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/NCT05985993</url>
    </required_header>
    <id_info>
      <org_study_id>2022JC009</org_study_id>
      <nct_id>NCT05985993</nct_id>
    </id_info>
    <brief_title>Precise Intervention Technology and Application of Low Intensity TUS on Negative Symptoms of Schizophrenia</brief_title>
    <official_title>Precise Intervention Technology and Application of Low Intensity Transcranial Ultrasound Stimulation (TUS) on Negative Symptoms of Schizophrenia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shanghai Mental Health Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shanghai Mental Health Center</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>
        Based on the current background and our previous studies, TUS has been proved that rTUS&#xD;
        intervention could induce long-term potentiation like (LTP-like) plasticity and neuromodulate&#xD;
        the brain cortex in schizophrenia patients. rTUS over the left dorsolateral prefrontal cortex&#xD;
        (DLPFC) can alleviate the negative symptoms in schizophrenia. In this double-blind,&#xD;
        randomized, sham-controlled study, the efficacy of different treatment options and mechanisms&#xD;
        of low-intensity rTUS on negative symptoms will be investigated.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Negative symptoms is a core symptom of schizophrenia related to poor functional outcome which&#xD;
        remains largely treatment refractory. Prior studies indicated that abnormalities in the&#xD;
        prefrontal-temporal circuit and glutamate/GABA imbalances may be the root causes of negative&#xD;
        symptoms. Transcranial ultrasound stimulation (TUS), an emerging non-invasive neuromodulation&#xD;
        technique, can modulate neural excitability and plasticity in the prefrontal and temporal&#xD;
        cortex. In this double-blind, randomized, sham-controlled study, the efficacy of different&#xD;
        treatment options and mechanisms of low-intensity rTUS on negative symptoms will be&#xD;
        investigated. A total of 102 schizophrenia inpatients will be recruited and randomly&#xD;
        allocated into single-target group (left DLPFC), both-target group (both left DLPFC and right&#xD;
        STG) or sham group in ratio of 1:1:1. This study aims to determine the efficacy of TUS and to&#xD;
        reveal its underlying neural mechanism. MEPs, fNIRS ,and multi-modal MRI will be detected.&#xD;
        Neuropsychological assessments will also be conducted to develop the optimized treatment&#xD;
        strategy. The study points to a novel and promising therapeutic neuromodulation approach that&#xD;
        may improve the functional outcome of schizophrenia, which has been the main cause of mental&#xD;
        disability.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2025</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 from baseline in the Scale for Assessment of Negative Symptoms(SANS)</measure>
      <time_frame>baseline, 4 weeks and 8 weeks</time_frame>
      <description>Change from baseline in the Scale for Assessment of Negative Symptoms(SANS) at 4 weeks and 8 weeks. The minimum to maximum value is 0-120. Lower scores mean a better outcome.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in Positive and Negative Syndrome Scale(PANSS)</measure>
      <time_frame>baseline, 4 weeks and 8 weeks</time_frame>
      <description>Change from baseline in Positive and Negative Syndrome Scale(PANSS) at 4 weeks and 8 weeks. The minimum to maximum value is 30-210. Lower scores mean a better outcome.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cognitive Function</measure>
      <time_frame>baseline, 4 weeks and 8 weeks</time_frame>
      <description>Change from baseline in MATRICS MCCB</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of Multi-modal Brain Neuroimaging in structure</measure>
      <time_frame>baseline and 4 weeks</time_frame>
      <description>Brain structure data will be acquired.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of Multi-modal Brain Neuroimaging in resting- state fMRI</measure>
      <time_frame>baseline and 4 weeks</time_frame>
      <description>Resting-state fMRI data will be acquired.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of Multi-modal Brain Neuroimaging in 1H-MRS</measure>
      <time_frame>baseline and 4 weeks</time_frame>
      <description>1H-MRS data will be acquired.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change of functional near-infrared spectroscopy (fNIRS)</measure>
      <time_frame>baseline</time_frame>
      <description>Functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging technique that reflects changes in Oxy-Hb and Deoxy-Hb during brain activity, will be measured on left M1 region at baseline to evaluate the neuromodulation effect of TUS on neural activity.</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">102</enrollment>
    <condition>Negative Symptoms of Schizophrenia</condition>
    <arm_group>
      <arm_group_label>single-target group (left DLPFC)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>34 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC</description>
