<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/NCT03027414</url>
  </required_header>
  <id_info>
    <org_study_id>170042</org_study_id>
    <secondary_id>17-M-0042</secondary_id>
    <nct_id>NCT03027414</nct_id>
  </id_info>
  <brief_title>Effect of Transcranial Magnetic Stimulation to the Frontoparietal Attention Network on Anxiety Potentiated Startle</brief_title>
  <official_title>The Effect of Transcranial Magnetic Stimulation to the Frontoparietal Attention Network on Anxiety Potentiated Startle</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Researchers want to better understand brain processes related to fear and anxiety. They want&#xD;
      to find out if transcranial magnetic stimulation (TMS), a type of brain stimulation, can&#xD;
      reduce anxiety.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To see how TMS affects fear and anxiety through memory and attention tasks.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Healthy people ages 18-50 who are right-handed&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened through another protocol.&#xD;
&#xD;
      Participants in the pilot study will have 1 visit. This includes:&#xD;
&#xD;
      Urine tests&#xD;
&#xD;
      Questionnaires about mood and thinking&#xD;
&#xD;
      Shock and startle workup: Electrodes are taped to the wrists or fingers. Participants will be&#xD;
      shocked to find out what level of shock is uncomfortable but tolerable. They will hear loud,&#xD;
      sudden noises through headphones.&#xD;
&#xD;
      TMS: A coil is held on the scalp. A magnetic field stimulates the brain. Sometimes they might&#xD;
      receive fake TMS. This feels the same as real TMS. They will perform simple tasks.&#xD;
      Participants in the main study will have 2 visits within 2 weeks.&#xD;
&#xD;
      The first visit includes:&#xD;
&#xD;
      Urine tests&#xD;
&#xD;
      Questionnaires about mood and thinking&#xD;
&#xD;
      MRI: Participants lie on a table that slides into a scanner. They will be in the scanner&#xD;
      about 1 hour. A computer screen in the scanner will tell them to perform simple tasks.&#xD;
&#xD;
      The second visit includes:&#xD;
&#xD;
      Shock and startle workup&#xD;
&#xD;
      TMS&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective: To determine the effect of non-invasive brain stimulation on anxiety and&#xD;
      anxiety-cognition interactions in healthy subjects. Toward this aim we will test the effect&#xD;
      of transcranial magnetic stimulation (TMS) on two outcome measures: 1) Fear and anxiety&#xD;
      during the threat of predictable and unpredictable shock (NPU threat test; Substudies 1 and&#xD;
      3), and 2) Working memory (WM) related anxiety downregulation while performing the Sternberg&#xD;
      WM task under threat of shock (Substudy 2).&#xD;
&#xD;
      Study population: The study population will consist of up to 184 healthy volunteers between&#xD;
      the ages of 18-50.&#xD;
&#xD;
      Design: This study will consists of two (sub-studies 1 and 2) or three (sub-study 3)&#xD;
      outpatient visits (1 MRI, 1 or 2 TMS visits [2 for sub-study 3]). In this protocol we will&#xD;
      explore the effect of TMS in three sub-studies in the TMS study visit. The sub-studies will&#xD;
      contain either the NPU or the Sternberg task during the TMS visits. The first visit (MRI)&#xD;
      will consist of the same procedures for all sub-studies. Each subject will be assigned to&#xD;
      only one of the sub-studies.&#xD;
&#xD;
      Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal&#xD;
      attention network during the Sternberg WM task. Subjects will have to maintain a series of&#xD;
      letters in WM for a brief interval during blocks of safety and threat of shock.&#xD;
&#xD;
      NPU Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention&#xD;
      network during the NPU threat test. Subjects will be exposed to blocks in which they are&#xD;
      either 1) safe from shock (neutral), 2) at risk of shock delivered only during a cue&#xD;
      (predictable), or 3) at risk of shock presented randomly (unpredictable).&#xD;
&#xD;
      Outcome measures: In both studies the primary outcome measure will be anxiety-potentiated&#xD;
      startle (APS), which is the increase in startle magnitude during periods of threat compared&#xD;
      to periods of safety. We expect active, but not sham TMS to increase activity in the dlPFC,&#xD;
      and therefore reduce APS in both studies&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 23, 2017</start_date>
  <completion_date type="Actual">June 29, 2020</completion_date>
  <primary_completion_date type="Actual">July 19, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Anxiety-potentiated Startle</measure>
    <time_frame>Pre and post stimulation</time_frame>
    <description>Electromyography Facial electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle at 2000 Hz using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm hydrogel coated vinyl electrodes (Rhythmlink #DECUS10026; Columbia, SC).&#xD;
Startle EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = [Zx × 10] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD &gt; 2x run SD) were excluded, and &quot;no blink&quot; (peak &lt; baseline range) trials were coded as 0. To calculate APS, we subtracted the response during the neutral ITI from the response during the unpredictable ITI.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Working Memory (WM) Related Anxiety Downregulation While Performing the Sternberg WM Task Under Threat of Shock.</measure>
    <time_frame>Pre and post stimulation</time_frame>
