<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/NCT03257397</url>
  </required_header>
  <id_info>
    <org_study_id>PSY-NIL-0008</org_study_id>
    <nct_id>NCT03257397</nct_id>
  </id_info>
  <brief_title>TBS in Major Depression</brief_title>
  <official_title>Theta-burst Transcranial Magnetic Stimulation for the Treatment of Major Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rupert Lanzenberger</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Vienna</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background Major depression is associated with morbidity and increased mortality. Along with&#xD;
      the psychological strain depression represents a high socioeconomic burden costing Europe&#xD;
      more than €113 billion/year. About one third of patients do not respond to appropriate&#xD;
      therapy. Theta-burst stimulation (TBS), a form of transcranial magnetic stimulation is an&#xD;
      emerging treatment for patients for whom pharmacological treatment is ineffective or not&#xD;
      appropriate. Based on two different theories of prefrontal dysfunction two TBS-protocols&#xD;
      should have the most antidepressant effects. However, no study so far has compared the two&#xD;
      approaches or systematically investigated their differential effects on brain function and on&#xD;
      a symptom level.&#xD;
&#xD;
      Objectives of the study The aim of this study is to test two TBS protocols on symptom&#xD;
      improvement and associated brain function in patients with treatment resistant depression&#xD;
      (TRD): iTBS over bilateral DLPFC and iTBS over left and cTBS over right DLPFC. As stimulation&#xD;
      over non-motor regions offers no direct readout, fMRI at baseline and after treatment will be&#xD;
      harnessed to quantify an effect on brain activity and functional network metrics.&#xD;
&#xD;
      Study population 80 patients with TRD will be enrolled with 40 patients receiving the one,&#xD;
      and 40 patients receiving the other TBS protocol for a treatment period of three weeks.&#xD;
&#xD;
      Study design The study is designed as a longitudinal, randomized and double-blind clinical&#xD;
      trial. At baseline and after treatment, patients will undergo psychiatric testing using&#xD;
      several symptom scales including the Hamilton Depression Rating Scale (HAMD-17), the Beck&#xD;
      Depression Inventory (BDI-II), the Inventory of Depressive Symptomatology (IDS-C) and the&#xD;
      State-Trait Anxiety Inventory (STAI). Changes in HAMD-17 scores are defined as primary&#xD;
      endpoint. Moreover MRI scans before and after treatment will include structural and&#xD;
      functional MRI sequences as well as diffusion weighted imaging (DWI) sequence. Functional&#xD;
      connectivity and BOLD responses will serve as primary imaging endpoints. A follow-up visit 2&#xD;
      weeks and a final examination 4 weeks after treatment will elucidate durability of effects.&#xD;
&#xD;
      Relevance and implications of the study By investigating which approach is superior for which&#xD;
      symptoms our study will contribute to the development of personalized treatment, the&#xD;
      reduction of personal suffering and the reduction of costs and occupational disability.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2020</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>HAMD</measure>
    <time_frame>&lt;1 month</time_frame>
    <description>Hamilton depression rating scale</description>
  </primary_outcome>
  <primary_outcome>
    <measure>BDI-II</measure>
    <time_frame>&lt;1 month</time_frame>
    <description>Beck Depression Inventory</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Regional white matter microstructure using DWI</measure>
    <time_frame>&lt;1 month</time_frame>
    <description>White matter microstructure will be investigated using diffusion tensor imaging and analyzed using tract-based spatial statistics and tractography</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Regional grey matter volume and using MRI</measure>
    <time_frame>&lt;1 month</time_frame>
    <description>Regional grey matter volume will be investigated using voxel-based morphometry</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Global physical activity</measure>
    <time_frame>&lt;1 month</time_frame>
    <description>assessed using Clinical Global Impression Scale (CGI-S)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Treatment Resistant Depression</condition>
  <arm_group>
    <arm_group_label>left iTBS and right cTBS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>40 patients will receive intermittent theta-burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS (cTBS) over the right DLPFC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>left and right iTBS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>40 patients will receive intermittent theta-burst stimulation (iTBS) over the left and right dorsolateral prefrontal cortex (DLPFC)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>theta-burst stimulation (TBS) using a MagPro X1000</intervention_name>
