<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/NCT04497493</url>
  </required_header>
  <id_info>
    <org_study_id>tDCS-2020-TJAH</org_study_id>
    <nct_id>NCT04497493</nct_id>
  </id_info>
  <brief_title>Efficacy of Transcranial Direct Current Stimulation (tDCS) for the Treatment of Major Depressive Disorder</brief_title>
  <official_title>Efficacy of Transcranial Direct Current Stimulation (tDCS) of Dorsolateral-prefrontal Cortex as an Add-on Treatment for Drug-naïve Major Depressive Disorder: A Randomized, Double-blind, Sham-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tianjin Anding Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tianjin Anding Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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 aim of this study is to assess the efficacy of Transcranial Direct Current Stimulation&#xD;
      (tDCS) as an Add-on Treatment for the drug-naïve Major depressive disorder. Meanwhile,&#xD;
      evaluate the effect of tDCS on cognitive function of drug-naïve MDD patients. Furthermore,&#xD;
      the investigators will examine the changes in cortisol, gut microbiome and some biomarkers.&#xD;
      The hypothesis of this study is that tDCS alleviate the depressive symptoms and improve the&#xD;
      cognitive function of drug-naïve Major depressive disorder patients with regulating&#xD;
      inflammatory response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, sham-controlled study using transcranial Direct Current&#xD;
      Stimulation (tDCS) for 4-week treatment. After the intervention of tDCS, there is a follow up&#xD;
      visit at week 8 in order to understand the long-term effects of tDCS. Participants were&#xD;
      randomly assigned 1:1 to tDCS group or sham-control group. Active tDCS comprised 20 min&#xD;
      sessions of 2 mA direct current delivered over the dorsolateral prefrontal cortex, 5 days per&#xD;
      week, for 4 weeks. Sham was administered similarly, but with current turned off after 30s.&#xD;
      Apart from studying the effects of tDCS on severity of depression and cognitive function, the&#xD;
      secondary outcomes are to examine biomarkers related to inflammatory activity. Scale&#xD;
      assessments are performed before the initiation of treatment, week 1, week 2, week 3, week 4&#xD;
      and week8. Collection of blood, excrement and saliva takes place at three time points, at the&#xD;
      baseline, week 4 and week 8.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 22, 2020</start_date>
  <completion_date type="Anticipated">March 2023</completion_date>
  <primary_completion_date type="Anticipated">October 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, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The change of scores in Hamilton Depression Rating Scale (HAMD)-17 from baseline to week 4.</measure>
    <time_frame>baseline, Week 1, week 2, week 3, week 4</time_frame>
    <description>The main objective is to explore whether tDCS add on SSRI or SNRI will improve the MDD symptoms after 4 weeks of treatment, and investigators assess the scale at baseline and week 1, 2, 3, 4. Hamilton Depression Rating Scale (HAMD)-17 items was used to evaluate the severity of symptoms of depression. A total score of more than 24 may indicate severe depressive symptoms; A score above 17 may be mild to moderate depressive; If the score is less than 7, the patient has no symptoms of depression. The higher the total score of the scale, the more severe the depressive symptoms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The change of scores in Hamilton Anxiety Rating Scale (HAMA) from baseline to Week 4.</measure>
    <time_frame>baseline, Week 1, week 2, week 3, week 4</time_frame>
    <description>The aim is to explore whether tDCS add on SSRI or SNRI will alleviate the severity of anxious symptoms as measured with HAMA after 4 weeks of treatment, and investigators assess the scale at baseline and week 1, 2, 3, 4. Hamilton Anxiety Rating Scale (HAMA) was used to evaluate the severity of anxiety symptoms and the effects of intervention in patients with anxiety and depressive disorders. The total score ≥ 29 may be severe anxiety; ≥ 21, there may be obvious anxiety; ≥ 14, there may be anxiety; more than 7, there may be anxiety; if less than 7, there will be no anxiety symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change of scores in Pittsburgh Sleep Quality Index (PSQI) from basline to week 8.</measure>
    <time_frame>baseline, Week 4, week8</time_frame>
    <description>The aim is to investigate whether active-stimuli in addition to regular treatment with an antidepressant will improve the sleep quality as measured with Pittsburgh Sleep Quality Index (PSQI) after 4 weeks of treatment compared to sham-stimuli, and investigators assess the scale at baseline and week 4,8. PSQI was used to evaluate the sleep quality of the subjects in the last month. The total score of PSQI ranged from 0 to 21. The higher the score, the worse the sleep quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change of scores in quality of life (QOL) from baseline to week 8.</measure>
    <time_frame>baseline, Week 4, week 8</time_frame>
