<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/NCT04486222</url>
  </required_header>
  <id_info>
    <org_study_id>201910101RIND</org_study_id>
    <nct_id>NCT04486222</nct_id>
  </id_info>
  <brief_title>Accelerated Bilateral rTMS on Geriatric Depression</brief_title>
  <official_title>Therapeutic Effect of Accelerated Bilateral Repeated Transcranial Magnetic Stimulation on Geriatric Depression: a Prospective Double-blind, Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Taiwan University Hospital, Yun-Lin Branch</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Taiwan University Hospital</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>
      This study aims to evaluate the efficacy of accelerated bilateral repetitive transcranial&#xD;
      magnetic stimulation (rTMS) on major depression, anxiety, cognitive function and&#xD;
      physiological parameters in elderly depressive patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Repeated transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation&#xD;
      treatment, showing good therapeutic effect to medicine treatment-refractory patients. Recent&#xD;
      studies suggested bilateral DLPFC might be effective to geriatric depression. Accelerated&#xD;
      treatment course was reported to have similar therapeutic effect and safety profile with&#xD;
      traditional course. The investigators hypothesize accelerated bilateral rTMS is effective to&#xD;
      geriatric depression and comorbid anxiety.&#xD;
&#xD;
      Cognitive impairment and decreased parasympathetic tone are common in patients with major&#xD;
      depression. The investigators hypothesize cognitive function and physiological indicators&#xD;
      improve after accelerated bilateral rTMS.&#xD;
&#xD;
      In this single-center, prospective double-blind, randomized, active-controlled trial, the&#xD;
      investigators aim to recruit 100 patients older than 60 years, without neurocognitive&#xD;
      disorders, and refractory to one or more antidepressants. The experimental group would&#xD;
      receive an rTMS course with high-frequency stimulation at left DLPFC followed by&#xD;
      low-frequency inhibition at right DLPFC, two sessions daily, five days a week, and two weeks&#xD;
      in total. The standard treatment group would receive an rTMS course with high-frequency&#xD;
      stimulation at left DLPFC as standard treatment parameters. Mood, cognition and physiological&#xD;
      markers would be monitored every week. The primary outcome is response and remission rate of&#xD;
      major depression measured by Hamilton Rating Scale for Depression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    difficulty in recruiting suitable candidate&#xD;
  </why_stopped>
  <start_date type="Actual">November 23, 2020</start_date>
  <completion_date type="Actual">December 21, 2022</completion_date>
  <primary_completion_date type="Actual">December 21, 2022</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Degree of Change in 17-item Hamilton Depression Rating Scale (HAM-D 17)</measure>
    <time_frame>day 1, day 5, day 12, day 19</time_frame>
    <description>HAM-D 17 is a scale rating the severity of depression, covering emotional, cognitive and somatic symptoms of depression. Higher scores indicate higher severity. Response to treatment is defined as ≥ 50% decrease in HAM-D 17; remission is defined as ≤ 7 points in HAM-D 17.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Degree of Change in Hamilton Anxiety Rating Scale (HAM-A)</measure>
    <time_frame>day 1, day 5, day 12, day 19</time_frame>
    <description>HAM-A is a scale rating the severity of anxiety, covering emotional, cognitive and somatic symptoms of anxiety. Higher scores indicate higher severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Change in Mini-Mental State Examination (MMSE)</measure>
    <time_frame>day 1, day 5, day 12, day 19</time_frame>
    <description>MMSE is a wildly-used tool to evaluate several cognitive function domains.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Change in Stroop Test</measure>
    <time_frame>day 1, day 5, day 12, day 19</time_frame>
    <description>Task 1 (word phase) requests a subject to say a color name string (red, green, blue) printed in black; Task 2 (color phase) requests a subject to say the printed colors (red, green, blue) of letter &quot;x&quot; string; Task 3 (interference phase) requests a subject to say the printed colors of a string of color names (red, green, blue).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Change in Trail Making Test</measure>
    <time_frame>day 1, day 5, day 12, day 19</time_frame>
    <description>Task 1 requests a subject to connect a sequence of 25 consecutive numbers regardless of their colors; Task 2 requires a subject to connect 25 consecutive numbers in alternative colors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Change in Verbal Fluency Test</measure>
    <time_frame>day 1, day 5, day 12, day 19</time_frame>
