<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/NCT02998580</url>
  </required_header>
  <id_info>
    <org_study_id>076-2016</org_study_id>
    <nct_id>NCT02998580</nct_id>
  </id_info>
  <brief_title>Conventional Bilateral rTMS vs. Bilateral Theta Burst Stimulation for Late-Life Depression</brief_title>
  <official_title>Conventional Bilateral rTMS vs. Bilateral Theta Burst Stimulation for Late-Life Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial will compare conventional sequential bilateral rTMS to a bilateral theta burst&#xD;
      stimulation protocol. The right and left dorsolateral prefrontal cortices will be the site of&#xD;
      stimulation in both treatment conditions. The site of stimulation will be targeted using MRI&#xD;
      co-registration. The study seeks to determine if the bilateral theta burst protocol has&#xD;
      similar effectiveness to the conventional bilateral rTMS protocol in treating major&#xD;
      depression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Anticipated">September 2023</completion_date>
  <primary_completion_date type="Anticipated">March 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change on the Montgomery Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>After 4 or 6 weeks</time_frame>
    <description>Change from baseline to week 4 or 6 endpoint</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Remission on the MADRS</measure>
    <time_frame>After 4 or 6 weeks</time_frame>
    <description>Score less than or equal to 10</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">163</enrollment>
  <condition>Major Depression</condition>
  <arm_group>
    <arm_group_label>Convential Sequential Bilateral rTMS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>LFR followed by HFL.&#xD;
1 Hz stimulation of the right DLPFC for 600 pulses followed by 10 Hz stimulation of the left DLPFC for 3000 pulses (4 seconds on 26 seconds off for 75 trains). Treatment will occur 5 times per week for 4 to 6 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bilateral Theta Burst Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>cTBS followed by iTBS.&#xD;
continuous theta burst stimulation (cTBS) of the right DLPFC for 600 pulses followed by intermittent theta burst stimulation (iTBS) of the left DLPFC for 600 pulses. Treatment will occur 5 times per week for 4 to 6 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>LFR followed by HFL</intervention_name>
    <description>Magventure Cool B70 Coil with RX100 Stimulator</description>
    <arm_group_label>Convential Sequential Bilateral rTMS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>cTBS followed by iTBS</intervention_name>
    <description>Magventure Cool B70 Coil with RX100 Stimulator</description>
    <arm_group_label>Bilateral Theta Burst Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  are an outpatient&#xD;
&#xD;
          -  are ≥60 years old&#xD;
&#xD;
          -  have a Mini-International Neuropsychiatric Interview (MINI 6.0)67 confirmed diagnosis&#xD;
             of MDD, with a current MDE&#xD;
&#xD;
          -  have failed to achieve a clinical response to an adequate dose of an antidepressant&#xD;
             based on an Antidepressant Treatment History Form (ATHF) score of &gt; 3 in the current&#xD;
             episode or have failed to tolerate two separate trials of an antidepressant&#xD;
&#xD;
          -  have a score &gt; 17 on the MADRS&#xD;
&#xD;
          -  have had no increase or initiation of any psychotropic medication in the 4 weeks prior&#xD;
             to screening&#xD;
&#xD;
          -  have normal electrolytes, hemoglobin and thyroid functioning based on pre-study blood&#xD;
             work&#xD;
&#xD;
          -  Pass the TMS adult safety screening (TASS) questionnaire&#xD;
&#xD;
          -  Are able to have an MRI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  have a history of substance dependence or abuse within the last 3 months&#xD;
&#xD;
          -  have a concomitant major unstable medical illness determined by one of the study&#xD;
             physicians&#xD;
&#xD;
          -  have active suicidal intent&#xD;
&#xD;
          -  have a lifetime MINI diagnosis of bipolar I or II disorder, or primary psychotic&#xD;
             disorder&#xD;
&#xD;
          -  have current psychotic symptoms&#xD;
&#xD;
          -  have a diagnosis of obsessive compulsive disorder, post-traumatic stress disorder&#xD;
             (current or within the last year), anxiety disorder (generalized anxiety disorder,&#xD;
             social anxiety disorder, panic disorder), or dysthymia, assessed by a study&#xD;
             investigator to be primary. One of these comorbidities will not be exclusionary if&#xD;
             they are not deemed to be primary.&#xD;
&#xD;
          -  have a diagnosis of any personality disorder, and assessed by a study investigator to&#xD;
             be primary and causing greater impairment than MDD&#xD;
&#xD;
          -  have presumed or probable dementia or clinical evidence of dementia as assessed by a&#xD;
             Short Blessed Test score of greater than 10.&#xD;
&#xD;
          -  did not respond to a course of ECT in the current depressive episode&#xD;
&#xD;
