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/NCT06002581</url>
    </required_header>
    <id_info>
      <org_study_id>CCTR-2022B05</org_study_id>
      <nct_id>NCT06002581</nct_id>
    </id_info>
    <brief_title>Repetitive Transcranial Magnetic Stimulation(rTMS) Regulating Slow-wave to Delay the Progression of Parkinson's Disease</brief_title>
    <official_title>Clinical Study on the Efficacy and Safety of rTMS Regulating Slow-wave Sleep to Delay the Progression of Parkinson's Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</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>
        At present, no drug therapy has been proven to delay the progression of Parkinson's disease&#xD;
        (PD). rTMS, as a non-invasive neuromodulation method, can regulate Slow-wave sleep (SWS). SWS&#xD;
        is recognized closely related to neurodegeneration. However, there has been no clinical&#xD;
        studies on if rTMS could delay the progression of PD by regulating SWS.&#xD;
  &#xD;
        The main purpose of this study is to explore the changes of SWS in non-rapid eye movement&#xD;
        (NREM) sleep period in PD patients by using rTMS, and the relationship with potential&#xD;
        improvements of SWS and motor symptom delay. The study aims to find a potential new treatment&#xD;
        strategy to delay the neurodegenerative process in PD patients by modulating SWS by rTMS.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 29, 2023</start_date>
    <completion_date type="Anticipated">July 28, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 28, 2026</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>Double (Participant, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change of Motor Function in PD by Low Frequency rTMS Stimulation</measure>
      <time_frame>Day14</time_frame>
      <description>the score of Unified Parkinson's Disease Rating ScaleⅢ (UPDRSIII)[off] The higher the score, the more severe the motor dysfunction</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Effects of low-frequency rTMS stimulation on motor symptoms</measure>
      <time_frame>Day28,Day56</time_frame>
      <description>the score of Unified Parkinson's Disease Rating ScaleⅢ (UPDRSIII) [on] The higher the score, the more severe the motor dysfunction</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Measurement of improved balance function in patients with Parkinson's disease</measure>
      <time_frame>Day14,Day28,Day56</time_frame>
      <description>the score of Berg Balance Scale (BBS)[0-56] The higher the score, the better the balance</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of sleep structure in patients with Parkinson's disease</measure>
      <time_frame>Day14,Day28,Day56</time_frame>
      <description>Use polysomnography (PSG) to record the proportion of slow-wave sleep</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of low-frequency rTMS stimulation on anxiety</measure>
      <time_frame>Day14,Day28,Day56</time_frame>
      <description>the score of Hamilton Anxiety Rating Scale（HAMA)[0-64] The higher the score, the more anxious</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of low-frequency rTMS stimulation on cognition</measure>
      <time_frame>Day14,Day28,Day56</time_frame>
      <description>the score of Montreal Cognitive Assessment（Moca)[0-30] The lower the score, the more severe the cognitive dysfunction</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of low-frequency rTMS stimulation on cortical excitability</measure>
      <time_frame>Day14,Day28</time_frame>
      <description>short-interval cortical inhibition(SICI)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of low-frequency rTMS stimulation on depression</measure>
      <time_frame>Day14,Day28,Day56</time_frame>
      <description>the score of Hamilton Depression Rating Scale（HAMD） Total score ≥ 20 points: may be mild or moderate depression; The higher the score, the more depressed</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Assessment of daytime sleepiness in patients with Parkinson's disease</measure>
      <time_frame>Day14,Day28,Day56</time_frame>
      <description>the score of The Epworth Sleeping Scale(ESS)[0-24] The higher the score, the more lethargic</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of low-frequency rTMS stimulation on gait</measure>
      <time_frame>Day14,Day28,Day56</time_frame>
      <description>Use a quantitative gait analysis system to analyze the change of gait</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Effects of low-frequency rTMS stimulation on brain connectivity in the PD brain</measure>
      <time_frame>Day0,Day14,Day28</time_frame>
      <description>functional magnetic resonance imaging (fMRI) (Default mode network, DMN）</description>
    </other_outcome>
    <other_outcome>