    <description>Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the Sternberg WM task. Subjects will have to maintain a series of letters in WM for a brief interval during blocks of safety and threat of shock.&#xD;
Electromyography Facial electromyography (EMG) startle responses are recorded from the left orbicularis oculi muscle at 2000 Hz.&#xD;
Startle EMG is bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses are scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores (tx = [Zx × 10] + 50). Noisy trials (baseline SD &gt; 2x run SD) are excluded, and &quot;no blink&quot; (peak &lt; baseline range) trials are coded as 0. These t scores are then averaged across trials within each condition, and threat-safe contrasts are calculated independently for each level of load (low vs. high) and timing (maintenance vs. ITI).</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Substudy 1 Active and Sham</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HVs that receive TMS over the right dlPFC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Substudy 2 Active and Sham</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HVs that receive TMS over the right dlFPC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Substudy 3 Active and Sham</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HVs will receive offline TMS to the lest IPS (FPN)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Transcranial Magnetic Stimulation Sham</intervention_name>
    <description>TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
    <arm_group_label>Substudy 1 Active and Sham</arm_group_label>
    <arm_group_label>Substudy 2 Active and Sham</arm_group_label>
    <arm_group_label>Substudy 3 Active and Sham</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Magnetic Stimulation</intervention_name>
    <description>TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
    <arm_group_label>Substudy 1 Active and Sham</arm_group_label>
    <arm_group_label>Substudy 2 Active and Sham</arm_group_label>
    <arm_group_label>Substudy 3 Active and Sham</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Ages 18-50&#xD;
&#xD;
          -  Subjects able to give their consent&#xD;
&#xD;
          -  Right handed&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Non-English speaking individual&#xD;
&#xD;
          -  Any significant medical or neurological problems (e.g. cardiovascular illness,&#xD;
             respiratory illness, neurological illness, seizure, etc.)&#xD;
&#xD;
          -  Current or past Axis I psychiatric disorder(s) as identified with the Structured&#xD;
             Clinical Interview for DSM-IV, non-patient edition (SCID-np)&#xD;
&#xD;
          -  Active or history of active suicidal ideation.&#xD;
&#xD;
          -  Evidence of a first-degree relative with history of psychosis or bipolar disorder;&#xD;
             specifically, participant will know diagnosis or treatment in order to confirm&#xD;
             presence of disorder.&#xD;
&#xD;
          -  Alcohol/drug problems in the past year or lifetime alcohol or drug dependence&#xD;
             according to the Structured Clinical Interview for DSM-IV.&#xD;
&#xD;
          -  Current use of medications that act on histamine (i.e. diphenhydramine), dopamine&#xD;
             (methylphenidate), norepinephrine (buproprion), serotonin (sertraline), or&#xD;
             acetylcholine (amitryptiline) receptors. Subjects will be excluded on this basis if&#xD;
             they either 1) take these medications on a chronic basis, or 2) if they have taken the&#xD;
             drug within 5 half-lives of the drug metabolism, determined by the medical&#xD;
             professional at the time of screening.&#xD;
&#xD;
          -  History of seizure (childhood febrile seizures are acceptable and these subjects may&#xD;
             be included in the study),&#xD;
&#xD;
          -  History of epilepsy in self or first degree relatives, stroke, brain surgery, head&#xD;
             injury, cranial metal implants, known structural brain lesion.&#xD;
&#xD;
          -  Increased risk of seizure for any reason, including prior diagnosis of increased&#xD;
             intracranial pressure (such as after large infarctions or trauma), or currently taking&#xD;
             medication that lowers the seizure threshold (table below).&#xD;
&#xD;
          -  Pregnancy, or positive pregnancy test.&#xD;
&#xD;
          -  Neurological syndrome of the arm (e.g., carpal tunnel syndrome, cubital tunnel&#xD;
             syndrome, etc.)&#xD;
&#xD;
          -  Positive urine toxicology screen during the screening visit.&#xD;
&#xD;
          -  IQ &lt;80&#xD;
&#xD;
          -  Employee or staff of NIMH or are an immediate family member of a NIMH employee, staff,&#xD;
             or NIMH contractors.&#xD;
&#xD;
          -  Allergy to lidocaine or topical anesthetics (participants in sub-study 3 only).&#xD;
&#xD;
          -  Any medical condition that increases risk for fMRI or TMS:&#xD;
&#xD;
               -  Any metal in their body which would make having an MRI scan unsafe, such as&#xD;
                  pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial&#xD;
                  heart valves, cochlear implants or shrapnel fragments, or if you were a welder or&#xD;
                  metal worker, since you may small metal fragments in the eye.&#xD;
&#xD;
               -  Participants who are uncomfortable in small closed spaces (have claustrophobia)&#xD;
                  and would feel uncomfortable in the MRI machine&#xD;
&#xD;
               -  Patients who have difficulty lying flat on their back for up to 60 min in the&#xD;
                  scanner&#xD;
&#xD;
