<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/NCT03287037</url>
  </required_header>
  <id_info>
    <org_study_id>2-103-03-002-1</org_study_id>
    <nct_id>NCT03287037</nct_id>
  </id_info>
  <brief_title>The Effects of tDCS on Depressive Symptoms,Neurocognitive Function and HRV in Unipolar Depression and Bipolar Depression</brief_title>
  <official_title>To Investigate the Effect of Transcranial Direct Current Stimulation (tDCS) on Depressive Symptoms, Neurocognitive Function and Heart Rate Variability in Unipolar Depression and Bipolar Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tri-Service General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tri-Service General 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>
      The study aimed to investigate whether transcranial direct current stimulation could improve&#xD;
      depressive symptoms, neurocognitive function and modulate heart rate variability in unipolar&#xD;
      and bipolar depression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      Transcranial direct current stimulation encompasses the induction of a relatively weak&#xD;
      constant current flow through the cerebral cortex via scalp electrodes . Dependent on&#xD;
      stimulation polarity, this results in a modulation of cortical excitability and spontaneous&#xD;
      neural activity. The technique was established in the 1950s and 1960s primarily in animals.&#xD;
      In these early studies it was shown that subthreshold DC stimulation increases spontaneous&#xD;
      neuronal activity if the anode is placed above or within the cortex, while exposure to&#xD;
      cathodal polarity results in reduced activity. This is caused by a subthreshold membrane&#xD;
      depolarization by anodal and a hyperpolarization by cathodal stimulation. It was demonstrated&#xD;
      in humans that the after-effects of tDCS depend on modifications of NMDA receptor-efficacy.&#xD;
      The after-effects of tDCS are blocked by the NMDA receptor antagonist dextromethorphan, and&#xD;
      prolonged by the partial NMDA receptor-agonist D-cycloserine. This tDCS polarity-dependent&#xD;
      alteration of NMDA receptor function seems to be initiated by the respective membrane&#xD;
      potential shift and probably by the accompanying cortical activity modification,because it is&#xD;
      prevented by the sodium channel blocker carbamazepine. Intraneuronal calcium concentration&#xD;
      also contributes, because calcium channel antagonists eliminate the excitability-enhancing&#xD;
      after-effects of anodal tDCS. Recently, tDCS has been reported to be a novel, non-invasive&#xD;
      and safe therapeutic tool to treat neuropsychiatric disorders including depression. This&#xD;
      therapeutic tool has been reported to show promising effect in treating unipolar and bipolar&#xD;
      depression. However, the sample sizes have been small. Further work is needed to see if these&#xD;
      early promising studies replicate. Much evidence has indicated that patients with depression&#xD;
      show hypoactivity over left dorsolateral prefrontal cortex (DLPFC) and hyperactivity over&#xD;
      right DLPFC. We therefore hypothesize that tDCS over DLPFC with anode placed at left DLPFC&#xD;
      and cathode placed at right DLPFC would reduce depressive symptoms in patients with unipolar&#xD;
      depression and bipolar depression.&#xD;
&#xD;
      The study aimed to investigate whether tDCS over DLPFC could modify depressive symptoms,&#xD;
      neurocognitive function and heart rate variability of unipolar and bipolar depression.&#xD;
&#xD;
      Study design: open-label study.&#xD;
&#xD;
      Participants: 60 patients with unipolar depression and 60 with bipolar depression.&#xD;
&#xD;
      Others: see Arms and Interventions, Eligibility Criteria or Outcome Measures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2016</start_date>
  <completion_date type="Actual">September 6, 2019</completion_date>
  <primary_completion_date type="Actual">September 6, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Sixty patients with unipolar depression (major depressive disorder) and 60 with bipolar depression were treated with 10 sessions of tDCS.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes from baseline score of Hamilton Depression Rating Scale (HAM-D) at the timepoint immediately after tDCS, at one week and one month after tDCS</measure>
    <time_frame>One month</time_frame>
    <description>Depression severity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline score of Young Mania Rating Scale (YMRS) at the timepoint immediately after tDCS, at one week and one month after tDCS</measure>
    <time_frame>One month</time_frame>
    <description>Hypomania/mania severity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline score of Hamilton Anxiety Rating Scale (HAM-A) at the timepoint immediately after tDCS, at one week and one month after tDCS</measure>
    <time_frame>One month</time_frame>
    <description>Anxiety severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from basline heart rate variability (HRV) at the timepoint immediately after tDCS, at one week and one month after tDCS</measure>
    <time_frame>One month</time_frame>
    <description>Index of autonomic functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline results of continuous performance test (CPT) at the timepoint immediately after tDCS, at one week and one month after tDCS</measure>
    <time_frame>One month</time_frame>
    <description>Performance of prefrontal-mediated task.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Depressive Disorder, Major</condition>
  <condition>Depression, Bipolar</condition>
  <condition>Electricity; Effects</condition>
  <arm_group>
    <arm_group_label>tDCS over DLPFC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Direct current (DC) generated by a DC stimulator (Eldith DC stimulator: www. neuroconn.de/dc-stimulator_plus_en/) was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 cm2). The anodal electrode was placed over the left dorsolateral prefrontal cortex (F3, International EEG System 10-20) and cathode electrode over F4. Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>tDCS over DLPFC</intervention_name>
    <description>We applied tDCS over dorsolateral prefrontal cortex (DLPFC) for these depressed patients. Direct current (DC) generated by a DC stimulator (Eldith DC stimulator: www. neuroconn.de/dc-stimulator_plus_en/) was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 cm2). The anodal electrode was placed over the left dorsolateral prefrontal cortex (F3, International EEG System 10-20) and cathode electrode over F4. Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours. All patients were maintained on their treatment throughout the study period.</description>
    <arm_group_label>tDCS over DLPFC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients who met DSM-IV-TR criteria for major depressive disorder and bipolar depression&#xD;
        and had moderate to severe depression severity (HAM-D score more than 17) were included in&#xD;
        the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. pregnancy or breastfeeding.&#xD;
&#xD;
          2. having epilepsy, severe physical illness, any current psychiatric comorbidity or&#xD;
             history of substance dependence.&#xD;
&#xD;
          3. having contraindications for transcranial electrical/magnetic stimulation.&#xD;
&#xD;
          4. having intracranial metal foreign bodies.&#xD;
&#xD;
          5. having a history of intracranial neoplasms or surgery, or a history of severe head&#xD;
             injuries or cerebrovascular diseases.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hsin-An Chang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tri-Service General Hospital, National Defense Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tri-service general hospital</name>
      <address>
        <city>Taipei</city>
        <zip>114</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <last_update_submitted>September 27, 2019</last_update_submitted>
  <last_update_submitted_qc>September 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tri-Service General Hospital</investigator_affiliation>
    <investigator_full_name>Hsin-An Chang, MD</investigator_full_name>
    <investigator_title>Head of Laboratory of Psychophysiology, Department of Psychiatry, Principal Investigator, Attending Psychiatrist, Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Unipolar depression</keyword>
  <keyword>bipolar depression</keyword>
  <keyword>Transcranial direct current stimulation</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>Bipolar 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/NCT03287037
org study id: 2-103-03-002-1
nct id: NCT03287037
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study aimed to investigate whether transcranial direct current stimulation could improve
      depressive symptoms, neurocognitive function and modulate heart rate variability in unipolar
      and bipolar depression.
Background

