<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/NCT03275766</url>
  </required_header>
  <id_info>
    <org_study_id>SNCTP610</org_study_id>
    <nct_id>NCT03275766</nct_id>
  </id_info>
  <brief_title>Transcranial Magnetic Stimulation (TMS) for Motor Symptoms in Psychiatric Disorders</brief_title>
  <official_title>Effects of Transcranial Magnetic Stimulation on Motor Symptoms of Patients With Psychiatric Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Bern</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Bern</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Psychomotor slowing may occur in major psychiatric disorders, such as major depressive&#xD;
      disorders or schizophrenia spectrum disorders. It refers to slowing of fine motor skills,&#xD;
      motor planning and gross motor behavior. In major depression and schizophrenia, psychomotor&#xD;
      slowing is associated with alterations of premotor cortex, dorsolateral prefrontal cortex and&#xD;
      basal ganglia. This randomized, sham-controlled, prospective trial will test, whether 15&#xD;
      sessions of repetitive transcranial magnetic stimulation (rTMS) may ameliorate psychomotor&#xD;
      slowing in schizophrenia or major depression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Psychomotor slowing may occur in major psychiatric disorders, such as major depressive&#xD;
      disorders or schizophrenia spectrum disorders. It refers to slowing of fine motor skills,&#xD;
      motor planning and gross motor behavior. In major depression and schizophrenia, psychomotor&#xD;
      slowing is associated with alterations of premotor cortex, dorsolateral prefrontal cortex and&#xD;
      basal ganglia. This randomized, sham-controlled, prospective trial will test, whether 15&#xD;
      sessions of rTMS in 3 weeks may ameliorate psychomotor slowing in schizophrenia or major&#xD;
      depression.&#xD;
&#xD;
      Eligible participants will be randomized to one of four arms:&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2016</start_date>
  <completion_date type="Actual">July 15, 2019</completion_date>
  <primary_completion_date type="Actual">July 1, 2019</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>double-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Responders at Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>Number of participants with &gt;30% reduction from baseline in the Salpetriere Retardation Rating Scale, last observation carried forward method applied</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Salpetriere Retardation Rating Scale Total Score From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>observer based rating scale of the severity of psychomotor slowing, assessment blind to intervention Scores may range from 0 - 60, higher scores indicate worse outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Activity Level From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>actigraphically (wrist of the non-dominant arm) assessed motor activity during the wake periods of one day, given in counts/h</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Catatonia Severity From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>observer based rating of catatonia severity with the Bush Francis Catatonia Rating Scale, assessment blind to intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fingertapping Score From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>Fingertapping test with the dominant and nondominant index finger for 10 sec, video-taped and blind assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Coin Rotation From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>test of manual dexterity in both hands, rotation of a specified coin for 10 seconds, video-taped and blinded evaluation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Hand Gesture Performance From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>videotaped performance of hand gestures according to the Test of Upper Limb Apraxia (TULIA), blind evaluation and rating</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SANS Total Score From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>scale for the assessment of negative symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From HAMD Total Score From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>Hamilton Rating Scale for Depression, 21-item version, applies to depression patients, assessment blind to intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CAINS Total Score From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>the clinical assessment interview for negative symptoms, assessment blind to intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PANSS Total and Subscores From Baseline to Week 3</measure>
    <time_frame>week 3</time_frame>
    <description>the positive and negative syndrome scale, interview to assess severity of schizophrenia symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Psychomotor Retardation</condition>
