<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/NCT03288714</url>
  </required_header>
  <id_info>
    <org_study_id>NND-3002</org_study_id>
    <nct_id>NCT03288714</nct_id>
  </id_info>
  <brief_title>Adaptive Design Study of NEST sTMS in Subjects With Major Depressive Disorder</brief_title>
  <official_title>A Prospective, Multicenter, Double-Blind, Sham-Controlled Adaptive Design Study to Confirm the Safety and Efficacy of NEST sTMS in Subjects With Major Depressive Disorder Who Have Not Responded to at Least One Antidepressant Medication in the Current Episode</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wave Neuroscience</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Wave Neuroscience</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a double-blind, sham controlled, multi-center study to confirm the safety and&#xD;
      efficacy of synchronized transcranial magnetic stimulation (sTMS) for the treatment of&#xD;
      patients currently experiencing an episode of depression who have failed to respond to at&#xD;
      least one (1) antidepressant medication. Patients will be randomly assigned to either active&#xD;
      or sham therapy and will undergo daily treatments for a period of time. Following completion&#xD;
      of blinded treatments, patients may be eligible for a course of open label treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prospective, randomized, double-blind, sham-controlled, parallel group adaptive design study&#xD;
      to confirm the safety and efficacy of sTMS in subject with Major Depressive Disorder (MDD)&#xD;
      who have not responded to at least one antidepressant medication in the current episode. MDD&#xD;
      was diagnosed according to DSM-IV criteria rendered by structured interview using the Mini&#xD;
      International Neuropsychiatric Interview (MINI).&#xD;
&#xD;
      Subjects must have discontinued any antidepressant medication a minimum of 1 week prior to&#xD;
      initiation of treatment with the active sTMS or sham device. Following wash-out of the&#xD;
      antidepressant medication, an additional evaluation was performed to determine whether the&#xD;
      protocol eligibility criteria were met before randomization and treatment.&#xD;
&#xD;
      Randomized subjects were treated 5 days per week for 6 weeks. Subjects who completed 6 weeks&#xD;
      of double-blind treatment may have been eligible to receive up to 6 weeks of open-label&#xD;
      treatment as clinically indicated during the follow-up phase of the study.&#xD;
&#xD;
      Follow-up evaluation visits were conducted during those six weeks, with frequency of the&#xD;
      visits determined by the treatment choice during that time frame (open label subjects had&#xD;
      weekly evaluation visits for 6 weeks).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 27, 2017</start_date>
  <completion_date type="Actual">June 1, 2019</completion_date>
  <primary_completion_date type="Actual">March 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>
    <intervention_model_description>Sham Controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population</measure>
    <time_frame>Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6</time_frame>
    <description>Number of participants at the end of each treatment week who saw a reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment</measure>
    <time_frame>Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6</time_frame>
    <description>Change from the baseline in HAMD-17 total score from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population</measure>
    <time_frame>Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6</time_frame>
    <description>Change from the baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The MADRS scale ranges between 0-54, with higher numbers indicating more severe symptoms. 0-6 is generally accepted to be within the normal range (or in remission), 7-19 represents mild depression, while a score of 20 or higher indicates moderate to severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz</measure>
    <time_frame>Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6</time_frame>
    <description>Measure of change in mean (SD) of HAMD-17 scores from baseline to end of treatment in per-protocol patients with an Individual alpha frequency (IAF) of greater than 9.8Hz.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments</measure>
    <time_frame>Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12</time_frame>
    <description>Change in HAMD-17 total score during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population</measure>
    <time_frame>Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12</time_frame>
    <description>Number of participants seeing reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">121</enrollment>
  <condition>Depressive Disorder</condition>
  <condition>Depression</condition>
  <condition>Depressive Disorder, Major</condition>
  <condition>Depressive Episode</condition>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Active sTMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Synchronized Transcranial Magnetic Stimulation (sTMS)</intervention_name>
    <description>sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
    <arm_group_label>Active sTMS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Stimulation</intervention_name>
    <description>Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</description>
    <arm_group_label>Sham Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Current episode of Major Depressive Disorder&#xD;
&#xD;
          -  Inadequate response to at least one antidepressant medication in the current episode&#xD;
             (Treatment Resistant Depression)&#xD;
&#xD;
          -  Investigator able to identify IAF using EEG&#xD;
&#xD;
          -  Willingness and ability to adhere to treatment schedule (5 treatments per week for six&#xD;
             weeks)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to unwilling to give informed consent&#xD;
&#xD;
          -  Diagnosed with excluded conditions or treatment histories&#xD;