               -  History of hearing loss&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christian Grillon, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Mental Health (NIMH)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-M-0042.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Balderston NL, Quispe-Escudero D, Hale E, Davis A, O'Connell K, Ernst M, Grillon C. Working memory maintenance is sufficient to reduce state anxiety. Psychophysiology. 2016 Nov;53(11):1660-1668. doi: 10.1111/psyp.12726. Epub 2016 Jul 19.</citation>
    <PMID>27434207</PMID>
  </reference>
  <reference>
    <citation>Schmitz A, Grillon C. Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test). Nat Protoc. 2012 Feb 23;7(3):527-32. doi: 10.1038/nprot.2012.001.</citation>
    <PMID>22362158</PMID>
  </reference>
  <reference>
    <citation>Slotema CW, Blom JD, Hoek HW, Sommer IE. Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry. 2010 Jul;71(7):873-84. doi: 10.4088/JCP.08m04872gre. Epub 2010 Mar 9.</citation>
    <PMID>20361902</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>January 18, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <results_first_submitted>July 23, 2021</results_first_submitted>
  <results_first_submitted_qc>April 27, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">May 17, 2022</results_first_posted>
  <last_update_submitted>April 27, 2022</last_update_submitted>
  <last_update_submitted_qc>April 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anxiety</keyword>
  <keyword>Startle</keyword>
  <keyword>Dorsolateral Prefrontal Cortex</keyword>
  <keyword>Transcranial Magnetic Stimulation (TMS)</keyword>
  <keyword>Working Memory</keyword>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03027414/Prot_SAP_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03027414/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Substudy 1 Active and Sham</title>
          <description>HVs that receive active and sham TMS over the right dlPFC&#xD;
Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
        <group group_id="P2">
          <title>Substudy 2 Active and Sham</title>
          <description>HVs that receive active and sham TMS over the right dlPFC&#xD;
Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
        <group group_id="P3">
          <title>Substudy 3 Active and Sham</title>
          <description>HVs will receive offline TMS to the lest IPS (FPN)&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>No participants were recruited in Substudy 2. Study was stopped because lead investigator (Dr. Balderston) changed position prior to the initiation of Study 2</population>
      <group_list>
        <group group_id="B1">
          <title>Substudy 1 Active and Sham</title>
          <description>HVs that receive active and Sham TMS over the right dlPFC&#xD;
Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
        <group group_id="B2">
          <title>Substudy 2 Active and Sham</title>
          <description>HVs that receive active and Sham TMS over the right dlPFC&#xD;
Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
        <group group_id="B3">
          <title>Substudy 3 Active and Sham</title>
          <description>HVs will receive offline TMS to the lest IPS (FPN)&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="28"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="26"/>
            <count group_id="B4" value="54"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B3" value="26"/>
                    <measurement group_id="B4" value="54"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27.25" spread="7.414392375"/>
                    <measurement group_id="B3" value="30.46153846" spread="8.52701936"/>
                    <measurement group_id="B4" value="28.7962963" spread="8.129460894"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="47"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B3" value="26"/>
                    <measurement group_id="B4" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Anxiety-potentiated Startle</title>
        <description>Electromyography Facial electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle at 2000 Hz using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm hydrogel coated vinyl electrodes (Rhythmlink #DECUS10026; Columbia, SC).&#xD;
Startle EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = [Zx × 10] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD &gt; 2x run SD) were excluded, and &quot;no blink&quot; (peak &lt; baseline range) trials were coded as 0. To calculate APS, we subtracted the response during the neutral ITI from the response during the unpredictable ITI.</description>
        <time_frame>Pre and post stimulation</time_frame>
        <population>Healthy Volunteers</population>
        <group_list>
          <group group_id="O1">
            <title>Substudy 1 Active and Sham</title>
            <description>HVs that receive active and sham TMS over the right dlPFC&#xD;
Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
          </group>
          <group group_id="O2">
            <title>Substudy 3 Active and Sham</title>
            <description>HVs will receive offline TMS to the lest IPS (FPN)&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Anxiety-potentiated Startle</title>
          <description>Electromyography Facial electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle at 2000 Hz using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm hydrogel coated vinyl electrodes (Rhythmlink #DECUS10026; Columbia, SC).&#xD;
Startle EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = [Zx × 10] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD &gt; 2x run SD) were excluded, and &quot;no blink&quot; (peak &lt; baseline range) trials were coded as 0. To calculate APS, we subtracted the response during the neutral ITI from the response during the unpredictable ITI.</description>