  <condition>Psychomotor Slowing</condition>
  <condition>Schizophrenia and Related Disorders</condition>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>DLPFC facilitatory</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>repetitive transcranial magnetic stimulation (rTMS) of 15 Hz over left DLPFC&#xD;
usually effective in depression treatment, probably no specific effect on psychomotor slowing</description>
  </arm_group>
  <arm_group>
    <arm_group_label>preSMA/SMA inhibitory</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>repetitive transcranial magnetic stimulation (rTMS) of 1 Hz over preSMA/SMA&#xD;
should inhibit overactive premotor cortices</description>
  </arm_group>
  <arm_group>
    <arm_group_label>preSMA/SMA facilitatory</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>intermittend theta burst stimulation (iTBS) over preSMA/SMA&#xD;
should facilitate neural activity within premotor cortices</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sham TMS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>sham rTMS with a placebo coil over occipital cortex&#xD;
should have no effect at all (no transcranial magnetic stimulation, only sound)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>DLPFC facilitatory</intervention_name>
    <description>15 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC)(15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
    <arm_group_label>DLPFC facilitatory</arm_group_label>
    <other_name>rTMS facilitatory DLPFC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>SMA inhibitory</intervention_name>
    <description>1 Hz stimulation of preSMA/SMA (15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
    <arm_group_label>preSMA/SMA inhibitory</arm_group_label>
    <other_name>rTMS inhibitory SMA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>SMA facilitatory</intervention_name>
    <description>Three pulses of stimulation at 50 Hz of preSMA/SMA, repeated every 200 ms. 2 s trains are repeated every 10 s for a total of 190 s (600 pulses, 200 seconds). intensity 80% of individual active motor threshold; in total 9000 stimuli</description>
    <arm_group_label>preSMA/SMA facilitatory</arm_group_label>
    <other_name>iTBS facilitatory SMA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>sham TMS</intervention_name>
    <description>Determination of active motor threshold and subsequent stimulation with the placebo coil, with the same sounds but without effects. 15 sessions in three weeks, duration of 20 mins per session</description>
    <arm_group_label>sham TMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  suffering from major depressive disorder or schizophrenia spectrum disorder according&#xD;
             to DSM-5 criteria&#xD;
&#xD;
          -  right handedness&#xD;
&#xD;
          -  normal or corrected-to-normal vision and hearing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  epilepsy&#xD;
&#xD;
          -  history of severe head trauma&#xD;
&#xD;
          -  current abuse of drugs or alcohol; past addiction to drugs or alcohol&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  incompatibility to cerebral MRI&#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>Sebastian Walther, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Bern, University Hospital of Psychiatry</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital of Psychiatry, University of Bern</name>
      <address>
        <city>Bern</city>
        <zip>3008</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <results_first_submitted>May 26, 2020</results_first_submitted>
  <results_first_submitted_qc>May 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 12, 2021</results_first_posted>
  <last_update_submitted>May 11, 2021</last_update_submitted>
  <last_update_submitted_qc>May 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Bern</investigator_affiliation>
    <investigator_full_name>Sebastian Walther</investigator_full_name>
    <investigator_title>Prof. Dr., Head of the outpatient clinic, University Hospital of Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Mental Disorders</mesh_term>
    <mesh_term>Problem Behavior</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>May 20, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT03275766/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>DLPFC Facilitatory</title>
          <description>repetitive transcranial magnetic stimulation (rTMS) of 15 Hz over left DLPFC&#xD;
usually effective in depression treatment, probably no specific effect on psychomotor slowing&#xD;
DLPFC facilitatory: 15 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC)(15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
        </group>
        <group group_id="P2">
          <title>preSMA/SMA Inhibitory</title>
          <description>repetitive transcranial magnetic stimulation (rTMS) of 1 Hz over preSMA/SMA&#xD;
should inhibit overactive premotor cortices&#xD;
SMA inhibitory: 1 Hz stimulation of preSMA/SMA (15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