    <description>The aim is to investigate whether active-stimuli in addition to regular treatment with an antidepressant will improve the quality of life as measured with quality of life (QOL) after 4 weeks of treatment compared to sham-stimuli, and investigators assess the scale at baseline and week 4,8. The QOL scale evaluates the physical health, mental health, social relations and other aspects of the participants. The higher the score is, the better the quality of life is.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change of sores in suicidal risk assessment scale from baseline to week 8</measure>
    <time_frame>baseline, Week 4, week 8</time_frame>
    <description>The aim is to investigate whether active-stimuli in addition to regular treatment with an antidepressant will reduce the risk suicide as measured with the suicidal risk assessment scale after 4 weeks of treatment compared to sham-stimuli, and investigators assess the scale at baseline and week 4,8. The higher the score of the suicidal risk assessment scale, the higher the risk of suicide.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change of scores in Repeatable Battery for the Assessment of neuropsychological Status (Rebans).</measure>
    <time_frame>baseline, Week 4, week 8</time_frame>
    <description>The aim is to observe whether active-stimuli in addition to regular treatment with an antidepressant will improve the cognitive function as measured with Repeatable Battery for the Assessment of Neuropsychological Status (Rebans) after 4 weeks of treatment compared to sham-stimuli, and investigators assess the scale at baseline and week 4,8. The higher the score of the scale, the cognitive function is better.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The changes of levels of biomarkers in peripheral blood from baseline to week 4</measure>
    <time_frame>baseline, week 4</time_frame>
    <description>The aim is to investigate the change of cortisol level of saliva and intestinal flora as active stimuli in addition to regular treatment with an antidepressant after 4 weeks of treatment compared to sham stimuli, and investigators collect the specimens at baseline and week 4.&#xD;
Saliva collection tube to collect saliva, collect naturally discharged saliva in a clean test tube (at least 2ml). Saliva was centrifuged under 1500rpm for 15 minutes and the filtrate was cryopreserved at-80 °C. the saliva was analyzed by ELISA kit.&#xD;
Fecal collection: a) intercept the middle part of the sample with a sterile toothpick or fecal sampler (the surface of feces contains exfoliated cells of intestinal mucosa; the outside is easy to be contaminated, and some bacterial DNA begins to degrade after contact with air), take about the size of peanuts and put them into aseptic 2.0mL centrifuge tubes, 3-5 tubes for each sample are taken for backup，and then put into-80 °C cryopreservation after sub-packaging.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events from baseline to week 4</measure>
    <time_frame>week 1, week 2, week 3, week 4</time_frame>
    <description>The aim is to evaluate the adverse effects during the treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">75</enrollment>
  <condition>Major Depressive Disorders</condition>
  <arm_group>
    <arm_group_label>tDCS group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>participants receive 20 min sessions of 2 mA direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 4 weeks combine a selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitors(SNRI)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Participants receive sham stimulation that administered similarly, but with current turned off after 30s combine a selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitors(SNRI)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Direct Current Stimulation (tDCS)-active</intervention_name>
    <description>Transcranial direct current stimulation (TDC) is a non-invasive neuromodulation technique of the brain with a DC microelectrical stimulator, a cathode electrode and an anode electrode, and a control software to set the output of the stimulation type，participants receive 20 min sessions of 2 mA direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 4 weeks</description>
    <arm_group_label>tDCS group</arm_group_label>
    <other_name>active</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Direct Current Stimulation (tDCS)-sham</intervention_name>
    <description>Transcranial direct current stimulation (TDC) is a non-invasive neuromodulation technique of the brain with a DC microelectrical stimulator, a cathode electrode and an anode electrode, and a control software to set the output of the stimulation type. Participants receive sham stimulation over the dorsolateral prefrontal cortex, with current turned off after 30 second. The session last 20 min 5 days per week, for 4 weeks</description>
    <arm_group_label>Sham group</arm_group_label>
    <other_name>sham</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  a current episode of MDD diagnosed according to Diagnostic and Statistical Manual of&#xD;
             Mental Disorders, Fifth Edition (DSM-5)&#xD;
&#xD;
          -  age between 18 and 50 years&#xD;
&#xD;
          -  a total score of HAMD-17 ≥ 17&#xD;
&#xD;
          -  take antidepressants less than 3 days&#xD;
&#xD;