          <population>Healthy Volunteers</population>
          <units>T-scores</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Active</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.032164105" spread="1.31706568"/>
                    <measurement group_id="O2" value="2.420193836" spread="1.174992336"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sham</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.412441384" spread="1.02011584"/>
                    <measurement group_id="O2" value="4.467812115" spread="0.966471881"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No TMS / Pre-stimulation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.832028871" spread="0.989278736"/>
                    <measurement group_id="O2" value="4.960918182" spread="1.111076546"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Working Memory (WM) Related Anxiety Downregulation While Performing the Sternberg WM Task Under Threat of Shock.</title>
        <description>Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the Sternberg WM task. Subjects will have to maintain a series of letters in WM for a brief interval during blocks of safety and threat of shock.&#xD;
Electromyography Facial electromyography (EMG) startle responses are recorded from the left orbicularis oculi muscle at 2000 Hz.&#xD;
Startle EMG is bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses are scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores (tx = [Zx × 10] + 50). Noisy trials (baseline SD &gt; 2x run SD) are excluded, and &quot;no blink&quot; (peak &lt; baseline range) trials are coded as 0. These t scores are then averaged across trials within each condition, and threat-safe contrasts are calculated independently for each level of load (low vs. high) and timing (maintenance vs. ITI).</description>
        <time_frame>Pre and post stimulation</time_frame>
        <population>No participants were recruited in Substudy 2. Study was stopped because lead investigator (Dr. Balderston) changed position prior to the initiation of Study 2</population>
        <group_list>
          <group group_id="O1">
            <title>Substudy 2</title>
            <description>HVs that receive TMS over the right dlFPC&#xD;
Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
          </group>
        </group_list>
        <measure>
          <title>Working Memory (WM) Related Anxiety Downregulation While Performing the Sternberg WM Task Under Threat of Shock.</title>
          <description>Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the Sternberg WM task. Subjects will have to maintain a series of letters in WM for a brief interval during blocks of safety and threat of shock.&#xD;
Electromyography Facial electromyography (EMG) startle responses are recorded from the left orbicularis oculi muscle at 2000 Hz.&#xD;
Startle EMG is bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses are scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores (tx = [Zx × 10] + 50). Noisy trials (baseline SD &gt; 2x run SD) are excluded, and &quot;no blink&quot; (peak &lt; baseline range) trials are coded as 0. These t scores are then averaged across trials within each condition, and threat-safe contrasts are calculated independently for each level of load (low vs. high) and timing (maintenance vs. ITI).</description>
          <population>No participants were recruited in Substudy 2. Study was stopped because lead investigator (Dr. Balderston) changed position prior to the initiation of Study 2</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>During study participation, which typically lasted less than 1 month.</time_frame>
      <desc>The Principal Investigator was responsible for detecting, documenting, and reporting unanticipated problems, adverse events (AEs), including serious adverse events (SAEs), and deviations in accordance with NIH policy, IRB requirements, and federal regulations. Relatedness to the research of all serious adverse events will be determined by the PI in consultation with the CD.</desc>
      <group_list>
        <group group_id="E1">
          <title>Substudy 1 Active and Sham</title>
          <description>HVs that receive active and Sham TMS over the right dlPFC&#xD;
Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
        <group group_id="E2">
          <title>Substudy 2 Active and Sham</title>
          <description>HVs that receive active and Sham TMS over the right dlPFC&#xD;
Transcranial Magnetic Stimulation Sham: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
        <group group_id="E3">
          <title>Substudy 3</title>
          <description>HVs will receive offline TMS to the lest IPS (FPN)&#xD;
Transcranial Magnetic Stimulation: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>Possible vasovagal syncope</sub_title>
                <description>Unexpected adverse event</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Product Issues</title>
            <event_list>
              <event>
                <sub_title>mild headache</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>scalp or face discomfort</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>non-medical device malfunction</sub_title>
                <description>computer malfunction resulting in mild unexpected shock presentation</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Nicholas Balderston</name_or_title>
      <organization>University of Pennsylvania</organization>
      <phone>2157463058</phone>
      <email>nicholas.balderston@pennmedicine.upenn.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03027414
org study id: 170042
secondary id: 17-M-0042
nct id: NCT03027414
lead sponsor: 
is fda regulated drug: No
is fda regulated device: Yes
Background:

