<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/NCT02223767</url>
  </required_header>
  <id_info>
    <org_study_id>Wuerzburg177/12</org_study_id>
    <secondary_id>098_MH</secondary_id>
    <nct_id>NCT02223767</nct_id>
  </id_info>
  <brief_title>TMS Augmented Exposure Therapy</brief_title>
  <acronym>BEAT</acronym>
  <official_title>Repetitive Transcranial Magnetic Stimulation (rTMS) for Treatment of Height Phobics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wuerzburg University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wuerzburg University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study investigates the beneficial effects of prefrontal brain stimulation (with a&#xD;
      facilitating TMS protocol) before exposure therapy in acrophobic patients. The two exposure&#xD;
      sessions were realized in virtual reality. Before and after therapy, the phobic symptoms were&#xD;
      measured on a subjective, behavioral and physiological level. The placebo-controlled single&#xD;
      blinded study includes 50 phobic patients, which were randomized into verum or sham TMS.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">October 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Subjective Anxiety Symptoms</measure>
    <time_frame>4 weeks</time_frame>
    <description>Change in anxiety questionaire (Agoraphobia Questionaire (AQ), subscale anxiety) from pre (baseline) to post therapy (week 4). The range of the scale is from 0 to 120. Higher values indicate higher anxiety symptoms. For the calculated changes from pre to post this means, that more negative values indicate higher symptom reductions</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subjective Anxiety in Height Situation (BAT), Differences From Pre (Baseline) to Post Therapy (Week 4)</measure>
    <time_frame>4 weeks</time_frame>
    <description>real life anxiety measurement by an behavioral approach test. Ratings on a 0-100 scale. Higher values indicate higher anxiety</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Phobia</condition>
  <arm_group>
    <arm_group_label>Verum transcranial magnetic stimulation (TMS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 Hz TMS over medial prefrontal cortex</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham transcranial magnetic stimulation (TMS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 Hz sham TMS over medial prefrontal cortex</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Experimental: Verum TMS</intervention_name>
    <description>Intensity of 100 % of the resting motor threshold with 10 Hz and intertrial interval (ITI) of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
    <arm_group_label>Verum transcranial magnetic stimulation (TMS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Experimental: Sham TMS</intervention_name>
    <description>Sham stimulation with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
    <arm_group_label>Sham transcranial magnetic stimulation (TMS)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Criteria for a simple phobia: specific heights&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Objective tinnitus Involvement in psychiatric treatments Clinically relevant psychiatric&#xD;
        comorbidity Clinically relevant unstable internal or neurological comorbidity History of or&#xD;
        evidence of significant brain malformation or neoplasm, head injury Cerebral vascular&#xD;
        events Neurodegenerative disorder affecting the brain or prior brain surgery Metal objects&#xD;
        in and around body that can not be removed Pregnancy Alcohol or drug abuse history of&#xD;
        seizures&#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>Martin J. Herrmann, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Würzburg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University hospital</name>
      <address>
        <city>Wuerzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.ppp.ukw.de/beat</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <results_first_submitted>August 30, 2022</results_first_submitted>
  <results_first_submitted_qc>August 1, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 2, 2023</results_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TMS</keyword>
  <keyword>virtual reality (VR)</keyword>
  <keyword>Exposure therapy</keyword>
  <keyword>TMS augmentations of exposure therapy</keyword>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Verum TMS</title>
          <description>10 Hz transcranial magnetic stimulation (TMS) over medial prefrontal cortex&#xD;
Experimental: Verum TMS: Intensity of 100 % of the resting motor threshold with 10 Hz and intertrial interval (ITI) of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
        </group>
        <group group_id="P2">
          <title>Sham TMS</title>
          <description>10 Hz sham TMS over medial prefrontal cortex&#xD;
Experimental: Sham TMS: Sham stimulation with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="19"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Verum TMS</title>
          <description>10 Hz TMS over medial prefrontal cortex&#xD;
Experimental: Verum TMS: Intensity of 100 % of the resting motor threshold with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
        </group>
        <group group_id="B2">
          <title>Sham TMS</title>
          <description>10 Hz sham TMS over medial prefrontal cortex&#xD;
Experimental: Sham TMS: Sham stimulation with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
        </group>
        <group group_id="B3">
          <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="20"/>
            <count group_id="B2" value="19"/>
            <count group_id="B3" value="39"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="43.2" spread="12.6"/>
                    <measurement group_id="B2" value="46.6" spread="13.7"/>
                    <measurement group_id="B3" value="44.9" spread="13.1"/>
                  </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="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </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>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Subjective Anxiety Symptoms</title>
        <description>Change in anxiety questionaire (Agoraphobia Questionaire (AQ), subscale anxiety) from pre (baseline) to post therapy (week 4). The range of the scale is from 0 to 120. Higher values indicate higher anxiety symptoms. For the calculated changes from pre to post this means, that more negative values indicate higher symptom reductions</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Verum TMS</title>
