xml: <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/NCT05964036</url>
    </required_header>
    <id_info>
      <org_study_id>CPLMDDHidoseDM</org_study_id>
      <nct_id>NCT05964036</nct_id>
    </id_info>
    <brief_title>pBFS-guided High-dose TMS Over DMPFC for Treatment-resistant Major Depressive Disorder</brief_title>
    <official_title>Personalized Brain Functional Sectors (pBFS)-Guided DMPFC With High-dose rTMS for Treatment-resistant Depressive Disorder: a Randomized, Double-blind, Sham-controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Changping Laboratory</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Changping Laboratory</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 investigators aim to evaluate the safety and efficacy of pBFS-guided DMPFC target and&#xD;
        high-dose rTMS therapy for the treatment of patients with treatment-resistant depression&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for&#xD;
        treatment-resistant depression. Currently, the FDA cleared the SAINT Neuromodulation System&#xD;
        for the treatment of Treatment-Resistant Depression(TRD) over the left dorsolateral&#xD;
        prefrontal cortex (DLPFC). This methodology has been effective in a short period of time for&#xD;
        treatment-resistant depression. However, some patients may not be able to persist in&#xD;
        completing the treatment because they cannot bear the pain during treatment. The dorsomedial&#xD;
        prefrontal cortex (DMPFC) region is relatively posterior, and DMPFC as an intervention target&#xD;
        has been proven to have antidepressant effects, and patients have better pain tolerance&#xD;
        during treatment, which can be used as an alternative to DLPFC target, so it is urgent to&#xD;
        explore the effectiveness and safety of high-dose iTBS targeting DMPFC in the treatment of&#xD;
        depression.&#xD;
  &#xD;
        After being informed about the study and potential risks. All patients giving written&#xD;
        informed consent will undergo a screening period to determine eligibility for study entry. At&#xD;
        week 0, patients who meet the eligibility requirements will be randomized in a blind manner&#xD;
        in a 2:1 ratio to the active-rTMS group, and sham-rTMS group. Then all participants will&#xD;
        undergo a 5-day rTMS modulation followed by two-week and four-week follow-up visits.&#xD;
        Participants will keep a stable treatment regime during treatment and the four-week&#xD;
        follow-up.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">July 20, 2023</start_date>
    <completion_date type="Anticipated">July 20, 2024</completion_date>
    <primary_completion_date type="Anticipated">April 20, 2024</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>change in Montgomery-Asberg Depression Rating Scale (MADRS)</measure>
      <time_frame>Baseline, Day 5</time_frame>
      <description>The MADRS is a validated instrument stratifying the severity of depressive episodes in adults. The MADRS has an overall score ranging from 0 (no depression) to 60 (worst depression).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in MADRS</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment</time_frame>
      <description>A provider-administered questionnaire was used to assess remission and recovery from depression. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The MADRS has an overall score range from 0-60, with higher scores corresponding to higher levels of depression</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Hamilton Depression Scale (HAMD-17)</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment</time_frame>
      <description>A provider-administered questionnaire was used to assess remission and recovery from depression. The Hamilton Depression Rating Scale (HAMD) is the most widely used clinician-administered depression assessment scale. The Ham-17 version consists of 17 items assessing mood, guilt, general somatic symptoms, work and activities, anxiety, and slowness of thought and speech. Each item is scored on a scale of 0 to 4, except for the somatic, sleep, and insight items which are scored 0 to 2. On the HAMD-17 there can be a total score of 52. Higher scores represent higher depression severity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Quick Inventory of Depressive Symptomatology Self-Report (QIDS_SR)</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment</time_frame>
      <description>A provider-administered questionnaire was used to assess remission and recovery from depression. The 16-item QIDS_SR is a widely used self-report instrument covering depressive symptoms incorporating nine Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) diagnostic criteria for major depressive disorders. Each item is scored on a scale of 0 to 4. Higher scores represent higher depression severity.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>cognitive change in Digit Symbol Substitution Test (DSST)</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment)</time_frame>
      <description>Cognitive scores are measured using Chinese brief cognitive test (C-BCT), the DSST equires a subject to match symbols to numbers according to a key located on the top of the page</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>cognitive change in continuous performance test (CPT)</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment)</time_frame>
      <description>CPT from the C-BCT measures a person's sustained and selective attention</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>cognitive change in Trail-Making Test (TMT)</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment)</time_frame>
      <description>The TMT test from the C-BCT can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>cognitive change in Digit Span Test (DST)</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment)</time_frame>
      <description>DST from the C-BCT is a measure of verbal short term and working memory that can be used in two formats, Forward Digit Span and Reverse Digit Span</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety estimated using SSI</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment</time_frame>
      <description>Scale for Suicide Ideation (SSI) measures suicide ideation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety estimated using YMRS</measure>
      <time_frame>Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment</time_frame>
      <description>Young Mania Rating Scale(YMARS) measures mania</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">45</enrollment>
    <condition>Depression</condition>