      Researchers want to better understand brain processes related to fear and anxiety. They want
      to find out if transcranial magnetic stimulation (TMS), a type of brain stimulation, can
      reduce anxiety.

      Objective:

      To see how TMS affects fear and anxiety through memory and attention tasks.

      Eligibility:

      Healthy people ages 18-50 who are right-handed

      Design:

      Participants will be screened through another protocol.

      Participants in the pilot study will have 1 visit. This includes:

      Urine tests

      Questionnaires about mood and thinking

      Shock and startle workup: Electrodes are taped to the wrists or fingers. Participants will be
      shocked to find out what level of shock is uncomfortable but tolerable. They will hear loud,
      sudden noises through headphones.

      TMS: A coil is held on the scalp. A magnetic field stimulates the brain. Sometimes they might
      receive fake TMS. This feels the same as real TMS. They will perform simple tasks.
      Participants in the main study will have 2 visits within 2 weeks.

      The first visit includes:

      Urine tests

      Questionnaires about mood and thinking

      MRI: Participants lie on a table that slides into a scanner. They will be in the scanner
      about 1 hour. A computer screen in the scanner will tell them to perform simple tasks.

      The second visit includes:

      Shock and startle workup

      TMS
Objective: To determine the effect of non-invasive brain stimulation on anxiety and
      anxiety-cognition interactions in healthy subjects. Toward this aim we will test the effect
      of transcranial magnetic stimulation (TMS) on two outcome measures: 1) Fear and anxiety
      during the threat of predictable and unpredictable shock (NPU threat test; Substudies 1 and
      3), and 2) Working memory (WM) related anxiety downregulation while performing the Sternberg
      WM task under threat of shock (Substudy 2).

      Study population: The study population will consist of up to 184 healthy volunteers between
      the ages of 18-50.

      Design: This study will consists of two (sub-studies 1 and 2) or three (sub-study 3)
      outpatient visits (1 MRI, 1 or 2 TMS visits [2 for sub-study 3]). In this protocol we will
      explore the effect of TMS in three sub-studies in the TMS study visit. The sub-studies will
      contain either the NPU or the Sternberg task during the TMS visits. The first visit (MRI)
      will consist of the same procedures for all sub-studies. Each subject will be assigned to
      only one of the sub-studies.

      Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal
      attention network during the Sternberg WM task. Subjects will have to maintain a series of
      letters in WM for a brief interval during blocks of safety and threat of shock.