          -  Patients are compliant with treatment according to the judgement of the treating&#xD;
             clinician.&#xD;
&#xD;
        Participant or guardian has to sign informed consent. The patients' guardians will sign the&#xD;
        informed consent on behalf of the participants when the capacity of participants to consent&#xD;
        is compromised.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A history of manic episode&#xD;
&#xD;
          -  Use of mood stabilizer&#xD;
&#xD;
          -  History of substance abuse or dependence&#xD;
&#xD;
          -  Severe somatic diseases that might interfere with regular antidepressant treatment&#xD;
             including conditions such as kidney and liver failure, uncontrolled hypertension,&#xD;
             cardiovascular, cerebrovascular and pulmonary disease, thyroid disease, diabetes,&#xD;
             epilepsy and asthma.&#xD;
&#xD;
          -  Use of anti-inflammatory medication for longer than 7 days in the last two months&#xD;
             preceding the trial&#xD;
&#xD;
          -  Use of immunosuppressive medication such as oral steroid hormones Women in pregnancy&#xD;
             or lactation period&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jie Li, Doctor</last_name>
    <phone>022-88188006</phone>
    <email>tjlijie3827@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Tianjin Anding Hospital</name>
      <address>
        <city>Tianjin</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jie Li, Doctor</last_name>
      <phone>+86 022 88188006</phone>
      <email>tjlijie3827@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>October 17, 2021</last_update_submitted>
  <last_update_submitted_qc>October 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>drug-naïve Major depressive disorder</keyword>
  <keyword>transcranial Direct Current Stimulation (tDCS)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</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/NCT04497493
org study id: tDCS-2020-TJAH
nct id: NCT04497493
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to assess the efficacy of Transcranial Direct Current Stimulation
      (tDCS) as an Add-on Treatment for the drug-naïve Major depressive disorder. Meanwhile,
      evaluate the effect of tDCS on cognitive function of drug-naïve MDD patients. Furthermore,
      the investigators will examine the changes in cortisol, gut microbiome and some biomarkers.
      The hypothesis of this study is that tDCS alleviate the depressive symptoms and improve the
      cognitive function of drug-naïve Major depressive disorder patients with regulating
      inflammatory response.
This is a randomized, double-blind, sham-controlled study using transcranial Direct Current
      Stimulation (tDCS) for 4-week treatment. After the intervention of tDCS, there is a follow up
      visit at week 8 in order to understand the long-term effects of tDCS. Participants were
      randomly assigned 1:1 to tDCS group or sham-control group. Active tDCS comprised 20 min
      sessions of 2 mA direct current delivered over the dorsolateral prefrontal cortex, 5 days per
      week, for 4 weeks. Sham was administered similarly, but with current turned off after 30s.
      Apart from studying the effects of tDCS on severity of depression and cognitive function, the
      secondary outcomes are to examine biomarkers related to inflammatory activity. Scale
      assessments are performed before the initiation of treatment, week 1, week 2, week 3, week 4
      and week8. Collection of blood, excrement and saliva takes place at three time points, at the
      baseline, week 4 and week 8.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: The change of scores in Hamilton Depression Rating Scale (HAMD)-17 from baseline to week 4.
time frame: baseline, Week 1, week 2, week 3, week 4
description: The main objective is to explore whether tDCS add on SSRI or SNRI will improve the MDD symptoms after 4 weeks of treatment, and investigators assess the scale at baseline and week 1, 2, 3, 4. Hamilton Depression Rating Scale (HAMD)-17 items was used to evaluate the severity of symptoms of depression. A total score of more than 24 may indicate severe depressive symptoms; A score above 17 may be mild to moderate depressive; If the score is less than 7, the patient has no symptoms of depression. The higher the total score of the scale, the more severe the depressive symptoms.
measure: The change of scores in Hamilton Anxiety Rating Scale (HAMA) from baseline to Week 4.
time frame: baseline, Week 1, week 2, week 3, week 4
description: The aim is to explore whether tDCS add on SSRI or SNRI will alleviate the severity of anxious symptoms as measured with HAMA after 4 weeks of treatment, and investigators assess the scale at baseline and week 1, 2, 3, 4. Hamilton Anxiety Rating Scale (HAMA) was used to evaluate the severity of anxiety symptoms and the effects of intervention in patients with anxiety and depressive disorders. The total score ≥ 29 may be severe anxiety; ≥ 21, there may be obvious anxiety; ≥ 14, there may be anxiety; more than 7, there may be anxiety; if less than 7, there will be no anxiety symptoms.
measure: The change of scores in Pittsburgh Sleep Quality Index (PSQI) from basline to week 8.