    <condition>Major Depressive Disorder</condition>
    <condition>Severe Depression</condition>
    <arm_group>
      <arm_group_label>active TMS</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>active iTBS coupled with medical therapy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>sham TMS</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>Sham iTBS coupled with medical therapy</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>active TMS</intervention_name>
      <description>Participants will receive 10 sessions per day of 1800 pulses per session, lasting for 5 days. Individualized target in the DMPFC will be generated using the pBFS method</description>
      <arm_group_label>active TMS</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>sham TMS</intervention_name>
      <description>The parameters in the sham arm are the same as in the active stimulation group. Stimulation was delivered by the same device as the active group fitted with a sham coil</description>
      <arm_group_label>sham TMS</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  DSM-5 diagnosis of depressive disorder, recurrent episodes;&#xD;
  &#xD;
            -  A total score of at least 20 on the HAMD-17 and Montgomery-Asberg Depression Rating&#xD;
               Scale;&#xD;
  &#xD;
            -  Aged 18-65 years, female or male;&#xD;
  &#xD;
            -  Inadequate response to at least one antidepressant trial of adequate doses and&#xD;
               duration;&#xD;
  &#xD;
            -  The MSM (Maudsley Staging Method) score ≥ 7;&#xD;
  &#xD;
            -  Stable antidepressant regimen for at least 4 weeks before treatment;&#xD;
  &#xD;
            -  Understand the trial and sign the informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Meet DSM-5 diagnostic criteria for other mental disorders (such as schizophrenia&#xD;
               spectrum disorders, bipolar and related disorders, neurodevelopmental disorders,&#xD;
               neurocognitive disorders, or depressive disorders due to substances and/or&#xD;
               medications, depressive disorders due to other medical problems, etc.);&#xD;
  &#xD;
            -  Patients with a cardiac pacemaker, cochlear implant, or other metal foreign body and&#xD;
               any electronic equipment implanted in the body, patients with claustrophobia and other&#xD;
               contraindications to magnetic resonance scanning, and patients with contraindications&#xD;
               to rTMS treatment;&#xD;
  &#xD;
            -  Patients with serious or unstable diseases of the cardiovascular, liver, kidney,&#xD;
               blood, endocrine, neurological system, and other systems or organs, especially those&#xD;
               with organic brain diseases (such as ischemic stroke, cerebral hemorrhage, brain&#xD;
               tumor, etc.) and a history of severe brain trauma as judged by the researcher;&#xD;
  &#xD;
            -  History of epilepsy (presence of at least 2 uninduced seizures more than 24 hours&#xD;
               apart, or diagnosis of the epileptic syndrome, or seizures within the past 12 months);&#xD;
               Or currently received medications or other treatments that will lower the seizure&#xD;
               threshold;&#xD;
  &#xD;
            -  History of ECT, rTMS, VNS, DBS, tDCS, light therapy, or other physical therapy related&#xD;
               to mental illness within 3 months;&#xD;
  &#xD;
            -  Currently receiving or planning to start formal cognitive or behavioral therapy, or&#xD;
               systemic psychological therapy (interpersonal therapy, dynamic therapy, cognitive&#xD;
               behavioral therapy, etc.) during the trial.&#xD;
  &#xD;
            -  Substance abuse or dependence (including alcohol, drugs, and other psychoactive&#xD;
               substances) in the past 1 year;&#xD;
  &#xD;
            -  The female of childbearing potential who plans to become pregnant during the trial,&#xD;
               and that is pregnant or breastfeeding.&#xD;
  &#xD;
            -  Patients in any clinical trials of other drugs or physical therapy within 1 month&#xD;
               before the screening.&#xD;
  &#xD;
            -  First-degree relatives have bipolar affective disorder.&#xD;
  &#xD;
            -  Difficulty or inability to engage in normal communication, understand or follow&#xD;
               instructions, and cooperate with treatment and evaluators.&#xD;
  &#xD;
            -  Investigators think that was inappropriate to participate.&#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_official>
      <last_name>hesheng Liu</last_name>
      <role>Study Chair</role>
      <affiliation>Changping Laboratory</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Meiling Li, phd</last_name>
      <phone>13540014981</phone>
      <phone_ext>86</phone_ext>
      <email>limeilingcheng@163.com</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 12, 2023</study_first_submitted>
    <study_first_submitted_qc>July 19, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 19, 2023</last_update_submitted>
    <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>transcranial magnetic stimulation, rTMS</keyword>
    <keyword>DMPFC</keyword>
    <keyword>pBFS</keyword>
    <keyword>precision target</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>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05964036
  org study id: CPLMDDHidoseDM
  nct id: NCT05964036
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The investigators aim to evaluate the safety and efficacy of pBFS-guided DMPFC target and
        high-dose rTMS therapy for the treatment of patients with treatment-resistant depression
  Repetitive transcranial magnetic stimulation (rTMS) is an established therapy for
        treatment-resistant depression. Currently, the FDA cleared the SAINT Neuromodulation System
        for the treatment of Treatment-Resistant Depression(TRD) over the left dorsolateral
        prefrontal cortex (DLPFC). This methodology has been effective in a short period of time for
        treatment-resistant depression. However, some patients may not be able to persist in
        completing the treatment because they cannot bear the pain during treatment. The dorsomedial
        prefrontal cortex (DMPFC) region is relatively posterior, and DMPFC as an intervention target
        has been proven to have antidepressant effects, and patients have better pain tolerance
        during treatment, which can be used as an alternative to DLPFC target, so it is urgent to
        explore the effectiveness and safety of high-dose iTBS targeting DMPFC in the treatment of
        depression.