&#xD;
          -  Currently hospitalized due to severity of depression symptoms&#xD;
&#xD;
          -  Use of prohibited medications (as defined by protocol) within specified time frame of&#xD;
             randomization&#xD;
&#xD;
          -  Use of certain cardiac devices&#xD;
&#xD;
          -  Use of certain intracranial devices&#xD;
&#xD;
          -  Currently pregnant or unwilling to practice acceptable means of birth control, and&#xD;
             women who are breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew Leuchter, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kadima Neuropsychiatry Institute</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Westwood - Semel Institute for Neuroscience and Human Behavior</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90024</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30329</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheppard Pratt Health System</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University/Barnes Jewish Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laureate Institute for Brain Research</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Butler Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02906</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Health Consultants</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>September 18, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 20, 2017</study_first_posted>
  <results_first_submitted>July 12, 2021</results_first_submitted>
  <results_first_submitted_qc>August 9, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">September 5, 2021</results_first_posted>
  <last_update_submitted>August 9, 2021</last_update_submitted>
  <last_update_submitted_qc>August 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Transcranial Magnetic Stimulation</keyword>
  <keyword>TMS</keyword>
  <keyword>sTMS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 7, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03288714/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 26, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/14/NCT03288714/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited through local referral networks, as well as online study descriptions, printed flyers, and radio advertisements approved by Institutional Review Boards (IRB). Recruitment was accomplished through initial interview and in-person screening assessments determining eligibility.</recruitment_details>
      <pre_assignment_details>Following enrollment and completion of informed consent, participants were randomized to a treatment arm. Participants were instructed to discontinue any current antidepressant medication a minimum of 1 week prior to initiation of treatment, and confirmation of eligibility was completed after the wash-out.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Active sTMS</title>
          <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
        </group>
        <group group_id="P2">
          <title>Sham Stimulation</title>
          <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="59"/>
                <participants group_id="P2" count="62"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="49"/>
                <participants group_id="P2" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance with study schedule</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Clinical Worsening</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline demographics taken from the per-protocol (PP) population; the PP group includes all participants who signed an informed consent, met study criteria, were randomized to a treatment arm, received at least 80% (24/30) of scheduled treatments within 60 days and completed the required treatment and post-baseline assessments in the double-blind phase</population>
      <group_list>
        <group group_id="B1">
          <title>Active sTMS</title>
          <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
        </group>
        <group group_id="B2">
          <title>Sham Stimulation</title>
          <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</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="46"/>
            <count group_id="B2" value="57"/>
            <count group_id="B3" value="103"/>
          </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="45" spread="11.3"/>
                    <measurement group_id="B2" value="46.1" spread="13.0"/>
                    <measurement group_id="B3" value="45.6" spread="12.15"/>
                  </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="32"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian/Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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="46"/>
                    <measurement group_id="B2" value="57"/>
                    <measurement group_id="B3" value="103"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Education Level</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Some high school or less</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>High school diploma</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vocational school</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Some college</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>College degree</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Professional or graduate degree</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population</title>
        <description>Number of participants at the end of each treatment week who saw a reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
        <time_frame>Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6</time_frame>
        <population>121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.</population>
        <group_list>
          <group group_id="O1">
            <title>Active sTMS</title>
            <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population</title>
          <description>Number of participants at the end of each treatment week who saw a reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