        </group>
        <group group_id="P3">
          <title>preSMA/SMA Facilitatory</title>
          <description>intermittend theta burst stimulation (iTBS) over preSMA/SMA&#xD;
should facilitate neural activity within premotor cortices&#xD;
SMA facilitatory: Three pulses of stimulation at 50 Hz of preSMA/SMA, repeated every 200 ms. 2 s trains are repeated every 10 s for a total of 190 s (600 pulses, 200 seconds). intensity 80% of individual active motor threshold; in total 9000 stimuli</description>
        </group>
        <group group_id="P4">
          <title>Sham TMS</title>
          <description>sham rTMS with a placebo coil over occipital cortex&#xD;
should have no effect at all (no transcranial magnetic stimulation, only sound)&#xD;
sham TMS: Determination of active motor threshold and subsequent stimulation with the placebo coil, with the same sounds but without effects. 15 sessions in three weeks, duration of 20 mins per session</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="11"/>
                <participants group_id="P4" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Intervention</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>one subject randomized withdrew consent before the baseline assessments</population>
      <group_list>
        <group group_id="B1">
          <title>DLPFC Facilitatory</title>
          <description>repetitive transcranial magnetic stimulation (rTMS) of 15 Hz over left DLPFC&#xD;
usually effective in depression treatment, probably no specific effect on psychomotor slowing&#xD;
DLPFC facilitatory: 15 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC)(15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
        </group>
        <group group_id="B2">
          <title>preSMA/SMA Inhibitory</title>
          <description>repetitive transcranial magnetic stimulation (rTMS) of 1 Hz over preSMA/SMA&#xD;
should inhibit overactive premotor cortices&#xD;
SMA inhibitory: 1 Hz stimulation of preSMA/SMA (15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
        </group>
        <group group_id="B3">
          <title>preSMA/SMA Facilitatory</title>
          <description>intermittend theta burst stimulation (iTBS) over preSMA/SMA&#xD;
should facilitate neural activity within premotor cortices&#xD;
SMA facilitatory: Three pulses of stimulation at 50 Hz of preSMA/SMA, repeated every 200 ms. 2 s trains are repeated every 10 s for a total of 190 s (600 pulses, 200 seconds). intensity 80% of individual active motor threshold; in total 9000 stimuli</description>
        </group>
        <group group_id="B4">
          <title>Sham TMS</title>
          <description>sham rTMS with a placebo coil over occipital cortex&#xD;
should have no effect at all (no transcranial magnetic stimulation, only sound)&#xD;
sham TMS: Determination of active motor threshold and subsequent stimulation with the placebo coil, with the same sounds but without effects. 15 sessions in three weeks, duration of 20 mins per session</description>
        </group>
        <group group_id="B5">
          <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="12"/>
            <count group_id="B2" value="11"/>
            <count group_id="B3" value="11"/>
            <count group_id="B4" value="10"/>
            <count group_id="B5" value="44"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="11"/>
                    <count group_id="B3" value="11"/>
                    <count group_id="B4" value="10"/>
                    <count group_id="B5" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" 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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="11"/>
                    <count group_id="B3" value="11"/>
                    <count group_id="B4" value="10"/>
                    <count group_id="B5" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.3" spread="15.2"/>
                    <measurement group_id="B2" value="38.0" spread="15.6"/>
                    <measurement group_id="B3" value="34.2" spread="14.0"/>
                    <measurement group_id="B4" value="41.2" spread="15.3"/>
                    <measurement group_id="B5" value="39.5" spread="15.0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="11"/>
                    <count group_id="B3" value="11"/>
                    <count group_id="B4" value="10"/>
                    <count group_id="B5" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                    <count group_id="B4" value="0"/>
                    <count group_id="B5" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B5" 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>Switzerland</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="11"/>
                    <count group_id="B3" value="11"/>
                    <count group_id="B4" value="10"/>
                    <count group_id="B5" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="10"/>
