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/NCT05964049</url>
    </required_header>
    <id_info>
      <org_study_id>CPLOCDDLPFC</org_study_id>
      <nct_id>NCT05964049</nct_id>
    </id_info>
    <brief_title>pBFS Guided rTMS Therapy for Treatment-resistant Obsessive-Compulsive Disorder</brief_title>
    <official_title>Personalized Brain Functional Sectors (pBFS) Guided 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 investigators aim to evaluate the safety and efficacy of pBFS-guided rTMS therapy&#xD;
        targeting DLPFC 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 randomized clinical trials, researchers have observed significant&#xD;
        variations in the intervention effects when targeting the dorsolateral prefrontal cortex&#xD;
        (DLPFC), which is a large region with different subregions and functional connections to&#xD;
        other areas across multiple functional networks. Precise targeting of neural circuitry&#xD;
        related to OCD symptoms is crucial for effective intervention. The ventrolateral prefrontal&#xD;
        cortex and insula are key components of the OCD functional circuitry within the ventral&#xD;
        attention/salience network. However, stimulating these brain regions with TMS is challenging,&#xD;
        and patients often have a low tolerance. Previous studies have found that effective targets&#xD;
        for various interventions used in psychiatric disorders are located within the same&#xD;
        functional circuitry. Therefore, in this study, The investigator employed the pBFS technique&#xD;
        to precisely locate the DLPFC subregions within the ventral attention/salience network. The&#xD;
        investigator hypothesizes that rTMS intervention targeting the DLPFC guided by pBFS will&#xD;
        significantly alleviate clinical symptoms in 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 15-day （3 weeks， treatment on weekdays） rTMS modulation. After treatment, 15-,&#xD;
        30-, 60-, and 90-day follow-up visits will occur. Participants will keep a stable treatment&#xD;
        regimen during the intervention and the first-month follow-up.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 16, 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 15(immediate post-treatment), 15- and 30-day 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. The response is defined as a symptom improvement of ≥35% on Y-BOCS;</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>remission rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)</measure>
      <time_frame>Baseline, Day 15(immediate post-treatment), 15- and 30-day 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 15(immediate post-treatment), 15- and 30-day 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 15(immediate post-treatment)</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 15(immediate post-treatment)</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 15(immediate post-treatment)</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>5 sessions of active rTMS would be delivered to the left DMPFC daily, with a session of 1800 pulse and inter-session interval of 20 min.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>sham control</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>5 sessions of sham rTMS would be delivered to the left DMPFC daily, with a session of 1800 pulse and inter-session interval of 20 min.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>active rTMS treatment</intervention_name>
      <description>Participants will receive 5 sessions per day of 1800 pulses per session, lasting for 15 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 control</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;
            -  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, drugs, and other psychoactive&#xD;
               substances) in the past 6 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 in any clinical trials of other drugs or physical therapy ( DBS, ECT, rTMS)&#xD;
               within 1 month before the screening&#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>
    <location>
      <facility>
        <name>Peking University Six Hospital</name>
        <address>
          <city>Beijing</city>
          <state>Beijing</state>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jinmin Liao</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 10, 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>OCD</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/NCT05964049
  org study id: CPLOCDDLPFC
  nct id: NCT05964049
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The investigators aim to evaluate the safety and efficacy of pBFS-guided rTMS therapy
        targeting DLPFC 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 randomized clinical trials, researchers have observed significant
        variations in the intervention effects when targeting the dorsolateral prefrontal cortex
        (DLPFC), which is a large region with different subregions and functional connections to
        other areas across multiple functional networks. Precise targeting of neural circuitry
        related to OCD symptoms is crucial for effective intervention. The ventrolateral prefrontal
        cortex and insula are key components of the OCD functional circuitry within the ventral
        attention/salience network. However, stimulating these brain regions with TMS is challenging,
        and patients often have a low tolerance. Previous studies have found that effective targets
        for various interventions used in psychiatric disorders are located within the same
        functional circuitry. Therefore, in this study, The investigator employed the pBFS technique
        to precisely locate the DLPFC subregions within the ventral attention/salience network. The
        investigator hypothesizes that rTMS intervention targeting the DLPFC guided by pBFS will
        significantly alleviate 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 15-day （3 weeks， treatment on weekdays） rTMS modulation. After treatment, 15-,
        30-, 60-, and 90-day follow-up visits will occur. Participants will keep a stable treatment
        regimen during the intervention and the first-month follow-up.
  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 15(immediate post-treatment), 15- and 30-day 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. The response is defined as a symptom improvement of ≥35% on Y-BOCS;
  measure: remission rates estimated using Yale-Brown Obsessive Compulsive Scale (Y-BOCS)
  time frame: Baseline, Day 15(immediate post-treatment), 15- and 30-day 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 15(immediate post-treatment), 15- and 30-day 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 15(immediate post-treatment)
  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 15(immediate post-treatment)
  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 15(immediate post-treatment)
  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: 5 sessions of active rTMS would be delivered to the left DMPFC daily, with a session of 1800 pulse and inter-session interval of 20 min.
  arm group label: sham control
  arm group type: Sham Comparator
  description: 5 sessions of sham rTMS would be delivered to the left DMPFC daily, with a session of 1800 pulse and inter-session interval of 20 min.
  intervention type: Device
  intervention name: active rTMS treatment
  description: Participants will receive 5 sessions per day of 1800 pulses per session, lasting for 15 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 control
  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
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Compulsive Personality Disorder
  mesh term: Obsessive-Compulsive Disorder