          -  have received rTMS in the current episode, patients who have had rTMS in a previous&#xD;
             episode would be eligible&#xD;
&#xD;
          -  have a history of a primary seizure disorder or a seizure associated with an&#xD;
             intracranial lesion.&#xD;
&#xD;
          -  have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear&#xD;
             implants, or electrodes) or any other metal object within or near the head, excluding&#xD;
             the mouth, that cannot be safely removed&#xD;
&#xD;
          -  have a implanted electronic device that is currently function such as a defibrillator&#xD;
&#xD;
          -  currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an&#xD;
             anticonvulsant&#xD;
&#xD;
          -  if participating in psychotherapy, must have been in stable treatment for at least 3&#xD;
             months prior to entry into the study, with no anticipation of change in the frequency&#xD;
             of therapeutic sessions, or the therapeutic focus over the duration of the study&#xD;
&#xD;
          -  non-correctable clinically significant sensory impairment (i.e., cannot hear well&#xD;
             enough to cooperate with interview).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel M. Blumberger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CAMH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CAMH</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M6J1H4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.camh.net/research</url>
    <description>Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collab</description>
  </link>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>February 10, 2022</last_update_submitted>
  <last_update_submitted_qc>February 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for Addiction and Mental Health</investigator_affiliation>
    <investigator_full_name>Daniel Blumberger</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>late-life depression</keyword>
  <keyword>treatment resistance</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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The study protocol and statistical analysis plan will be made available. Individual patient data will be made available once all primary and secondary analyses have been conducted by the study team.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>Individual patient data will be made available once all primary and secondary analyses have been conducted by the study team.</ipd_time_frame>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02998580
org study id: 076-2016
nct id: NCT02998580
lead sponsor: 
collaborator: 
has dmc: No
This trial will compare conventional sequential bilateral rTMS to a bilateral theta burst
      stimulation protocol. The right and left dorsolateral prefrontal cortices will be the site of
      stimulation in both treatment conditions. The site of stimulation will be targeted using MRI
      co-registration. The study seeks to determine if the bilateral theta burst protocol has
      similar effectiveness to the conventional bilateral rTMS protocol in treating major
      depression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change on the Montgomery Asberg Depression Rating Scale (MADRS)
time frame: After 4 or 6 weeks
description: Change from baseline to week 4 or 6 endpoint
measure: Remission on the MADRS
time frame: After 4 or 6 weeks
description: Score less than or equal to 10
arm group label: Convential Sequential Bilateral rTMS
arm group type: Active Comparator
description: LFR followed by HFL.
1 Hz stimulation of the right DLPFC for 600 pulses followed by 10 Hz stimulation of the left DLPFC for 3000 pulses (4 seconds on 26 seconds off for 75 trains). Treatment will occur 5 times per week for 4 to 6 weeks.
arm group label: Bilateral Theta Burst Stimulation
arm group type: Experimental
description: cTBS followed by iTBS.
continuous theta burst stimulation (cTBS) of the right DLPFC for 600 pulses followed by intermittent theta burst stimulation (iTBS) of the left DLPFC for 600 pulses. Treatment will occur 5 times per week for 4 to 6 weeks.
intervention type: Device
intervention name: LFR followed by HFL
description: Magventure Cool B70 Coil with RX100 Stimulator
arm group label: Convential Sequential Bilateral rTMS
intervention type: Device
intervention name: cTBS followed by iTBS
description: Magventure Cool B70 Coil with RX100 Stimulator
arm group label: Bilateral Theta Burst Stimulation
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Daniel M. Blumberger, MD
role: Principal Investigator
affiliation: CAMH
facility: 
country: Canada
url: http://www.camh.net/research
description: Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collab
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Daniel Blumberger
investigator title: Principal Investigator
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: Yes
ipd description: The study protocol and statistical analysis plan will be made available. Individual patient data will be made available once all primary and secondary analyses have been conducted by the study team.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: Individual patient data will be made available once all primary and secondary analyses have been conducted by the study team.