          <population>121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="12"/>
                  </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>
            <groups_desc>Null hypothesis is that the active sTMS treatment group does not differ from the sham group with respect to the proportion of patients with clinical response at Week 6.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.814</p_value>
            <method>Fisher Exact</method>
            <method_desc>The proportion of patients is compared across treatment groups using Fisher's Exact.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment</title>
        <description>Change from the baseline in HAMD-17 total score from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
        <time_frame>Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6</time_frame>
        <population>121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.</population>
        <group_list>
          <group group_id="O1">
            <title>Active sTMS</title>
            <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment</title>
          <description>Change from the baseline in HAMD-17 total score from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
          <population>121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.</population>
          <units>score on HAMD-17 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="46"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.96" spread="2.81"/>
                    <measurement group_id="O2" value="22.04" spread="4.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.30" spread="5.14"/>
                    <measurement group_id="O2" value="-4.33" spread="3.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.63" spread="4.99"/>
                    <measurement group_id="O2" value="-6.65" spread="4.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.76" spread="5.48"/>
                    <measurement group_id="O2" value="-7.74" spread="5.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.61" spread="5.63"/>
                    <measurement group_id="O2" value="-7.93" spread="6.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.93" spread="5.81"/>
                    <measurement group_id="O2" value="-7.95" spread="6.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.57" spread="5.50"/>
                    <measurement group_id="O2" value="-6.81" spread="6.48"/>
                  </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>
            <groups_desc>Null hypothesis is that the active sTMS treatment group does not differ from the sham group with respect to the proportion of patients with clinical response at Week 6.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.872</p_value>
            <method>ANCOVA</method>
            <method_desc>P-value is from analysis of covariance adjusting for baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population</title>
        <description>Change from the baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The MADRS scale ranges between 0-54, with higher numbers indicating more severe symptoms. 0-6 is generally accepted to be within the normal range (or in remission), 7-19 represents mild depression, while a score of 20 or higher indicates moderate to severe depression.</description>
        <time_frame>Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6</time_frame>
        <population>121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.</population>
        <group_list>
          <group group_id="O1">
            <title>Active sTMS</title>
            <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population</title>
          <description>Change from the baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6, compared between the active treatment and sham-controlled groups.&#xD;
The MADRS scale ranges between 0-54, with higher numbers indicating more severe symptoms. 0-6 is generally accepted to be within the normal range (or in remission), 7-19 represents mild depression, while a score of 20 or higher indicates moderate to severe depression.</description>
          <population>121 subjects were randomized into the study. Of those, 13 subjects dropped out of the study for various reasons and 5 were excluded from per-protocol analysis, as they failed to meet protocol requirements. Per-protocol analysis was performed on the remaining 103 subjects.</population>
          <units>score on MADRS 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="46"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.89" spread="4.57"/>
                    <measurement group_id="O2" value="30.72" spread="5.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.02" spread="8.25"/>
                    <measurement group_id="O2" value="-5.39" spread="5.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.91" spread="7.46"/>
                    <measurement group_id="O2" value="-8.63" spread="8.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.76" spread="8.57"/>
                    <measurement group_id="O2" value="-9.47" spread="9.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.89" spread="9.81"/>
                    <measurement group_id="O2" value="-10.12" spread="9.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.11" spread="8.64"/>
                    <measurement group_id="O2" value="-10.81" spread="8.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.52" spread="8.75"/>
                    <measurement group_id="O2" value="-9.77" spread="9.56"/>
                  </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>
            <groups_desc>The null hypothesis is that the active sTMS treatment group does not differ</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.641</p_value>
            <method>ANCOVA</method>
            <method_desc>P-value is from analysis of covariance adjusting for baseline.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz</title>
        <description>Measure of change in mean (SD) of HAMD-17 scores from baseline to end of treatment in per-protocol patients with an Individual alpha frequency (IAF) of greater than 9.8Hz.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