            <description>10 Hz TMS over medial prefrontal cortex&#xD;
Experimental: Verum TMS: Intensity of 100 % of the resting motor threshold with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
          </group>
          <group group_id="O2">
            <title>Sham TMS</title>
            <description>10 Hz sham TMS over medial prefrontal cortex&#xD;
Experimental: Sham TMS: Sham stimulation with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
          </group>
        </group_list>
        <measure>
          <title>Subjective Anxiety Symptoms</title>
          <description>Change in anxiety questionaire (Agoraphobia Questionaire (AQ), subscale anxiety) from pre (baseline) to post therapy (week 4). The range of the scale is from 0 to 120. Higher values indicate higher anxiety symptoms. For the calculated changes from pre to post this means, that more negative values indicate higher symptom reductions</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.4" spread="15.3"/>
                    <measurement group_id="O2" value="7.3" spread="11.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.025</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Subjective Anxiety in Height Situation (BAT), Differences From Pre (Baseline) to Post Therapy (Week 4)</title>
        <description>real life anxiety measurement by an behavioral approach test. Ratings on a 0-100 scale. Higher values indicate higher anxiety</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Verum TMS</title>
            <description>10 Hz TMS over medial prefrontal cortex&#xD;
Experimental: Verum TMS: Intensity of 100 % of the resting motor threshold with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
          </group>
          <group group_id="O2">
            <title>Sham TMS</title>
            <description>10 Hz sham TMS over medial prefrontal cortex&#xD;
Experimental: Sham TMS: Sham stimulation with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
          </group>
        </group_list>
        <measure>
          <title>Subjective Anxiety in Height Situation (BAT), Differences From Pre (Baseline) to Post Therapy (Week 4)</title>
          <description>real life anxiety measurement by an behavioral approach test. Ratings on a 0-100 scale. Higher values indicate higher anxiety</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.8" spread="25.4"/>
                    <measurement group_id="O2" value="16.3" spread="13.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.08</p_value>
            <method>t-test, 1 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 month</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Verum TMS</title>
          <description>10 Hz TMS over medial prefrontal cortex&#xD;
Experimental: Verum TMS: Intensity of 100 % of the resting motor threshold with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
        </group>
        <group group_id="E2">
          <title>Sham TMS</title>
          <description>10 Hz sham TMS over medial prefrontal cortex&#xD;
Experimental: Sham TMS: Sham stimulation with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.</description>
        </group>
      </group_list>
      <serious_events>
        <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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="19"/>
              </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="20"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>neck pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="19"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="20"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="19"/>
              </event>
              <event>
                <sub_title>drowsiness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="19"/>
              </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>Prof. Dr. M Herrmann</name_or_title>
      <organization>Universitätsklinikum Würzburg</organization>
      <phone>093120176650</phone>
      <email>Herrmann_m@ukw.de</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/NCT02223767
org study id: Wuerzburg177/12
secondary id: 098_MH
nct id: NCT02223767
lead sponsor: 
has dmc: No
This study investigates the beneficial effects of prefrontal brain stimulation (with a
      facilitating TMS protocol) before exposure therapy in acrophobic patients. The two exposure
      sessions were realized in virtual reality. Before and after therapy, the phobic symptoms were
      measured on a subjective, behavioral and physiological level. The placebo-controlled single
      blinded study includes 50 phobic patients, which were randomized into verum or sham TMS.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Subjective Anxiety Symptoms
time frame: 4 weeks
description: Change in anxiety questionaire (Agoraphobia Questionaire (AQ), subscale anxiety) from pre (baseline) to post therapy (week 4). The range of the scale is from 0 to 120. Higher values indicate higher anxiety symptoms. For the calculated changes from pre to post this means, that more negative values indicate higher symptom reductions
measure: Subjective Anxiety in Height Situation (BAT), Differences From Pre (Baseline) to Post Therapy (Week 4)
time frame: 4 weeks
description: real life anxiety measurement by an behavioral approach test. Ratings on a 0-100 scale. Higher values indicate higher anxiety
arm group label: Verum transcranial magnetic stimulation (TMS)
arm group type: Experimental
description: 10 Hz TMS over medial prefrontal cortex
arm group label: Sham transcranial magnetic stimulation (TMS)
arm group type: Experimental
description: 10 Hz sham TMS over medial prefrontal cortex
intervention type: Device
intervention name: Experimental: Verum TMS
description: Intensity of 100 % of the resting motor threshold with 10 Hz and intertrial interval (ITI) of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.
arm group label: Verum transcranial magnetic stimulation (TMS)
intervention type: Device
intervention name: Experimental: Sham TMS
description: Sham stimulation with 10 Hz and ITI of 26 s. 1560 pulse in 40 trains at all . One train lasts 4 s.
arm group label: Sham transcranial magnetic stimulation (TMS)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Martin J. Herrmann, PhD
role: Principal Investigator
affiliation: University of Würzburg
facility: 
country: Germany
url: http://www.ppp.ukw.de/beat
description: Related Info
responsible party type: Sponsor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 