  
        After being informed about the study and potential risks. All patients giving written
        informed consent will undergo a screening period to determine eligibility for study entry. At
        week 0, patients who meet the eligibility requirements will be randomized in a blind manner
        in a 2:1 ratio to the active-rTMS group, and sham-rTMS group. Then all participants will
        undergo a 5-day rTMS modulation followed by two-week and four-week follow-up visits.
        Participants will keep a stable treatment regime during treatment and the four-week
        follow-up.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: change in Montgomery-Asberg Depression Rating Scale (MADRS)
  time frame: Baseline, Day 5
  description: The MADRS is a validated instrument stratifying the severity of depressive episodes in adults. The MADRS has an overall score ranging from 0 (no depression) to 60 (worst depression).
  measure: Change in MADRS
  time frame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
  description: A provider-administered questionnaire was used to assess remission and recovery from depression. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. The MADRS has an overall score range from 0-60, with higher scores corresponding to higher levels of depression
  measure: Change in Hamilton Depression Scale (HAMD-17)
  time frame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
  description: A provider-administered questionnaire was used to assess remission and recovery from depression. The Hamilton Depression Rating Scale (HAMD) is the most widely used clinician-administered depression assessment scale. The Ham-17 version consists of 17 items assessing mood, guilt, general somatic symptoms, work and activities, anxiety, and slowness of thought and speech. Each item is scored on a scale of 0 to 4, except for the somatic, sleep, and insight items which are scored 0 to 2. On the HAMD-17 there can be a total score of 52. Higher scores represent higher depression severity.
  measure: Change in Quick Inventory of Depressive Symptomatology Self-Report (QIDS_SR)
  time frame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
  description: A provider-administered questionnaire was used to assess remission and recovery from depression. The 16-item QIDS_SR is a widely used self-report instrument covering depressive symptoms incorporating nine Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) diagnostic criteria for major depressive disorders. Each item is scored on a scale of 0 to 4. Higher scores represent higher depression severity.
  measure: cognitive change in Digit Symbol Substitution Test (DSST)
  time frame: Baseline, Day 5 (Immediate Post-treatment)
  description: Cognitive scores are measured using Chinese brief cognitive test (C-BCT), the DSST equires a subject to match symbols to numbers according to a key located on the top of the page
  measure: cognitive change in continuous performance test (CPT)
  time frame: Baseline, Day 5 (Immediate Post-treatment)
  description: CPT from the C-BCT measures a person's sustained and selective attention
  measure: cognitive change in Trail-Making Test (TMT)
  time frame: Baseline, Day 5 (Immediate Post-treatment)
  description: The TMT test from the C-BCT can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning
  measure: cognitive change in Digit Span Test (DST)
  time frame: Baseline, Day 5 (Immediate Post-treatment)
  description: DST from the C-BCT is a measure of verbal short term and working memory that can be used in two formats, Forward Digit Span and Reverse Digit Span
  measure: Safety estimated using SSI
  time frame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
  description: Scale for Suicide Ideation (SSI) measures suicide ideation
  measure: Safety estimated using YMRS
  time frame: Baseline, Day 5 (Immediate Post-treatment), 14 days Post-treatment, 28 days Post-treatment
  description: Young Mania Rating Scale(YMARS) measures mania
  arm group label: active TMS
  arm group type: Experimental
  description: active iTBS coupled with medical therapy
  arm group label: sham TMS
  arm group type: Sham Comparator
  description: Sham iTBS coupled with medical therapy
  intervention type: Device
  intervention name: active TMS
  description: Participants will receive 10 sessions per day of 1800 pulses per session, lasting for 5 days. Individualized target in the DMPFC will be generated using the pBFS method
  arm group label: active TMS
  intervention type: Device
  intervention name: sham TMS
  description: The parameters in the sham arm are the same as in the active stimulation group. Stimulation was delivered by the same device as the active group fitted with a sham coil
  arm group label: sham TMS
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: hesheng Liu
  role: Study Chair
  affiliation: Changping Laboratory
  last name: Meiling Li, phd
  phone: 13540014981
  phone ext: 86
  email: limeilingcheng@163.com
  responsible party type: Sponsor
  mesh term: Depression
  mesh term: Depressive Disorder
  mesh term: Depressive Disorder, Major