    <description>iTBS over left and cTBS over right dorsolateral prefrontal cortex for a period of three weeks. iTBS: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. cTBS: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in a single 40s train; one session will comprise left iTBS and right cTBS. There will be two sessions daily with 60 min in between sessions</description>
    <arm_group_label>left iTBS and right cTBS</arm_group_label>
    <other_name>transcranial magnetic stimulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>theta-burst stimulation (TBS) using a MagPro X1000</intervention_name>
    <description>iTBS over left and right dorsolateral prefrontal cortex for a period of three weeks. iTBS consists of 3-pulse 50 Hz bursts which will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. One session will comprise left and right iTBS. There will be two sessions daily with 60 min in between sessions</description>
    <arm_group_label>left and right iTBS</arm_group_label>
    <other_name>transcranial magnetic stimulation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  DSM-5 diagnosis of a single or recurrent major depression&#xD;
&#xD;
          -  Failure of at least two adequate antidepressant treatments&#xD;
&#xD;
          -  HAMD-17 total score of ≥ 23 and a Clinical Global Impression Scale (CGI-S) of ≥ 4&#xD;
&#xD;
          -  Stable psychopharmacological treatment within 2 weeks prior inclusion&#xD;
&#xD;
          -  Age 18-65 years&#xD;
&#xD;
          -  Right-handedness (assessed with the Edinburgh Handedness Inventory)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Seizures in medical history&#xD;
&#xD;
          -  Medical history of major systemic illness, neurological disorders and previous brain&#xD;
             injuries&#xD;
&#xD;
          -  Ferromagnetic implants, cardiac pacemaker, deep brain stimulation and other common MRI&#xD;
             and TMS exclusion criteria&#xD;
&#xD;
          -  Current psychotic symptoms&#xD;
&#xD;
          -  Substance abuse or dependence within last 3 months&#xD;
&#xD;
          -  Borderline personality disorder (based on DSM-5 criteria)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Active suicidal intent&#xD;
&#xD;
          -  Benzodiazepines other than Lorazepam &lt; 2mg/d&#xD;
&#xD;
          -  failure to comply with the study protocol or to follow the instructions of the&#xD;
             investigating team&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Georg S Kranz, PhD</last_name>
    <phone>+43 1 40400</phone>
    <phone_ext>38250</phone_ext>
    <email>georg.kranz@meduniwien.ac.at</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rupert Lanzenberger, Assoc.Prof</last_name>
    <phone>+43 1 40400</phone>
    <phone_ext>35760</phone_ext>
    <email>rupert.lanzenberger@meduniwien.ac.at</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Psychiatry and Psychotherapy, Medical University of Vienna</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rupert Lanzenberger, A/Prof.</last_name>
      <phone>+43 40400</phone>
      <phone_ext>3825</phone_ext>
      <email>rupert.lanzenberger@meduniwien.ac.at</email>
    </contact>
    <investigator>
      <last_name>Rupert Lanzenberger, A/Prof. MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <last_update_submitted>March 11, 2019</last_update_submitted>
  <last_update_submitted_qc>March 11, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Vienna</investigator_affiliation>
    <investigator_full_name>Rupert Lanzenberger</investigator_full_name>
    <investigator_title>Assoc.-Prof. PD Dr.</investigator_title>
  </responsible_party>
  <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, Treatment-Resistant</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </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/NCT03257397
org study id: PSY-NIL-0008
nct id: NCT03257397
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background Major depression is associated with morbidity and increased mortality. Along with
      the psychological strain depression represents a high socioeconomic burden costing Europe
      more than €113 billion/year. About one third of patients do not respond to appropriate
      therapy. Theta-burst stimulation (TBS), a form of transcranial magnetic stimulation is an
      emerging treatment for patients for whom pharmacological treatment is ineffective or not
      appropriate. Based on two different theories of prefrontal dysfunction two TBS-protocols
      should have the most antidepressant effects. However, no study so far has compared the two
      approaches or systematically investigated their differential effects on brain function and on
      a symptom level.