    <description>This test requests a subject to speak as many names of vegetables, fishes or fruit as possible in 45 seconds.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of Change in Physiological Parameters</measure>
    <time_frame>day 1, day 5, day 12, day 19</time_frame>
    <description>ProComp5 Infiniti (SA7525) Biofeedback System would be used. Heart rate variability, skin conductance, body temperature and respiratory rate would be measured.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Transcranial Magnetic Stimulation</condition>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>Experimental Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The experimental group would receive an rTMS course with high-frequency stimulation (10Hz) at left DLPFC (120% motor threshold, 40 trains, 1600 pulses) followed by low-frequency (1Hz) inhibition at right DLPFC (120% motor threshold, 10 trains, 1200 pulses), two sessions daily with a 1.5-hour inter-session interval (L't active-R't active-1.5 hr-L't active-R't active), five days a week, and two weeks in total.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Treatment Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The standard treatment group would receive an rTMS course with high-frequency stimulation (10Hz) at left DLPFC (120% motor threshold, 40 trains, 1600 pulses) followed by sham inhibition at right DLPFC (1Hz, 10 trains, 1200 pulses); after a 1.5-hour inter-session interval, a sham session would be administered at left and right DLPFC (L't active-R't sham-1.5 hr-L't sham-R't sham. The course would be applied five days a week, and two weeks in total.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Repeated Transcranial Magnetic Stimulation</intervention_name>
    <description>Magstim® Super Rapid² Transcranial Magnetic Stimulation System</description>
    <arm_group_label>Experimental Group</arm_group_label>
    <arm_group_label>Standard Treatment Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age between 60-85 years&#xD;
&#xD;
          -  literate and received basic education for at least 2 years&#xD;
&#xD;
          -  diagnosis of major depressive disorder, without psychotic features, according to DSM-5&#xD;
&#xD;
          -  have a score of 20 or greater on the 17-item Hamilton Depression Rating Scale&#xD;
&#xD;
          -  failed to achieve clinical response by at least 1 antidepressant trial of sufficient&#xD;
             dosage for at least 4 weeks&#xD;
&#xD;
          -  psychoactive agents were in stable doses before randomization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  active suicide plans or attempts; or suicide attempts in the last 12 months&#xD;
&#xD;
          -  diagnosis of schizophrenia or bipolar disorder according to DSM-5&#xD;
&#xD;
          -  have DSM-5-confirmed substance use disorder (excluding tobacco) in the last 3 months&#xD;
&#xD;
          -  have delirium, major neurocognitive disorder or MMSE &lt; 24&#xD;
&#xD;
          -  current use of bupropion &gt;300 mg/day, tricyclic antidepressant, clozapine,&#xD;
             chlorpromazine, foscarnet, ganciclovir, ritonavir, theophylline or anti-epileptic&#xD;
             agents excluding benzodiazepines&#xD;
&#xD;
          -  history of severe head trauma, epilepsy, multiple sclerosis, stroke, brain tumors,&#xD;
             intracranial aneurysm, active intracranial infection, increased intracranial pressure,&#xD;
             metallic implants in the brain, major brain surgery or major neurological diseases&#xD;
&#xD;
          -  with a cardiac pacemaker or defibrillator&#xD;
&#xD;
          -  received rTMS treatment before&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Psychiatry, National Taiwan University Hospital, Yun-Lin Branch</name>
      <address>
        <city>Douliu</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>January 2, 2023</last_update_submitted>
  <last_update_submitted_qc>January 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 4, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>repeated transcranial magnetic stimulation</keyword>
  <keyword>geriatric depression</keyword>
  <keyword>anxiety</keyword>
  <keyword>cognitive impairment</keyword>
  <keyword>heart rate variability</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>
  <!-- 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/NCT04486222
org study id: 201910101RIND
nct id: NCT04486222
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study aims to evaluate the efficacy of accelerated bilateral repetitive transcranial
      magnetic stimulation (rTMS) on major depression, anxiety, cognitive function and
      physiological parameters in elderly depressive patients.
Repeated transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation
      treatment, showing good therapeutic effect to medicine treatment-refractory patients. Recent
      studies suggested bilateral DLPFC might be effective to geriatric depression. Accelerated
      treatment course was reported to have similar therapeutic effect and safety profile with
      traditional course. The investigators hypothesize accelerated bilateral rTMS is effective to
      geriatric depression and comorbid anxiety.