      <measure>Changes in salivary melatonin levels</measure>
      <time_frame>Day0,Day14,Day28,Day56</time_frame>
      <description>salivary melatonin levels(Fasting)</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">56</enrollment>
    <condition>Parkinson's Disease</condition>
    <arm_group>
      <arm_group_label>the early treatment group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>stage1+stage2 real stimulation</description>
    </arm_group>
    <arm_group>
      <arm_group_label>the control group (delayed treatment group)</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>stage1 sham stimulation + stage2 real stimulation</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>rTMS real stimulation stage1</intervention_name>
      <description>In the first stage, the early treatment group use low-frequency rTMS real stimulation,</description>
      <arm_group_label>the early treatment group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>rTMS shame stimulation stage1</intervention_name>
      <description>In the first stage, the control group (delayed treatment group) all use sham stimulation.</description>
      <arm_group_label>the control group (delayed treatment group)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>rTMS real stimulation stage 2</intervention_name>
      <description>In the second stage, both the early treatment group and the control group (delayed treatment group) will be treated with true stimulation low-frequency rTMS.</description>
      <arm_group_label>the control group (delayed treatment group)</arm_group_label>
      <arm_group_label>the early treatment group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Meet the clinically definite or clinically probable PD according to the MDS 2015&#xD;
               version.&#xD;
  &#xD;
            2. Chinese Han population (three generations), age greater than or equal to 50 years old,&#xD;
               less than or equal to 80 years old, male or female.&#xD;
  &#xD;
            3. Hoehn-Yahr stages 1-4.&#xD;
  &#xD;
            4. The dose of levodopa drug therapy was stable three weeks before enrollment and during&#xD;
               the follow-up period.&#xD;
  &#xD;
            5. Right-handed.&#xD;
  &#xD;
            6. The patient signed a written informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Any form of Parkinsonism other than primary PD.&#xD;
  &#xD;
            2. Those who have received neurosurgical intervention or stereotaxic brain surgery for&#xD;
               PD, or have previously received TMS treatment.&#xD;
  &#xD;
            3. Cognitive dysfunction (MMSE ≤ 24 points) or those who cannot cooperate with the scale&#xD;
               score.&#xD;
  &#xD;
            4. Persons with mental disabilities.&#xD;
  &#xD;
            5. Pregnant women.&#xD;
  &#xD;
            6. There are contraindications for rTMS treatment.&#xD;
  &#xD;
            7. There are contraindications for MRI examination.&#xD;
  &#xD;
            8. Baseline PSG suggests other sleep disorders such as moderate to severe OSAS; BMI&gt;=30.&#xD;
  &#xD;
            9. Patients who are addicted to alcohol, taking SSRIs, TCAs, sedative hypnotics,&#xD;
               histamine antagonists and other drugs and food that may affect NREM and REM sleep&#xD;
               structure.&#xD;
  &#xD;
           10. Those who are unwilling to participate in the study or unable to sign the informed&#xD;
               consent form; and other circumstances that the researcher considers inappropriate to&#xD;
               participate in the study.&#xD;
  &#xD;
               -&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>50 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Xiaoying Zhu, doctor</last_name>
      <phone>+86 21 63240090</phone>
      <email>docxiaoying@163.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
      <investigator_full_name>Xiaoying Zhu</investigator_full_name>
      <investigator_title>associate chief physician of neurology</investigator_title>
    </responsible_party>
    <keyword>Parkinson's disease</keyword>
    <keyword>slow-wave sleep</keyword>
    <keyword>rTMS</keyword>
    <keyword>motor symptom</keyword>
    <keyword>progression</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Parkinson Disease</mesh_term>
      <mesh_term>Disease Progression</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/NCT06002581
  org study id: CCTR-2022B05
  nct id: NCT06002581
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  At present, no drug therapy has been proven to delay the progression of Parkinson's disease
        (PD). rTMS, as a non-invasive neuromodulation method, can regulate Slow-wave sleep (SWS). SWS
        is recognized closely related to neurodegeneration. However, there has been no clinical
        studies on if rTMS could delay the progression of PD by regulating SWS.
