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/NCT05964062</url>
    </required_header>
    <id_info>
      <org_study_id>CPLOCDpreSMA</org_study_id>
      <nct_id>NCT05964062</nct_id>
    </id_info>
    <brief_title>pBFS Guided High-dose rTMS Therapy for Treatment-Resistant Obsessive-Compulsive Disorder</brief_title>
    <official_title>Personalized Brain Functional Sectors (pBFS) Guided High-dose rTMS Therapy for Treatment-resistant Obsessive-Compulsive 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>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The research aims to evaluate the safety and efficacy of pBFS-guided High-dose rTMS therapy&#xD;
        targeting preSMA for patients with treatment-resistant Obsessive-Compulsive Disorder.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In 2018, rTMS received approval from the U.S. Food and Drug Administration (FDA) for the&#xD;
        treatment of OCD. Based on a systematic meta-analysis of randomized clinical trials,&#xD;
        researchers compared the efficacy of different intervention targets (DMPFC, DLPFC, OFC, SMA)&#xD;
        and found that targeting the anterior part of the right SMA in patients yielded the best&#xD;
        response rates for individuals with obsessive-compulsive disorder (OCD) while targeting the&#xD;
        DLPFC showed poor efficacy. However, the preSMA is a large region, and different nodes within&#xD;
        this region have distinct functional connections with other areas. Thus, precise localization&#xD;
        of neural circuitry implicated in OCD symptomatology is essential for achieving effective&#xD;
        therapeutic interventions. Leveraging an innovative technique pBFS, the current study aims to&#xD;
        identify individual-specific preSMA targets with functional connectivity to the attention&#xD;
        network, enabling a more personalized and targeted approach to diagnosis and treatment for&#xD;
        OCD patients. A novel high-dose treatment modality known as SAINT received approval from the&#xD;
        U.S. FDA in September 2022 for managing the treatment-resistant major depressive disorder.&#xD;
        Building upon these findings, this study hypothesizes that high-dose iTBS targeting the&#xD;
        preSMA guided by pBFS will have a significant therapeutic effect on clinical symptoms in&#xD;
        treatment-resistant OCD patients.&#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 double-blind&#xD;
        manner in a 2:1 ratio to the active rTMS group, or sham-control group. Then all participants&#xD;
        will undergo a 5-day rTMS modulation and a 1-month, 2-month 3-month follow-up visit. Patients&#xD;
        will have a stable treatment regimen during the 5-day treatment and one-month post-treatment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">July 20, 2023</start_date>
    <completion_date type="Anticipated">October 20, 2024</completion_date>
    <primary_completion_date type="Anticipated">July 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>response rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)</measure>
      <time_frame>Baseline, Day 5, one-month post-treatment</time_frame>
      <description>The Y-BOCS is a validated instrument stratifying the severity of obsessive episodes. This validated questionnaire was used to assess the response rate and remission rate of obsessive episodes. This research compared the response rates of Y-BOCS between groups using non-parametric rank-sum tests to assess improvement immediately post-intervention. Response is defined as a symptom improvement ≥35% on these scales;</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>remission rate estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)</measure>
      <time_frame>Baseline, Day 5, one-month post-treatment, two-month post-treatment, three-month post-treatment</time_frame>
      <description>Remission was defined as a score &lt;8.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>partial response rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)</measure>
      <time_frame>Baseline, Day 5, one-month post-treatment,two-month post-treatment, three-month post-treatment</time_frame>
      <description>Partial response is defined as a symptom 35% ≥ improvement ≥25% on Y-BOCS;</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>cognitive change in Stroop</measure>
      <time_frame>Baseline, Day 5</time_frame>
      <description>The Stroop test can be used to measure a person's selective attention capacity and skills, processing speed, and alongside other tests to evaluate overall executive processing abilities.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>cognitive change in Hopkins verbal learning test(immediate recall)</measure>
      <time_frame>Baseline, Day 5</time_frame>