      Cognitive impairment and decreased parasympathetic tone are common in patients with major
      depression. The investigators hypothesize cognitive function and physiological indicators
      improve after accelerated bilateral rTMS.

      In this single-center, prospective double-blind, randomized, active-controlled trial, the
      investigators aim to recruit 100 patients older than 60 years, without neurocognitive
      disorders, and refractory to one or more antidepressants. The experimental group would
      receive an rTMS course with high-frequency stimulation at left DLPFC followed by
      low-frequency inhibition at right DLPFC, two sessions daily, five days a week, and two weeks
      in total. The standard treatment group would receive an rTMS course with high-frequency
      stimulation at left DLPFC as standard treatment parameters. Mood, cognition and physiological
      markers would be monitored every week. The primary outcome is response and remission rate of
      major depression measured by Hamilton Rating Scale for Depression.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Degree of Change in 17-item Hamilton Depression Rating Scale (HAM-D 17)
time frame: day 1, day 5, day 12, day 19
description: HAM-D 17 is a scale rating the severity of depression, covering emotional, cognitive and somatic symptoms of depression. Higher scores indicate higher severity. Response to treatment is defined as ≥ 50% decrease in HAM-D 17; remission is defined as ≤ 7 points in HAM-D 17.
measure: Degree of Change in Hamilton Anxiety Rating Scale (HAM-A)
time frame: day 1, day 5, day 12, day 19
description: HAM-A is a scale rating the severity of anxiety, covering emotional, cognitive and somatic symptoms of anxiety. Higher scores indicate higher severity.
measure: Degree of Change in Mini-Mental State Examination (MMSE)
time frame: day 1, day 5, day 12, day 19
description: MMSE is a wildly-used tool to evaluate several cognitive function domains.
measure: Degree of Change in Stroop Test
time frame: day 1, day 5, day 12, day 19
description: Task 1 (word phase) requests a subject to say a color name string (red, green, blue) printed in black; Task 2 (color phase) requests a subject to say the printed colors (red, green, blue) of letter "x" string; Task 3 (interference phase) requests a subject to say the printed colors of a string of color names (red, green, blue).
measure: Degree of Change in Trail Making Test
time frame: day 1, day 5, day 12, day 19
description: Task 1 requests a subject to connect a sequence of 25 consecutive numbers regardless of their colors; Task 2 requires a subject to connect 25 consecutive numbers in alternative colors.
measure: Degree of Change in Verbal Fluency Test
time frame: day 1, day 5, day 12, day 19
description: This test requests a subject to speak as many names of vegetables, fishes or fruit as possible in 45 seconds.
measure: Degree of Change in Physiological Parameters
time frame: day 1, day 5, day 12, day 19
description: ProComp5 Infiniti (SA7525) Biofeedback System would be used. Heart rate variability, skin conductance, body temperature and respiratory rate would be measured.
arm group label: Experimental Group
arm group type: Experimental
description: The experimental group would receive an rTMS course with high-frequency stimulation (10Hz) at left DLPFC (120% motor threshold, 40 trains, 1600 pulses) followed by low-frequency (1Hz) inhibition at right DLPFC (120% motor threshold, 10 trains, 1200 pulses), two sessions daily with a 1.5-hour inter-session interval (L't active-R't active-1.5 hr-L't active-R't active), five days a week, and two weeks in total.
arm group label: Standard Treatment Group
arm group type: Active Comparator
description: The standard treatment group would receive an rTMS course with high-frequency stimulation (10Hz) at left DLPFC (120% motor threshold, 40 trains, 1600 pulses) followed by sham inhibition at right DLPFC (1Hz, 10 trains, 1200 pulses); after a 1.5-hour inter-session interval, a sham session would be administered at left and right DLPFC (L't active-R't sham-1.5 hr-L't sham-R't sham. The course would be applied five days a week, and two weeks in total.
intervention type: Device
intervention name: Repeated Transcranial Magnetic Stimulation
description: Magstim® Super Rapid² Transcranial Magnetic Stimulation System
arm group label: Experimental Group
arm group label: Standard Treatment Group
criteria: 
gender: All
minimum age: 60 Years
maximum age: 85 Years
healthy volunteers: No
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
sharing ipd: No