      Objectives of the study The aim of this study is to test two TBS protocols on symptom
      improvement and associated brain function in patients with treatment resistant depression
      (TRD): iTBS over bilateral DLPFC and iTBS over left and cTBS over right DLPFC. As stimulation
      over non-motor regions offers no direct readout, fMRI at baseline and after treatment will be
      harnessed to quantify an effect on brain activity and functional network metrics.

      Study population 80 patients with TRD will be enrolled with 40 patients receiving the one,
      and 40 patients receiving the other TBS protocol for a treatment period of three weeks.

      Study design The study is designed as a longitudinal, randomized and double-blind clinical
      trial. At baseline and after treatment, patients will undergo psychiatric testing using
      several symptom scales including the Hamilton Depression Rating Scale (HAMD-17), the Beck
      Depression Inventory (BDI-II), the Inventory of Depressive Symptomatology (IDS-C) and the
      State-Trait Anxiety Inventory (STAI). Changes in HAMD-17 scores are defined as primary
      endpoint. Moreover MRI scans before and after treatment will include structural and
      functional MRI sequences as well as diffusion weighted imaging (DWI) sequence. Functional
      connectivity and BOLD responses will serve as primary imaging endpoints. A follow-up visit 2
      weeks and a final examination 4 weeks after treatment will elucidate durability of effects.

      Relevance and implications of the study By investigating which approach is superior for which
      symptoms our study will contribute to the development of personalized treatment, the
      reduction of personal suffering and the reduction of costs and occupational disability.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: HAMD
time frame: <1 month
description: Hamilton depression rating scale
measure: BDI-II
time frame: <1 month
description: Beck Depression Inventory
measure: Regional white matter microstructure using DWI
time frame: <1 month
description: White matter microstructure will be investigated using diffusion tensor imaging and analyzed using tract-based spatial statistics and tractography
measure: Regional grey matter volume and using MRI
time frame: <1 month
description: Regional grey matter volume will be investigated using voxel-based morphometry
measure: Global physical activity
time frame: <1 month
description: assessed using Clinical Global Impression Scale (CGI-S)
arm group label: left iTBS and right cTBS
arm group type: Experimental
description: 40 patients will receive intermittent theta-burst stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS (cTBS) over the right DLPFC
arm group label: left and right iTBS
arm group type: Active Comparator
description: 40 patients will receive intermittent theta-burst stimulation (iTBS) over the left and right dorsolateral prefrontal cortex (DLPFC)
intervention type: Device
intervention name: theta-burst stimulation (TBS) using a MagPro X1000
description: iTBS over left and cTBS over right dorsolateral prefrontal cortex for a period of three weeks. iTBS: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. cTBS: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in a single 40s train; one session will comprise left iTBS and right cTBS. There will be two sessions daily with 60 min in between sessions
arm group label: left iTBS and right cTBS
other name: transcranial magnetic stimulation
intervention type: Device
intervention name: theta-burst stimulation (TBS) using a MagPro X1000
description: iTBS over left and right dorsolateral prefrontal cortex for a period of three weeks. iTBS consists of 3-pulse 50 Hz bursts which will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. One session will comprise left and right iTBS. There will be two sessions daily with 60 min in between sessions
arm group label: left and right iTBS
other name: transcranial magnetic stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Georg S Kranz, PhD
phone: +43 1 40400
phone ext: 38250
email: georg.kranz@meduniwien.ac.at
last name: Rupert Lanzenberger, Assoc.Prof
phone: +43 1 40400
phone ext: 35760
email: rupert.lanzenberger@meduniwien.ac.at
facility: 
status: Recruiting
contact: 
investigator: 
country: Austria
responsible party type: Sponsor-Investigator
investigator affiliation: Medical University of Vienna
investigator full name: Rupert Lanzenberger
investigator title: Assoc.-Prof. PD Dr.
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
sharing ipd: Undecided