
               3. Right-handed&#xD;
&#xD;
               4. If the subject is female, of childbearing potential, and sexually active, she&#xD;
                  agrees to use a medically acceptable contraception, and not become pregnant for&#xD;
                  the duration of the study. A woman is considered of childbearing potential unless&#xD;
                  post-menopausal or surgically sterilized. Female patients of childbearing&#xD;
                  potential who are or who anticipate the possibility of becoming sexually active&#xD;
                  with a male partner must use either: (1) contraceptive pill or intrauterine&#xD;
                  device (IUD) or depot hormonal preparation (ring, injection implant); and/or (2)&#xD;
                  a barrier method of contraception such as diaphragm, sponge with spermicide, or&#xD;
                  condom. Women who are not sexually active do not have to agree to use one of the&#xD;
                  acceptable contraception methods. Contraceptive measures will be reviewed with&#xD;
                  female subjects at each visit prior to the TMS session.&#xD;
&#xD;
        EXCLUSION CRITERIA:&lt;TAB&gt;&#xD;
&#xD;
          1. Personal or first-degree family history of any clinically defined neurological&#xD;
             disorder, including organic brain disease, epilepsy, stroke, brain lesions, multiple&#xD;
             sclerosis, previous neurosurgery, or personal history of head trauma that resulted in&#xD;
             loss of consciousness.&#xD;
&#xD;
          2. Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted&#xD;
             medication pumps, intracardiac lines, or acute, unstable cardiac disease, with&#xD;
             intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or&#xD;
             electrodes) or any other metal object within or near the head that cannot be safely&#xD;
             removed.&#xD;
&#xD;
          3. Current use, or use in the past 4 weeks of any investigational drug or of any&#xD;
             medications with psychotropic, anti or pro-convulsive action&#xD;
&#xD;
          4. Increased intracranial pressure (lowers seizure threshold)&#xD;
&#xD;
          5. Lifetime history of major depressive disorder, schizophrenia, bipolar disorder, mania,&#xD;
             or hypomania or current substance abuse or dependence or past dependence by DSM IV&#xD;
             criteria, or urine toxicology positive for any illicit substance.&#xD;
&#xD;
          6. History of myocardial infarction, angina, congestive heart failure, cardiomyopathy,&#xD;
             stroke or transient ischemic attack, or any heart condition currently under medical&#xD;
             care.&#xD;
&#xD;
          7. Pregnant or nursing women or women with reproductive potential who are sexually active&#xD;
             and not using an acceptable form of contraception.&#xD;
&#xD;
          8. Any history of seizure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mary R Lee, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institute on Drug Abuse</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM. Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia. J Neurol. 2012 Jan;259(1):83-92. doi: 10.1007/s00415-011-6128-4. Epub 2011 Jun 14.</citation>
    <PMID>21671144</PMID>
  </reference>
  <reference>
    <citation>Baeken C, De Raedt R, Van Schuerbeek P, Vanderhasselt MA, De Mey J, Bossuyt A, Luypaert R. Right prefrontal HF-rTMS attenuates right amygdala processing of negatively valenced emotional stimuli in healthy females. Behav Brain Res. 2010 Dec 25;214(2):450-5. doi: 10.1016/j.bbr.2010.06.029. Epub 2010 Jul 1.</citation>
    <PMID>20600336</PMID>
  </reference>
  <reference>
    <citation>Baumgartner T, Knoch D, Hotz P, Eisenegger C, Fehr E. Dorsolateral and ventromedial prefrontal cortex orchestrate normative choice. Nat Neurosci. 2011 Oct 2;14(11):1468-74. doi: 10.1038/nn.2933.</citation>
    <PMID>21964488</PMID>
  </reference>
  <verification_date>October 3, 2017</verification_date>
  <study_first_submitted>October 6, 2012</study_first_submitted>
  <study_first_submitted_qc>October 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2012</study_first_posted>
  <last_update_submitted>December 4, 2019</last_update_submitted>
  <last_update_submitted_qc>December 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2019</last_update_posted>
  <keyword>Functional Magnetic Resonance Imaging (fMRI)</keyword>
  <keyword>Nicotine</keyword>
  <keyword>Repetitive TMS (rTMS)</keyword>
  <keyword>fMRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</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/NCT01702948
org study id: 999912479
secondary id: 12-DA-N479
nct id: NCT01702948
lead sponsor: 
Background:

      - Nicotine addiction often makes it difficult to stop smoking. Researchers want to understand
      the areas of the brain that are important in nicotine addiction. They will use a type of
      brain stimulation called repetitive transcranial magnetic stimulation (rTMS) to look at part
      of the brain that may be involved in nicotine addiction. They will see how these areas affect
      brain function, thinking, and decision making. For this study, rTMS will first be tested on
      nonsmokers, then smokers will be recruited at a later time.

      Objectives:

      - To study areas of the brain involved in nicotine addiction.

      Eligibility:

      - Individuals at least 18 years of age who do not smoke.

      Design:

        -  Participants will be screened with a physical exam and medical history. They will also
           provide a urine sample.

        -  There will be four study sessions. The first session will involve a magnetic resonance
           imaging (MRI) scan. The other three visits will involve rTMS and MRI scans.

        -  The first MRI scan will take a baseline picture of the brain. Participants will also
           practice the tasks for the other three sessions in a mock scanner.

        -  At the next three visits, participants will have rTMS and MRI scans. Two visits will
           involve rTMS; the other visit will involve mock rTMS with no actual magnetic
           stimulation. During the MRI scans, participants will perform tasks that involve decision
           making.
Objective: To investigate the neurocircuitry cognitive and affective processing relevant to
      nicotine addiction using repetitive Transcranial Magnetic Stimulation (rTMS). Specifically,
      we will examine insula neurocircuitry using a unilateral H-coil to deliver rTMS to the Right
      dorsolateral prefrontal cortex (R DLPFC) and insula. We will examine the effect of various
      stimulation parameters on behavior as well as on task based activation and resting state
      functional connectivity (rsFC) during fMRI scanning.

      Study population: Up to 60 healthy adults who are non-smokers will be enrolled to achieve 28
      completers.

      Design: Within subject design with each subject completing 4 sessions: rTMS at two different
      stimulation frequencies and 2 sham sessions.

      Outcome measures: Behavior on a decision making task and task based and resting state blood
      oxygen level-dependent (BOLD) activation in neural circuits relevant to nicotine addiction
      during fMRI scanning.
time perspective: Retrospective
measure: Behavior on a decision making task and task based and resting state BOLD activation in neural circuits relevant to nicotine addiction during fMRI scanning.
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mary R Lee, M.D.
role: Principal Investigator
affiliation: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
facility: 
country: United States
citation: Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM. Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia. J Neurol. 2012 Jan;259(1):83-92. doi: 10.1007/s00415-011-6128-4. Epub 2011 Jun 14.
PMID: 21671144
citation: Baeken C, De Raedt R, Van Schuerbeek P, Vanderhasselt MA, De Mey J, Bossuyt A, Luypaert R. Right prefrontal HF-rTMS attenuates right amygdala processing of negatively valenced emotional stimuli in healthy females. Behav Brain Res. 2010 Dec 25;214(2):450-5. doi: 10.1016/j.bbr.2010.06.029. Epub 2010 Jul 1.
PMID: 20600336
citation: Baumgartner T, Knoch D, Hotz P, Eisenegger C, Fehr E. Dorsolateral and ventromedial prefrontal cortex orchestrate normative choice. Nat Neurosci. 2011 Oct 2;14(11):1468-74. doi: 10.1038/nn.2933.
PMID: 21964488
mesh term: Tobacco Use Disorder