      Transcranial direct current stimulation encompasses the induction of a relatively weak
      constant current flow through the cerebral cortex via scalp electrodes . Dependent on
      stimulation polarity, this results in a modulation of cortical excitability and spontaneous
      neural activity. The technique was established in the 1950s and 1960s primarily in animals.
      In these early studies it was shown that subthreshold DC stimulation increases spontaneous
      neuronal activity if the anode is placed above or within the cortex, while exposure to
      cathodal polarity results in reduced activity. This is caused by a subthreshold membrane
      depolarization by anodal and a hyperpolarization by cathodal stimulation. It was demonstrated
      in humans that the after-effects of tDCS depend on modifications of NMDA receptor-efficacy.
      The after-effects of tDCS are blocked by the NMDA receptor antagonist dextromethorphan, and
      prolonged by the partial NMDA receptor-agonist D-cycloserine. This tDCS polarity-dependent
      alteration of NMDA receptor function seems to be initiated by the respective membrane
      potential shift and probably by the accompanying cortical activity modification,because it is
      prevented by the sodium channel blocker carbamazepine. Intraneuronal calcium concentration
      also contributes, because calcium channel antagonists eliminate the excitability-enhancing
      after-effects of anodal tDCS. Recently, tDCS has been reported to be a novel, non-invasive
      and safe therapeutic tool to treat neuropsychiatric disorders including depression. This
      therapeutic tool has been reported to show promising effect in treating unipolar and bipolar
      depression. However, the sample sizes have been small. Further work is needed to see if these
      early promising studies replicate. Much evidence has indicated that patients with depression
      show hypoactivity over left dorsolateral prefrontal cortex (DLPFC) and hyperactivity over
      right DLPFC. We therefore hypothesize that tDCS over DLPFC with anode placed at left DLPFC
      and cathode placed at right DLPFC would reduce depressive symptoms in patients with unipolar
      depression and bipolar depression.

