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/NCT05976009</url>
    </required_header>
    <id_info>
      <org_study_id>CPLMDDdiffTargXY</org_study_id>
      <nct_id>NCT05976009</nct_id>
    </id_info>
    <brief_title>pBFS-Guided rTMS Therapy Over Different Targets for Treatment-Resistant Depression</brief_title>
    <official_title>Personalized Brain Functional Sector-guided rTMS Therapy Over Different Targets for Treatment-resistant Depression</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Changping Laboratory</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Changping Laboratory</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To explore the effectiveness and safety of rTMS intervention with different targets in the&#xD;
        left prefrontal cortex defined using the pBFS method, in adult patients with moderate and&#xD;
        severe depressive disorder. Second, investigate the neural circuit that responds to the rTMS&#xD;
        intervention using individualized brain image analysis, which may help to establish an&#xD;
        effective target for the neuromodulation of patients with major depressive disorder.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Stimulation of the dorsolateral prefrontal cortex(DLPFC) and ventromedial prefrontal cortex&#xD;
        (DMPFC) as target sites for rTMS intervention in depressive disorders has shown some&#xD;
        therapeutic efficacy. However, overall patient response rates remain suboptimal, partly&#xD;
        because the prefrontal cortex is a large region encompassing multiple functional networks.&#xD;
        Analyses suggest that targeting different targets within the dorsolateral and ventromedial&#xD;
        prefrontal cortex for intervention in depressive disorder patients may activate distinct&#xD;
        functional networks. Therefore, selecting appropriate targets within the prefrontal cortex&#xD;
        that accurately modulate the functional networks involved in depressive disorder patients is&#xD;
        crucial for achieving effective clinical outcomes. Fox et al. have demonstrated that clinical&#xD;
        response and individualized target sites in the dorsolateral prefrontal cortex are associated&#xD;
        with functional connectivity to the subgenual cingulate cortex (sgACC). However, some&#xD;
        analyses have indicated that rTMS target sites based solely on minimal sgACC connectivity may&#xD;
        not be optimal for all depressive symptoms. Therefore, identifying individualized stimulation&#xD;
        targets that improve core symptoms in depressed patients is important for achieving more&#xD;
        effective personalized treatment of depressive disorders. This study aims to explore the&#xD;
        efficacy and safety of rTMS interventions targeting 40 prefrontal cortex sites in depressive&#xD;
        disorder patients and functional imaging-based mechanisms for optimal stimulation targets.&#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 assigned a random intervention&#xD;
        target from 40 prefrontal cortex sites. Then all participants will undergo a 14-day rTMS&#xD;
        modulation and a week follow-up visit. Participants will keep a stable treatment regime&#xD;
        during treatment and follow-up.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 15, 2023</start_date>
    <completion_date type="Anticipated">September 20, 2024</completion_date>
    <primary_completion_date type="Anticipated">August 15, 2024</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>change in MADRS</measure>
      <time_frame>Baseline and Day 14(immediate 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>
    </primary_outcome>
    <secondary_outcome>
      <measure>change in MADRS</measure>
      <time_frame>Baseline, Day 7, Day 14, Day 21</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 HAMD</measure>
      <time_frame>Baseline, Day 7, Day 14, Day 21</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>cognitive change in Digit Symbol Substitution Test (DSST)</measure>
      <time_frame>Baseline, Day 21 (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 21 (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 21 (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 21 (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>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Major Depressive Disorder</condition>
    <condition>Treatment Resistant Depression</condition>
    <condition>MDD</condition>
    <arm_group>
      <arm_group_label>active rTMS treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>2 sessions with 1800 pulses per session and 50min inter-session interval of active rTMS will deliver to the assigned target</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>active rTMS stimulating</intervention_name>
      <description>Two sessions of active rTMS would be delivered, with 1800 pulse/session and 50 min inter-session intervals.</description>
      <arm_group_label>active rTMS treatment</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Meet the diagnostic criteria of DSM-5(Diagnostic and Statistical Manual of Mental&#xD;
               Disorders, Fifth Edition) for depression disorder without psychotic symptoms, and&#xD;
               currently experiencing a recurrence episode.&#xD;
  &#xD;
            -  Total HAMD17 score ≥20 and total MADRS score ≥20 before randomization.&#xD;
  &#xD;
            -  Hospitalized/outpatient patients aged 18-65 years (inclusive), male or female.&#xD;
  &#xD;
            -  Inadequate response to at least one antidepressant trial of adequate doses and&#xD;
               duration.&#xD;
  &#xD;
            -  A stable antidepressant regimen for at least 4 weeks at a dose not lower than the&#xD;
               prescribed range of drug use before randomization.&#xD;
  &#xD;
            -  The Maudsley Staging Method (MSM) is used to assess patients as having at least a&#xD;
               moderate level of treatment-resistant condition (MSM score ≥ 7 points).&#xD;
  &#xD;
            -  Voluntarily participate in the trial and sign informed consent. Able to comply with&#xD;