                    <measurement group_id="B5" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diagnosis</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>major depression</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="11"/>
                    <count group_id="B3" value="11"/>
                    <count group_id="B4" value="10"/>
                    <count group_id="B5" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>schizophrenia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="12"/>
                    <count group_id="B2" value="11"/>
                    <count group_id="B3" value="11"/>
                    <count group_id="B4" value="10"/>
                    <count group_id="B5" value="44"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Responders at Week 3</title>
        <description>Number of participants with &gt;30% reduction from baseline in the Salpetriere Retardation Rating Scale, last observation carried forward method applied</description>
        <time_frame>week 3</time_frame>
        <group_list>
          <group group_id="O1">
            <title>DLPFC Facilitatory</title>
            <description>repetitive transcranial magnetic stimulation (rTMS) of 15 Hz over left DLPFC&#xD;
usually effective in depression treatment, probably no specific effect on psychomotor slowing&#xD;
DLPFC facilitatory: 15 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC)(15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
          </group>
          <group group_id="O2">
            <title>preSMA/SMA Inhibitory</title>
            <description>repetitive transcranial magnetic stimulation (rTMS) of 1 Hz over preSMA/SMA&#xD;
should inhibit overactive premotor cortices&#xD;
SMA inhibitory: 1 Hz stimulation of preSMA/SMA (15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
          </group>
          <group group_id="O3">
            <title>preSMA/SMA Facilitatory</title>
            <description>intermittend theta burst stimulation (iTBS) over preSMA/SMA&#xD;
should facilitate neural activity within premotor cortices&#xD;
SMA facilitatory: Three pulses of stimulation at 50 Hz of preSMA/SMA, repeated every 200 ms. 2 s trains are repeated every 10 s for a total of 190 s (600 pulses, 200 seconds). intensity 80% of individual active motor threshold; in total 9000 stimuli</description>
          </group>
          <group group_id="O4">
            <title>Sham TMS</title>
            <description>sham rTMS with a placebo coil over occipital cortex&#xD;
should have no effect at all (no transcranial magnetic stimulation, only sound)&#xD;
sham TMS: Determination of active motor threshold and subsequent stimulation with the placebo coil, with the same sounds but without effects. 15 sessions in three weeks, duration of 20 mins per session</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Responders at Week 3</title>
          <description>Number of participants with &gt;30% reduction from baseline in the Salpetriere Retardation Rating Scale, last observation carried forward method applied</description>
          <units>responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="11"/>
                <count group_id="O3" value="11"/>
                <count group_id="O4" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Salpetriere Retardation Rating Scale Total Score From Baseline to Week 3</title>
        <description>observer based rating scale of the severity of psychomotor slowing, assessment blind to intervention Scores may range from 0 - 60, higher scores indicate worse outcome</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Activity Level From Baseline to Week 3</title>
        <description>actigraphically (wrist of the non-dominant arm) assessed motor activity during the wake periods of one day, given in counts/h</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Catatonia Severity From Baseline to Week 3</title>
        <description>observer based rating of catatonia severity with the Bush Francis Catatonia Rating Scale, assessment blind to intervention</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Fingertapping Score From Baseline to Week 3</title>
        <description>Fingertapping test with the dominant and nondominant index finger for 10 sec, video-taped and blind assessment</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Coin Rotation From Baseline to Week 3</title>
        <description>test of manual dexterity in both hands, rotation of a specified coin for 10 seconds, video-taped and blinded evaluation</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Hand Gesture Performance From Baseline to Week 3</title>
        <description>videotaped performance of hand gestures according to the Test of Upper Limb Apraxia (TULIA), blind evaluation and rating</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in SANS Total Score From Baseline to Week 3</title>
        <description>scale for the assessment of negative symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From HAMD Total Score From Baseline to Week 3</title>