time frame: baseline, Week 4, week8
description: The aim is to investigate whether active-stimuli in addition to regular treatment with an antidepressant will improve the sleep quality as measured with Pittsburgh Sleep Quality Index (PSQI) after 4 weeks of treatment compared to sham-stimuli, and investigators assess the scale at baseline and week 4,8. PSQI was used to evaluate the sleep quality of the subjects in the last month. The total score of PSQI ranged from 0 to 21. The higher the score, the worse the sleep quality.
measure: The change of scores in quality of life (QOL) from baseline to week 8.
time frame: baseline, Week 4, week 8
description: The aim is to investigate whether active-stimuli in addition to regular treatment with an antidepressant will improve the quality of life as measured with quality of life (QOL) after 4 weeks of treatment compared to sham-stimuli, and investigators assess the scale at baseline and week 4,8. The QOL scale evaluates the physical health, mental health, social relations and other aspects of the participants. The higher the score is, the better the quality of life is.
measure: The change of sores in suicidal risk assessment scale from baseline to week 8
time frame: baseline, Week 4, week 8
description: The aim is to investigate whether active-stimuli in addition to regular treatment with an antidepressant will reduce the risk suicide as measured with the suicidal risk assessment scale after 4 weeks of treatment compared to sham-stimuli, and investigators assess the scale at baseline and week 4,8. The higher the score of the suicidal risk assessment scale, the higher the risk of suicide.
measure: The change of scores in Repeatable Battery for the Assessment of neuropsychological Status (Rebans).
time frame: baseline, Week 4, week 8
description: The aim is to observe whether active-stimuli in addition to regular treatment with an antidepressant will improve the cognitive function as measured with Repeatable Battery for the Assessment of Neuropsychological Status (Rebans) after 4 weeks of treatment compared to sham-stimuli, and investigators assess the scale at baseline and week 4,8. The higher the score of the scale, the cognitive function is better.
measure: The changes of levels of biomarkers in peripheral blood from baseline to week 4
time frame: baseline, week 4
description: The aim is to investigate the change of cortisol level of saliva and intestinal flora as active stimuli in addition to regular treatment with an antidepressant after 4 weeks of treatment compared to sham stimuli, and investigators collect the specimens at baseline and week 4.
Saliva collection tube to collect saliva, collect naturally discharged saliva in a clean test tube (at least 2ml). Saliva was centrifuged under 1500rpm for 15 minutes and the filtrate was cryopreserved at-80 °C. the saliva was analyzed by ELISA kit.
Fecal collection: a) intercept the middle part of the sample with a sterile toothpick or fecal sampler (the surface of feces contains exfoliated cells of intestinal mucosa; the outside is easy to be contaminated, and some bacterial DNA begins to degrade after contact with air), take about the size of peanuts and put them into aseptic 2.0mL centrifuge tubes, 3-5 tubes for each sample are taken for backup，and then put into-80 °C cryopreservation after sub-packaging.
measure: Adverse events from baseline to week 4
time frame: week 1, week 2, week 3, week 4
description: The aim is to evaluate the adverse effects during the treatment.
arm group label: tDCS group
arm group type: Experimental
description: participants receive 20 min sessions of 2 mA direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 4 weeks combine a selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitors(SNRI)
arm group label: Sham group
arm group type: Sham Comparator
description: Participants receive sham stimulation that administered similarly, but with current turned off after 30s combine a selective serotonin reuptake inhibitor (SSRI) or a serotonin and norepinephrine reuptake inhibitors(SNRI)
intervention type: Device
intervention name: Transcranial Direct Current Stimulation (tDCS)-active
description: Transcranial direct current stimulation (TDC) is a non-invasive neuromodulation technique of the brain with a DC microelectrical stimulator, a cathode electrode and an anode electrode, and a control software to set the output of the stimulation type，participants receive 20 min sessions of 2 mA direct current delivered over the dorsolateral prefrontal cortex, 5 days per week, for 4 weeks
arm group label: tDCS group
other name: active
intervention type: Device
intervention name: Transcranial Direct Current Stimulation (tDCS)-sham
description: Transcranial direct current stimulation (TDC) is a non-invasive neuromodulation technique of the brain with a DC microelectrical stimulator, a cathode electrode and an anode electrode, and a control software to set the output of the stimulation type. Participants receive sham stimulation over the dorsolateral prefrontal cortex, with current turned off after 30 second. The session last 20 min 5 days per week, for 4 weeks
arm group label: Sham group
other name: sham
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Jie Li, Doctor
phone: 022-88188006
email: tjlijie3827@163.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
sharing ipd: Undecided