               the planned visit, examination and treatment plan, and other study procedures.&#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;
            -  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, and light therapy within 3 months;&#xD;
  &#xD;
            -  Patients with serious heart, liver, kidney diseases, diabetes and other serious&#xD;
               physical diseases, causing symptoms and signs of brain abnormalities, or body failure;&#xD;
  &#xD;
            -  Patients with organic brain diseases (such as ischemic stroke, cerebral hemorrhage,&#xD;
               brain tumor, etc.) and a history of severe brain trauma as judged by the researcher;&#xD;
  &#xD;
            -  Female of childbearing potential who plans to become pregnant during the trial.&#xD;
  &#xD;
            -  Female that is pregnant or breastfeeding.&#xD;
  &#xD;
            -  Substance abuse or dependence (including alcohol, drugs, and other psychoactive&#xD;
               substances) in the past 1 year;&#xD;
  &#xD;
            -  First-degree relatives have bipolar affective disorder.&#xD;
  &#xD;
            -  There is a significant risk of suicide (MADRS item 10 ≥ 5).&#xD;
  &#xD;
            -  Difficulty or inability to engage in normal communication, understand or follow&#xD;
               instructions, and cooperate with treatment and evaluators.&#xD;
  &#xD;
            -  Currently participating in clinical trials of other drugs or physical therapy (e.g.&#xD;
               deep brain stimulation (DBS), electroconvulsive therapy (ECT), rTMS).&#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, Ph.D.</last_name>
      <phone>010-80726688</phone>
      <email>meilingli@cpl.ac.cn</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 3, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>MDD</keyword>
    <keyword>Major Depressive Disorder</keyword>
    <keyword>Treatment Resistant Depression</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>
      <mesh_term>Depressive Disorder, Treatment-Resistant</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/NCT05976009
  org study id: CPLMDDdiffTargXY
  nct id: NCT05976009
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  To explore the effectiveness and safety of rTMS intervention with different targets in the
        left prefrontal cortex defined using the pBFS method, in adult patients with moderate and
        severe depressive disorder. Second, investigate the neural circuit that responds to the rTMS
        intervention using individualized brain image analysis, which may help to establish an
        effective target for the neuromodulation of patients with major depressive disorder.
  Stimulation of the dorsolateral prefrontal cortex(DLPFC) and ventromedial prefrontal cortex
        (DMPFC) as target sites for rTMS intervention in depressive disorders has shown some
        therapeutic efficacy. However, overall patient response rates remain suboptimal, partly
        because the prefrontal cortex is a large region encompassing multiple functional networks.
        Analyses suggest that targeting different targets within the dorsolateral and ventromedial
        prefrontal cortex for intervention in depressive disorder patients may activate distinct
        functional networks. Therefore, selecting appropriate targets within the prefrontal cortex
        that accurately modulate the functional networks involved in depressive disorder patients is
        crucial for achieving effective clinical outcomes. Fox et al. have demonstrated that clinical
        response and individualized target sites in the dorsolateral prefrontal cortex are associated
        with functional connectivity to the subgenual cingulate cortex (sgACC). However, some
        analyses have indicated that rTMS target sites based solely on minimal sgACC connectivity may
        not be optimal for all depressive symptoms. Therefore, identifying individualized stimulation
        targets that improve core symptoms in depressed patients is important for achieving more
        effective personalized treatment of depressive disorders. This study aims to explore the
        efficacy and safety of rTMS interventions targeting 40 prefrontal cortex sites in depressive
        disorder patients and functional imaging-based mechanisms for optimal stimulation targets.
  
        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 assigned a random intervention
        target from 40 prefrontal cortex sites. Then all participants will undergo a 14-day rTMS
        modulation and a week follow-up visit. Participants will keep a stable treatment regime
        during treatment and follow-up.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: change in MADRS
  time frame: Baseline and Day 14(immediate 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 MADRS
  time frame: Baseline, Day 7, Day 14, Day 21
  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 HAMD
  time frame: Baseline, Day 7, Day 14, Day 21
  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: cognitive change in Digit Symbol Substitution Test (DSST)
  time frame: Baseline, Day 21 (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 21 (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 21 (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 21 (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
  arm group label: active rTMS treatment
  arm group type: Experimental
  description: 2 sessions with 1800 pulses per session and 50min inter-session interval of active rTMS will deliver to the assigned target
  intervention type: Device
  intervention name: active rTMS stimulating
  description: Two sessions of active rTMS would be delivered, with 1800 pulse/session and 50 min inter-session intervals.
  arm group label: active rTMS treatment
  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, Ph.D.
  phone: 010-80726688
  email: meilingli@cpl.ac.cn
  responsible party type: Sponsor
  mesh term: Depression
  mesh term: Depressive Disorder
  mesh term: Depressive Disorder, Major
  mesh term: Depressive Disorder, Treatment-Resistant