        <description>Hamilton Rating Scale for Depression, 21-item version, applies to depression patients, assessment blind to intervention</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in CAINS Total Score From Baseline to Week 3</title>
        <description>the clinical assessment interview for negative symptoms, assessment blind to intervention</description>
        <time_frame>week 3</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in PANSS Total and Subscores From Baseline to Week 3</title>
        <description>the positive and negative syndrome scale, interview to assess severity of schizophrenia symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention</description>
        <time_frame>week 3</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Data was collected during and after the daily rTMS sessions, inquiry covered the total three weeks of the trial</time_frame>
      <desc>inquiry with open questions</desc>
      <group_list>
        <group group_id="E1">
          <title>DLPFC Facilitatory</title>
          <description>repetitive transcranial magnetic stimulation (rTMS) of 15 Hz over left DLPFC&#xD;
usually effective in depression treatment, probably no specific effect on psychomotor slowing&#xD;
DLPFC facilitatory: 15 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC)(15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
        </group>
        <group group_id="E2">
          <title>preSMA/SMA Inhibitory</title>
          <description>repetitive transcranial magnetic stimulation (rTMS) of 1 Hz over preSMA/SMA&#xD;
should inhibit overactive premotor cortices&#xD;
SMA inhibitory: 1 Hz stimulation of preSMA/SMA (15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli</description>
        </group>
        <group group_id="E3">
          <title>preSMA/SMA Facilitatory</title>
          <description>intermittend theta burst stimulation (iTBS) over preSMA/SMA&#xD;
should facilitate neural activity within premotor cortices&#xD;
SMA facilitatory: Three pulses of stimulation at 50 Hz of preSMA/SMA, repeated every 200 ms. 2 s trains are repeated every 10 s for a total of 190 s (600 pulses, 200 seconds). intensity 80% of individual active motor threshold; in total 9000 stimuli</description>
        </group>
        <group group_id="E4">
          <title>Sham TMS</title>
          <description>sham rTMS with a placebo coil over occipital cortex&#xD;
should have no effect at all (no transcranial magnetic stimulation, only sound)&#xD;
sham TMS: Determination of active motor threshold and subsequent stimulation with the placebo coil, with the same sounds but without effects. 15 sessions in three weeks, duration of 20 mins per session</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Deterioration of psychiatric disorder</sub_title>
                <description>one patient experienced a deterioration of the underlying psychiatric disorder (major depression), which required short term hospitalization. The intervention was stopped. The problem resolved and the patient was discharged from the hospital.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="10"/>
              </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="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>mild nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>altered visual perception</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </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. Sebastian Walther</name_or_title>
      <organization>University of Bern, University Hospital of Psychiatry, Bern</organization>
      <phone>+41 632 8979</phone>
      <email>sebastian.walther@upd.unibe.ch</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/NCT03275766
org study id: SNCTP610
nct id: NCT03275766
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Psychomotor slowing may occur in major psychiatric disorders, such as major depressive
      disorders or schizophrenia spectrum disorders. It refers to slowing of fine motor skills,
      motor planning and gross motor behavior. In major depression and schizophrenia, psychomotor
      slowing is associated with alterations of premotor cortex, dorsolateral prefrontal cortex and
      basal ganglia. This randomized, sham-controlled, prospective trial will test, whether 15
      sessions of repetitive transcranial magnetic stimulation (rTMS) may ameliorate psychomotor
      slowing in schizophrenia or major depression.
Psychomotor slowing may occur in major psychiatric disorders, such as major depressive
      disorders or schizophrenia spectrum disorders. It refers to slowing of fine motor skills,
      motor planning and gross motor behavior. In major depression and schizophrenia, psychomotor
      slowing is associated with alterations of premotor cortex, dorsolateral prefrontal cortex and
      basal ganglia. This randomized, sham-controlled, prospective trial will test, whether 15
      sessions of rTMS in 3 weeks may ameliorate psychomotor slowing in schizophrenia or major
      depression.