      <description>The Hopkins Verbal Learning Test (HVLT-R) is one such assessment that consists of memorization of a list of words to test the ability to recall immediately after memorization</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>cognitive change in Trail-Making Test</measure>
      <time_frame>Baseline, Day 5</time_frame>
      <description>The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Obsessive-Compulsive Disorder</condition>
    <condition>OCD</condition>
    <arm_group>
      <arm_group_label>active rTMS treatment</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>10 sessions of active rTMS would be delivered to the right preSMA daily, with a session of 1800 pulse.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>sham rTMS treatment</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>5 sessions of sham rTMS would be delivered to the right preSMA daily, with a session of 1800 pulse.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>active rTMS treatment</intervention_name>
      <description>Participants will receive 10 sessions per day of 1800 pulses per session, lasting for 5 days. Individualized targets will be generated using the pBFS method.</description>
      <arm_group_label>active rTMS treatment</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>sham rTMS treatment</intervention_name>
      <description>The parameters in the sham arms are the same as the active stimulation groups. Stimulation was delivered by the same device as the active group fitted with a sham coil.</description>
      <arm_group_label>sham rTMS treatment</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Hospitalized/outpatient patients aged 18-65 years (inclusive), male or female.&#xD;
  &#xD;
            -  Meet the diagnostic criteria of DSM-5(Diagnostic and Statistical Manual of Mental&#xD;
               Disorders, Fifth Edition) for obsessive-compulsive disorder, and currently&#xD;
               experiencing a first or recurrence episode.&#xD;
  &#xD;
            -  Total Y-BOCS score ≥20 and total HAMD score &lt;17 before randomization.&#xD;
  &#xD;
            -  Before randomization, patients must have received a minimum of 2 months of maintenance&#xD;
               treatment with SSRI medication prior to randomization, or have undergone maintenance&#xD;
               CBT treatment with inadequate response to SSRI medication (less than 50% symptom&#xD;
               improvement), or have previously shown inadequate response (less than 50% symptom&#xD;
               improvement) to at least one trial of SSRI medication or cognitive-behavioral therapy.&#xD;
               Patients currently taking medication should have been on a stable dose for 8 weeks.&#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;
            -  Does not meet the inclusion criteria&#xD;
  &#xD;
            -  Exhibiting hoarding disorder.&#xD;
  &#xD;
            -  Meet DSM-5 diagnostic criteria for other mental disorders (such as schizophrenia,&#xD;
               schizoaffective disorder, post-traumatic stress disorder, bipolar disorder, and&#xD;
               secondary depression, 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, light therapy within 3 months;&#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;
            -  Patients with serious or unstable diseases of the cardiovascular, liver, kidney,&#xD;
               blood, endocrine, neurological system, and other systems or organs.&#xD;
  &#xD;
            -  Female of childbearing potential who plans to become pregnant during the trial. Female&#xD;
               that is pregnant or breastfeeding.&#xD;
  &#xD;
            -  Substance abuse or dependence (including alcohol misuse and drugs) within the past 6&#xD;
               months.&#xD;
  &#xD;
            -  First-degree relatives have bipolar affective disorder and schizophrenia.&#xD;
  &#xD;
            -  There is a significant risk of suicide (MADRS item 3 ≥ 3).&#xD;
  &#xD;
            -  Difficulty or inability to engage in normal communication, understand or follow&#xD;
               instructions, and cooperate with treatment and evaluators.&#xD;
  &#xD;
            -  Patients currently in any clinical trials of other drugs or physical therapy ( DBS,&#xD;
               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, Ph.D.</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>July 2023</verification_date>
    <study_first_submitted>July 11, 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>Obsessive-Compulsive Disorder</keyword>
    <keyword>Treatment-resistant OCD</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Compulsive Personality Disorder</mesh_term>
      <mesh_term>Obsessive-Compulsive Disorder</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/NCT05964062
  org study id: CPLOCDpreSMA
  nct id: NCT05964062
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The research aims to evaluate the safety and efficacy of pBFS-guided High-dose rTMS therapy
        targeting preSMA for patients with treatment-resistant Obsessive-Compulsive Disorder.