        <time_frame>Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6</time_frame>
        <population>Subjects in the per-protocol group with IAF greater than 9.8 Hz.</population>
        <group_list>
          <group group_id="O1">
            <title>Active sTMS (IAF &gt; 9.8Hz)</title>
            <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF), subgroup of those participants were found to be greater than 9.8Hz</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation (IAF&gt;9.8Hz)</title>
            <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain. All patients analyzed and compared with other belonging to same subgroup of those with IAF greater than 9.8Hz.</description>
          </group>
        </group_list>
        <measure>
          <title>Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz</title>
          <description>Measure of change in mean (SD) of HAMD-17 scores from baseline to end of treatment in per-protocol patients with an Individual alpha frequency (IAF) of greater than 9.8Hz.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
          <population>Subjects in the per-protocol group with IAF greater than 9.8 Hz.</population>
          <units>score on HAMD-17 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="19"/>
                <count group_id="O2" value="33"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.68" spread="2.65"/>
                    <measurement group_id="O2" value="21.91" spread="3.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.05" spread="6.11"/>
                    <measurement group_id="O2" value="-4.12" spread="3.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.32" spread="5.75"/>
                    <measurement group_id="O2" value="-6.15" spread="4.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.11" spread="5.37"/>
                    <measurement group_id="O2" value="-7.70" spread="4.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.89" spread="4.74"/>
                    <measurement group_id="O2" value="-6.97" spread="4.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.53" spread="6.01"/>
                    <measurement group_id="O2" value="-6.97" spread="6.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.47" spread="5.11"/>
                    <measurement group_id="O2" value="-5.18" spread="5.72"/>
                  </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>.032</p_value>
            <p_value_desc>Alpha level: .05</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>P-value is from analysis of covariance adjusting for baseline</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments</title>
        <description>Change in HAMD-17 total score during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
        <time_frame>Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12</time_frame>
        <population>Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Active sTMS</title>
            <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments</title>
          <description>Change in HAMD-17 total score during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
          <population>Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis.</population>
          <units>score on HAMD-17 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="38"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>sTMS Active Treatment Week 6/Sham Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.50" spread="4.69"/>
                    <measurement group_id="O2" value="16.76" spread="5.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Open-Label Week 1 (Active Week 7/Sham Week 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.82" spread="5.34"/>
                    <measurement group_id="O2" value="-3.98" spread="5.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Open-Label Week 2 (Active Week 8/Sham Week 2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.36" spread="5.96"/>
                    <measurement group_id="O2" value="-3.69" spread="5.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Open-Label Week 3 (Active Week 9/Sham Week 3)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.09" spread="6.58"/>
                    <measurement group_id="O2" value="-4.29" spread="5.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Open-Label Week 4 (Active Week 10/Sham Week 4)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.68" spread="7.34"/>
                    <measurement group_id="O2" value="-4.51" spread="5.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Open-Label Week 5 (Active Week 11/Sham Week 5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.34" spread="6.54"/>
                    <measurement group_id="O2" value="-5.47" spread="5.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change from Baseline to Open-Label Week 6 (Active Week 12/Sham Week 6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.72" spread="6.97"/>
                    <measurement group_id="O2" value="-6.42" spread="5.01"/>
                  </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>.015</p_value>
            <p_value_desc>Alpha level: .05</p_value_desc>
            <method>ANCOVA</method>
            <method_desc>P-value is from analysis of covariance adjusting for baseline</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population</title>
        <description>Number of participants seeing reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
        <time_frame>Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12</time_frame>
        <population>Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Active sTMS</title>
            <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
          </group>
          <group group_id="O2">
            <title>Sham Stimulation</title>
            <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population</title>
          <description>Number of participants seeing reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups.&#xD;