      Eligible participants will be randomized to one of four arms:
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Outcomes Assessor)
masking description: double-blind
measure: Number of Responders at Week 3
time frame: week 3
description: Number of participants with >30% reduction from baseline in the Salpetriere Retardation Rating Scale, last observation carried forward method applied
measure: Change in Salpetriere Retardation Rating Scale Total Score From Baseline to Week 3
time frame: week 3
description: observer based rating scale of the severity of psychomotor slowing, assessment blind to intervention Scores may range from 0 - 60, higher scores indicate worse outcome
measure: Change in Activity Level From Baseline to Week 3
time frame: week 3
description: actigraphically (wrist of the non-dominant arm) assessed motor activity during the wake periods of one day, given in counts/h
measure: Change in Catatonia Severity From Baseline to Week 3
time frame: week 3
description: observer based rating of catatonia severity with the Bush Francis Catatonia Rating Scale, assessment blind to intervention
measure: Change in Fingertapping Score From Baseline to Week 3
time frame: week 3
description: Fingertapping test with the dominant and nondominant index finger for 10 sec, video-taped and blind assessment
measure: Change in Coin Rotation From Baseline to Week 3
time frame: week 3
description: test of manual dexterity in both hands, rotation of a specified coin for 10 seconds, video-taped and blinded evaluation
measure: Change in Hand Gesture Performance From Baseline to Week 3
time frame: week 3
description: videotaped performance of hand gestures according to the Test of Upper Limb Apraxia (TULIA), blind evaluation and rating
measure: Change in SANS Total Score From Baseline to Week 3
time frame: week 3
description: scale for the assessment of negative symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention
measure: Change From HAMD Total Score From Baseline to Week 3
time frame: week 3
description: Hamilton Rating Scale for Depression, 21-item version, applies to depression patients, assessment blind to intervention
measure: Change in CAINS Total Score From Baseline to Week 3
time frame: week 3
description: the clinical assessment interview for negative symptoms, assessment blind to intervention
measure: Change in PANSS Total and Subscores From Baseline to Week 3
time frame: week 3
description: the positive and negative syndrome scale, interview to assess severity of schizophrenia symptoms, applies to schizophrenia spectrum disorder patients, assessment blind to intervention
arm group label: DLPFC facilitatory
arm group type: Active Comparator
description: repetitive transcranial magnetic stimulation (rTMS) of 15 Hz over left DLPFC
usually effective in depression treatment, probably no specific effect on psychomotor slowing
arm group label: preSMA/SMA inhibitory
arm group type: Experimental
description: repetitive transcranial magnetic stimulation (rTMS) of 1 Hz over preSMA/SMA
should inhibit overactive premotor cortices
arm group label: preSMA/SMA facilitatory
arm group type: Experimental
description: intermittend theta burst stimulation (iTBS) over preSMA/SMA
should facilitate neural activity within premotor cortices
arm group label: sham TMS
arm group type: Sham Comparator
description: sham rTMS with a placebo coil over occipital cortex
should have no effect at all (no transcranial magnetic stimulation, only sound)
intervention type: Other
intervention name: DLPFC facilitatory
description: 15 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC)(15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli
arm group label: DLPFC facilitatory
other name: rTMS facilitatory DLPFC
intervention type: Other
intervention name: SMA inhibitory
description: 1 Hz stimulation of preSMA/SMA (15 sessions/3weeks, 1500 stimuli per session, stimulation intensity 100% of the individual active motor threshold; in total 22500 stimuli
arm group label: preSMA/SMA inhibitory
other name: rTMS inhibitory SMA
intervention type: Other
intervention name: SMA facilitatory
description: Three pulses of stimulation at 50 Hz of preSMA/SMA, repeated every 200 ms. 2 s trains are repeated every 10 s for a total of 190 s (600 pulses, 200 seconds). intensity 80% of individual active motor threshold; in total 9000 stimuli
arm group label: preSMA/SMA facilitatory
other name: iTBS facilitatory SMA
intervention type: Other
intervention name: sham TMS
description: Determination of active motor threshold and subsequent stimulation with the placebo coil, with the same sounds but without effects. 15 sessions in three weeks, duration of 20 mins per session
arm group label: sham TMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Sebastian Walther, MD
role: Principal Investigator
affiliation: University of Bern, University Hospital of Psychiatry
facility: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: University of Bern
investigator full name: Sebastian Walther
investigator title: Prof. Dr., Head of the outpatient clinic, University Hospital of Psychiatry
mesh term: Schizophrenia
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Mental Disorders
mesh term: Problem Behavior
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 