      NPU Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention
      network during the NPU threat test. Subjects will be exposed to blocks in which they are
      either 1) safe from shock (neutral), 2) at risk of shock delivered only during a cue
      (predictable), or 3) at risk of shock presented randomly (unpredictable).

      Outcome measures: In both studies the primary outcome measure will be anxiety-potentiated
      startle (APS), which is the increase in startle magnitude during periods of threat compared
      to periods of safety. We expect active, but not sham TMS to increase activity in the dlPFC,
      and therefore reduce APS in both studies
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Anxiety-potentiated Startle
time frame: Pre and post stimulation
description: Electromyography Facial electromyography (EMG) startle responses were recorded from the left orbicularis oculi muscle at 2000 Hz using a Biopac MP160 unit (Biopac; Goleta, CA) via 15 × 20 mm hydrogel coated vinyl electrodes (Rhythmlink #DECUS10026; Columbia, SC).
Startle EMG was bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses were scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores with a mean of 50 and a standard deviation of 10 (tx = [Zx × 10] + 50). Greater t-scores mean larger blinks, which could be associated with greater anxiety, however there is no clinically relevent threshold. Noisy trials (baseline SD > 2x run SD) were excluded, and "no blink" (peak < baseline range) trials were coded as 0. To calculate APS, we subtracted the response during the neutral ITI from the response during the unpredictable ITI.
measure: Working Memory (WM) Related Anxiety Downregulation While Performing the Sternberg WM Task Under Threat of Shock.
time frame: Pre and post stimulation
description: Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention network during the Sternberg WM task. Subjects will have to maintain a series of letters in WM for a brief interval during blocks of safety and threat of shock.
Electromyography Facial electromyography (EMG) startle responses are recorded from the left orbicularis oculi muscle at 2000 Hz.
Startle EMG is bandpass filtered from 30 to 300 Hz, rectified, and smoothed using a 20-ms sliding window. Startle responses are scored as the peak (max during the 20 ms to 120 ms post-noise window) - the baseline (50 ms pre-noise window), and converted to t-scores (tx = [Zx × 10] + 50). Noisy trials (baseline SD > 2x run SD) are excluded, and "no blink" (peak < baseline range) trials are coded as 0. These t scores are then averaged across trials within each condition, and threat-safe contrasts are calculated independently for each level of load (low vs. high) and timing (maintenance vs. ITI).
arm group label: Substudy 1 Active and Sham
arm group type: Experimental
description: HVs that receive TMS over the right dlPFC
arm group label: Substudy 2 Active and Sham
arm group type: Experimental
description: HVs that receive TMS over the right dlFPC
arm group label: Substudy 3 Active and Sham
arm group type: Experimental
description: HVs will receive offline TMS to the lest IPS (FPN)
intervention type: Drug
intervention name: Transcranial Magnetic Stimulation Sham
description: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
arm group label: Substudy 1 Active and Sham
arm group label: Substudy 2 Active and Sham
arm group label: Substudy 3 Active and Sham
intervention type: Device
intervention name: Transcranial Magnetic Stimulation
description: TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
arm group label: Substudy 1 Active and Sham
arm group label: Substudy 2 Active and Sham
arm group label: Substudy 3 Active and Sham
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Christian Grillon, Ph.D.
role: Principal Investigator
affiliation: National Institute of Mental Health (NIMH)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-M-0042.html
description: NIH Clinical Center Detailed Web Page
citation: Balderston NL, Quispe-Escudero D, Hale E, Davis A, O'Connell K, Ernst M, Grillon C. Working memory maintenance is sufficient to reduce state anxiety. Psychophysiology. 2016 Nov;53(11):1660-1668. doi: 10.1111/psyp.12726. Epub 2016 Jul 19.
PMID: 27434207
citation: Schmitz A, Grillon C. Assessing fear and anxiety in humans using the threat of predictable and unpredictable aversive events (the NPU-threat test). Nat Protoc. 2012 Feb 23;7(3):527-32. doi: 10.1038/nprot.2012.001.
PMID: 22362158
citation: Slotema CW, Blom JD, Hoek HW, Sommer IE. Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry. 2010 Jul;71(7):873-84. doi: 10.4088/JCP.08m04872gre. Epub 2010 Mar 9.
PMID: 20361902
responsible party type: Sponsor
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 