  In 2018, rTMS received approval from the U.S. Food and Drug Administration (FDA) for the
        treatment of OCD. Based on a systematic meta-analysis of randomized clinical trials,
        researchers compared the efficacy of different intervention targets (DMPFC, DLPFC, OFC, SMA)
        and found that targeting the anterior part of the right SMA in patients yielded the best
        response rates for individuals with obsessive-compulsive disorder (OCD) while targeting the
        DLPFC showed poor efficacy. However, the preSMA is a large region, and different nodes within
        this region have distinct functional connections with other areas. Thus, precise localization
        of neural circuitry implicated in OCD symptomatology is essential for achieving effective
        therapeutic interventions. Leveraging an innovative technique pBFS, the current study aims to
        identify individual-specific preSMA targets with functional connectivity to the attention
        network, enabling a more personalized and targeted approach to diagnosis and treatment for
        OCD patients. A novel high-dose treatment modality known as SAINT received approval from the
        U.S. FDA in September 2022 for managing the treatment-resistant major depressive disorder.
        Building upon these findings, this study hypothesizes that high-dose iTBS targeting the
        preSMA guided by pBFS will have a significant therapeutic effect on clinical symptoms in
        treatment-resistant OCD patients.
  
        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 double-blind
        manner in a 2:1 ratio to the active rTMS group, or sham-control group. Then all participants
        will undergo a 5-day rTMS modulation and a 1-month, 2-month 3-month follow-up visit. Patients
        will have a stable treatment regimen during the 5-day treatment and one-month post-treatment.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: response rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
  time frame: Baseline, Day 5, one-month post-treatment
  description: The Y-BOCS is a validated instrument stratifying the severity of obsessive episodes. This validated questionnaire was used to assess the response rate and remission rate of obsessive episodes. This research compared the response rates of Y-BOCS between groups using non-parametric rank-sum tests to assess improvement immediately post-intervention. Response is defined as a symptom improvement ≥35% on these scales;
  measure: remission rate estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
  time frame: Baseline, Day 5, one-month post-treatment, two-month post-treatment, three-month post-treatment
  description: Remission was defined as a score <8.
  measure: partial response rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
  time frame: Baseline, Day 5, one-month post-treatment,two-month post-treatment, three-month post-treatment
  description: Partial response is defined as a symptom 35% ≥ improvement ≥25% on Y-BOCS;
  measure: cognitive change in Stroop
  time frame: Baseline, Day 5
  description: The Stroop test can be used to measure a person's selective attention capacity and skills, processing speed, and alongside other tests to evaluate overall executive processing abilities.
  measure: cognitive change in Hopkins verbal learning test(immediate recall)
  time frame: Baseline, Day 5
  description: The Hopkins Verbal Learning Test (HVLT-R) is one such assessment that consists of memorization of a list of words to test the ability to recall immediately after memorization
  measure: cognitive change in Trail-Making Test
  time frame: Baseline, Day 5
  description: The test can provide information about visual search speed, scanning, speed of processing, mental flexibility, and executive functioning
  arm group label: active rTMS treatment
  arm group type: Experimental
  description: 10 sessions of active rTMS would be delivered to the right preSMA daily, with a session of 1800 pulse.
  arm group label: sham rTMS treatment
  arm group type: Sham Comparator
  description: 5 sessions of sham rTMS would be delivered to the right preSMA daily, with a session of 1800 pulse.
  intervention type: Device
  intervention name: active rTMS treatment
  description: Participants will receive 10 sessions per day of 1800 pulses per session, lasting for 5 days. Individualized targets will be generated using the pBFS method.
  arm group label: active rTMS treatment
  intervention type: Device
  intervention name: sham rTMS treatment
  description: The parameters in the sham arms are the same as the active stimulation groups. Stimulation was delivered by the same device as the active group fitted with a sham coil.
  arm group label: sham rTMS treatment
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Hesheng Liu, Ph.D.
  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: Compulsive Personality Disorder
  mesh term: Obsessive-Compulsive Disorder