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.</description>
          <population>Of the 103 subjects in the original per-protocol group, 83 continued to open-label treatment for analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Open Label Week 1 (Active Week 7/Sham Week 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Open Label Week 2 (Active Week 8/Sham Week 2)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Open Label Week 3 (Active Week 9/Sham Week 3)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Open Label Week 4 (Active Week 10/Sham Week 4)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Open Label Week 5 (Active Week 11/Sham Week 5)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Open Label Week 6 (Active Week 12/Sham Week 6)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="12"/>
                  </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>.028</p_value>
            <p_value_desc>Alpha level: .05</p_value_desc>
            <method>Fisher Exact</method>
            <method_desc>The proportion of patients is compared across treatment groups using Fisher's Exact.</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All subjects screened at Screening, Baseline, and each Evaluation Visit (End of Weeks 1, 2, 3, 4, 5, 6; if continuing open-label 7, 8, 9, 10, 11, 12)</time_frame>
      <desc>All adverse events were entered by study personnel verbatim based on patient reports.&#xD;
Any adverse event occurring before randomization occurred was not included in the final report.</desc>
      <group_list>
        <group group_id="E1">
          <title>Active sTMS</title>
          <description>Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.&#xD;
Synchronized Transcranial Magnetic Stimulation (sTMS): sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).</description>
        </group>
        <group group_id="E2">
          <title>Sham Stimulation</title>
          <description>Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.&#xD;
Sham Stimulation: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.</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="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic Reaction (peanut allergy)</sub_title>
                <description>Subject in Open-label portion of study had anaphylactic reaction to peanuts and was admitted to hospital for treatment. Subject continued treatment normally.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hospitalization (Suicidal Ideation)</sub_title>
                <description>Patient exhibited increased depressive symptoms and suicidal ideation and was subsequently admitted to the hospital for suicidal ideation.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</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="35" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Visual Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>GI Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Cramping</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Oral Herpes</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Muscle Twitching</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </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" subjects_affected="7" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Jaw Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Musculoskeletal Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Shoulder Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="62"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory Infection</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Application Site Discomfort</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="59"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="62"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <limitations_and_caveats>Sham device used exaggerated vibration at the IAF which may have provided active treatment in the form of trigeminal nerve stimulation&#xD;
Short wash-out period may have negatively impacted results.&#xD;
Short treatment duration may limit efficacy</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Meagan Kovacs, Clinical and Regulatory Affairs Manager</name_or_title>
      <organization>Wave Neuroscience</organization>
      <phone>9492292869</phone>
      <email>meagan@waveneuro.com</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/NCT03288714
org study id: NND-3002
nct id: NCT03288714
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: No
This is a double-blind, sham controlled, multi-center study to confirm the safety and
      efficacy of synchronized transcranial magnetic stimulation (sTMS) for the treatment of
      patients currently experiencing an episode of depression who have failed to respond to at
      least one (1) antidepressant medication. Patients will be randomly assigned to either active
      or sham therapy and will undergo daily treatments for a period of time. Following completion
      of blinded treatments, patients may be eligible for a course of open label treatments.
Prospective, randomized, double-blind, sham-controlled, parallel group adaptive design study
      to confirm the safety and efficacy of sTMS in subject with Major Depressive Disorder (MDD)
      who have not responded to at least one antidepressant medication in the current episode. MDD
      was diagnosed according to DSM-IV criteria rendered by structured interview using the Mini
      International Neuropsychiatric Interview (MINI).

      Subjects must have discontinued any antidepressant medication a minimum of 1 week prior to
      initiation of treatment with the active sTMS or sham device. Following wash-out of the
      antidepressant medication, an additional evaluation was performed to determine whether the
      protocol eligibility criteria were met before randomization and treatment.

      Randomized subjects were treated 5 days per week for 6 weeks. Subjects who completed 6 weeks
      of double-blind treatment may have been eligible to receive up to 6 weeks of open-label
      treatment as clinically indicated during the follow-up phase of the study.