      The study aimed to investigate whether tDCS over DLPFC could modify depressive symptoms,
      neurocognitive function and heart rate variability of unipolar and bipolar depression.

      Study design: open-label study.

      Participants: 60 patients with unipolar depression and 60 with bipolar depression.

      Others: see Arms and Interventions, Eligibility Criteria or Outcome Measures.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Sixty patients with unipolar depression (major depressive disorder) and 60 with bipolar depression were treated with 10 sessions of tDCS.
primary purpose: Treatment
masking: None (Open Label)
measure: Changes from baseline score of Hamilton Depression Rating Scale (HAM-D) at the timepoint immediately after tDCS, at one week and one month after tDCS
time frame: One month
description: Depression severity
measure: Changes from baseline score of Young Mania Rating Scale (YMRS) at the timepoint immediately after tDCS, at one week and one month after tDCS
time frame: One month
description: Hypomania/mania severity
measure: Changes from baseline score of Hamilton Anxiety Rating Scale (HAM-A) at the timepoint immediately after tDCS, at one week and one month after tDCS
time frame: One month
description: Anxiety severity.
measure: Changes from basline heart rate variability (HRV) at the timepoint immediately after tDCS, at one week and one month after tDCS
time frame: One month
description: Index of autonomic functioning.
measure: Changes from baseline results of continuous performance test (CPT) at the timepoint immediately after tDCS, at one week and one month after tDCS
time frame: One month
description: Performance of prefrontal-mediated task.
arm group label: tDCS over DLPFC
arm group type: Experimental
description: Direct current (DC) generated by a DC stimulator (Eldith DC stimulator: www. neuroconn.de/dc-stimulator_plus_en/) was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 cm2). The anodal electrode was placed over the left dorsolateral prefrontal cortex (F3, International EEG System 10-20) and cathode electrode over F4. Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours.
intervention type: Device
intervention name: tDCS over DLPFC
description: We applied tDCS over dorsolateral prefrontal cortex (DLPFC) for these depressed patients. Direct current (DC) generated by a DC stimulator (Eldith DC stimulator: www. neuroconn.de/dc-stimulator_plus_en/) was bilaterally delivered through a pair of saline-soaked surface sponge electrodes (35 cm2). The anodal electrode was placed over the left dorsolateral prefrontal cortex (F3, International EEG System 10-20) and cathode electrode over F4. Stimulation was applied at an intensity of 2 mA for 20 min, twice-daily on 5 consecutive weekdays. The twice daily sessions were separated by at least 3 hours. All patients were maintained on their treatment throughout the study period.
arm group label: tDCS over DLPFC
criteria: 
gender: All
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: No
last name: Hsin-An Chang, M.D.
role: Principal Investigator
affiliation: Tri-Service General Hospital, National Defense Medical Center
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Tri-Service General Hospital
investigator full name: Hsin-An Chang, MD
investigator title: Head of Laboratory of Psychophysiology, Department of Psychiatry, Principal Investigator, Attending Psychiatrist, Assistant Professor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Bipolar Disorder
mesh term: Depressive Disorder, Major
sharing ipd: No