  
        The main purpose of this study is to explore the changes of SWS in non-rapid eye movement
        (NREM) sleep period in PD patients by using rTMS, and the relationship with potential
        improvements of SWS and motor symptom delay. The study aims to find a potential new treatment
        strategy to delay the neurodegenerative process in PD patients by modulating SWS by rTMS.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Outcomes Assessor)
  measure: Change of Motor Function in PD by Low Frequency rTMS Stimulation
  time frame: Day14
  description: the score of Unified Parkinson's Disease Rating ScaleⅢ (UPDRSIII)[off] The higher the score, the more severe the motor dysfunction
  measure: Effects of low-frequency rTMS stimulation on motor symptoms
  time frame: Day28,Day56
  description: the score of Unified Parkinson's Disease Rating ScaleⅢ (UPDRSIII) [on] The higher the score, the more severe the motor dysfunction
  measure: Measurement of improved balance function in patients with Parkinson's disease
  time frame: Day14,Day28,Day56
  description: the score of Berg Balance Scale (BBS)[0-56] The higher the score, the better the balance
  measure: Assessment of sleep structure in patients with Parkinson's disease
  time frame: Day14,Day28,Day56
  description: Use polysomnography (PSG) to record the proportion of slow-wave sleep
  measure: Effects of low-frequency rTMS stimulation on anxiety
  time frame: Day14,Day28,Day56
  description: the score of Hamilton Anxiety Rating Scale（HAMA)[0-64] The higher the score, the more anxious
  measure: Effects of low-frequency rTMS stimulation on cognition
  time frame: Day14,Day28,Day56
  description: the score of Montreal Cognitive Assessment（Moca)[0-30] The lower the score, the more severe the cognitive dysfunction
  measure: Effects of low-frequency rTMS stimulation on cortical excitability
  time frame: Day14,Day28
  description: short-interval cortical inhibition(SICI)
  measure: Effects of low-frequency rTMS stimulation on depression
  time frame: Day14,Day28,Day56
  description: the score of Hamilton Depression Rating Scale（HAMD） Total score ≥ 20 points: may be mild or moderate depression; The higher the score, the more depressed
  measure: Assessment of daytime sleepiness in patients with Parkinson's disease
  time frame: Day14,Day28,Day56
  description: the score of The Epworth Sleeping Scale(ESS)[0-24] The higher the score, the more lethargic
  measure: Effects of low-frequency rTMS stimulation on gait
  time frame: Day14,Day28,Day56
  description: Use a quantitative gait analysis system to analyze the change of gait
  measure: Effects of low-frequency rTMS stimulation on brain connectivity in the PD brain
  time frame: Day0,Day14,Day28
  description: functional magnetic resonance imaging (fMRI) (Default mode network, DMN）
  measure: Changes in salivary melatonin levels
  time frame: Day0,Day14,Day28,Day56
  description: salivary melatonin levels(Fasting)
  arm group label: the early treatment group
  arm group type: Experimental
  description: stage1+stage2 real stimulation
  arm group label: the control group (delayed treatment group)
  arm group type: Other
  description: stage1 sham stimulation + stage2 real stimulation
  intervention type: Device
  intervention name: rTMS real stimulation stage1
  description: In the first stage, the early treatment group use low-frequency rTMS real stimulation,
  arm group label: the early treatment group
  intervention type: Device
  intervention name: rTMS shame stimulation stage1
  description: In the first stage, the control group (delayed treatment group) all use sham stimulation.
  arm group label: the control group (delayed treatment group)
  intervention type: Device
  intervention name: rTMS real stimulation stage 2
  description: In the second stage, both the early treatment group and the control group (delayed treatment group) will be treated with true stimulation low-frequency rTMS.
  arm group label: the control group (delayed treatment group)
  arm group label: the early treatment group
  criteria: 
  gender: All
  minimum age: 50 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Xiaoying Zhu, doctor
  phone: +86 21 63240090
  email: docxiaoying@163.com
  responsible party type: Principal Investigator
  investigator affiliation: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
  investigator full name: Xiaoying Zhu
  investigator title: associate chief physician of neurology
  mesh term: Parkinson Disease
  mesh term: Disease Progression