      Follow-up evaluation visits were conducted during those six weeks, with frequency of the
      visits determined by the treatment choice during that time frame (open label subjects had
      weekly evaluation visits for 6 weeks).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Sham Controlled
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-Blind
measure: Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Per-Protocol Population
time frame: Baseline (Day 0) to End of Weeks 1, 2, 3, 4, 5, 6
description: Number of participants at the end of each treatment week who saw a reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores from baseline to week 6, compared between the active treatment and sham-controlled groups.
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
measure: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment
time frame: Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
description: Change from the baseline in HAMD-17 total score from baseline to week 6, compared between the active treatment and sham-controlled groups.
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
measure: Mean Change (SD) in MADRS Scores From Baseline to End of Treatment in the Per-Protocol Population
time frame: Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
description: Change from the baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6, compared between the active treatment and sham-controlled groups.
The MADRS scale ranges between 0-54, with higher numbers indicating more severe symptoms. 0-6 is generally accepted to be within the normal range (or in remission), 7-19 represents mild depression, while a score of 20 or higher indicates moderate to severe depression.
measure: Responder Analysis: Mean Change (SD) in HAMD-17 Scores From Baseline to End of Treatment in Per-Protocol Patients With Individual Alpha Frequency Greater Than 9.8 Hz
time frame: Baseline (Day 0) and End of Weeks 1, 2, 3, 4, 5, 6
description: Measure of change in mean (SD) of HAMD-17 scores from baseline to end of treatment in per-protocol patients with an Individual alpha frequency (IAF) of greater than 9.8Hz.
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
measure: Mean Change (SD) in HAMD-17 Scores From Baseline to Week 6 of Open-Label Treatments
time frame: Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12
description: Change in HAMD-17 total score during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups.
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
measure: Incidence of Clinical Response (Reduction of At Least 50% in Baseline HAMD-17 Score) in Open-Label Per-Protocol Population
time frame: Baseline (sTMS Week 6/Sham Baseline) and End of Weeks 7, 8, 9, 10, 11, 12
description: Number of participants seeing reduction of at least 50% in baseline Hamilton Depression Rating Scale (HAMD-17) scores during 6 weeks of open-label treatment, compared between the active treatment and sham-controlled groups.
The Hamilton Depression Rating Scale (HAMD-17) system asks 17 questions to rank subject on a scale ranges between 0-52, with higher numbers indicating more severe symptoms. 0-7 is generally accepted to be within the normal range (or in remission), while a score of 20 or higher indicates moderate to severe depression.
arm group label: Active sTMS
arm group type: Experimental
description: Synchronized Transcranial Magnetic Stimulation (sTMS) treatments to be administered using an active device 5 times per week for six treatment weeks.
arm group label: Sham Stimulation
arm group type: Sham Comparator
description: Sham treatments to be administered using a sham device 5 times per week for six treatment weeks.
intervention type: Device
intervention name: Synchronized Transcranial Magnetic Stimulation (sTMS)
description: sTMS delivers brain stimulation via a continuous magnetic field created by the device and set to the individual patient's intrinsic alpha frequency (IAF).
arm group label: Active sTMS
intervention type: Device
intervention name: Sham Stimulation
description: Sham stimulation is designed to look, sound and feel like the investigational device, but does not deliver magnetic stimulation to the brain.
arm group label: Sham Stimulation
criteria: 
gender: All
minimum age: 22 Years
maximum age: 65 Years
healthy volunteers: No
last name: Andrew Leuchter, MD
role: Principal Investigator
affiliation: University of California, Los Angeles
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country: United States
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
sharing ipd: No
provided document: 
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participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Sham device used exaggerated vibration at the IAF which may have provided active treatment in the form of trigeminal nerve stimulation
Short wash-out period may have negatively impacted results.
Short treatment duration may limit efficacy
point of contact: 