    </arm_group>
    <arm_group>
      <arm_group_label>both-target group (both left DLPFC and right STG)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>34 eligible patients will be treated with active TUS for 4 weeks on the both left DLPFC and right STG</description>
    </arm_group>
    <arm_group>
      <arm_group_label>sham group</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>34 eligible patients will be treated with sham TUS for 4 weeks on the left DLPFC</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>low-intensity transcranial ultrasound stimulation (TUS)</intervention_name>
      <description>The rTUS was administered using an immersion-type focused ultrasound transducer (V391-SU, Olympus NDT, Waltham, USA). Low-intensity transcranial ultrasound stimulation on the target. Duration:20 days (workdays for four consecutive weeks).</description>
      <arm_group_label>both-target group (both left DLPFC and right STG)</arm_group_label>
      <arm_group_label>sham group</arm_group_label>
      <arm_group_label>single-target group (left DLPFC)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Meet the DSM-5 diagnostic criteria for schizophrenia or schizoaffective disorder;&#xD;
  &#xD;
            -  Age18-50, right-handed, Han nationality;&#xD;
  &#xD;
            -  Score of at least 1 item from N1 to N7 in PANSS is ≥4 (moderate or above);&#xD;
  &#xD;
            -  Be in a stable condition, received second-generation antipsychotics for at least 4&#xD;
               weeks or more;&#xD;
  &#xD;
            -  Written informed consent;&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Current or past neurological illness, severe physical diseases, substance abuse or&#xD;
               alcohol dependence, mental retardation, pregnant or lactation;&#xD;
  &#xD;
            -  Uncooperative or risky patients with high excitement, stupor, disorder of words and&#xD;
               deeds, negative suicide, etc.;&#xD;
  &#xD;
            -  History of MECT or other physical therapy within 6 months;&#xD;
  &#xD;
            -  History of epilepsy, or epileptic waves on the baseline EEG;&#xD;
  &#xD;
            -  Ruled out share antiepileptic drugs, carbamazepine, valproic acid salt) or larger&#xD;
               doses of benzodiazepines drugs (&gt; 10 mg/day, diazepam clonazepam 2 mg/day, 1 mg/day,&#xD;
               alprazolam lorazepam 2 mg/day, midazolam 10 mg/day, 20 mg/day, Mr Shah diazepam&#xD;
               triazolam 0.5 mg/day), avoid the use of chlorine drug, (in principle, to avoid the use&#xD;
               of antiepileptic drugs and clonazepam;Other antipsychotic drugs, if necessary, remain&#xD;
               unchanged during the course of treatment;&#xD;
  &#xD;
            -  Contraindications to TUS and MRI are present.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>50 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Dengtang LIU</last_name>
      <phone>021-34773434</phone>
      <email>erliu110@126.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shanghai Mental Health Center</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200030</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Dengtang LIU</last_name>
        <phone>021-34773434</phone>
        <email>erliu110@126.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 10, 2023</last_update_submitted>
    <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Shanghai Mental Health Center</investigator_affiliation>
      <investigator_full_name>Dengtang LIU</investigator_full_name>
      <investigator_title>Chief Psychiatrist and Professor</investigator_title>
    </responsible_party>
    <keyword>Schizophrenia</keyword>
    <keyword>Negative Symptoms</keyword>
    <keyword>Transcranial Ultrasound Stimulation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Schizophrenia</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05985993
  org study id: 2022JC009
  nct id: NCT05985993
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Based on the current background and our previous studies, TUS has been proved that rTUS
        intervention could induce long-term potentiation like (LTP-like) plasticity and neuromodulate
        the brain cortex in schizophrenia patients. rTUS over the left dorsolateral prefrontal cortex
        (DLPFC) can alleviate the negative symptoms in schizophrenia. In this double-blind,
        randomized, sham-controlled study, the efficacy of different treatment options and mechanisms
        of low-intensity rTUS on negative symptoms will be investigated.
  Negative symptoms is a core symptom of schizophrenia related to poor functional outcome which
        remains largely treatment refractory. Prior studies indicated that abnormalities in the
        prefrontal-temporal circuit and glutamate/GABA imbalances may be the root causes of negative
        symptoms. Transcranial ultrasound stimulation (TUS), an emerging non-invasive neuromodulation
        technique, can modulate neural excitability and plasticity in the prefrontal and temporal
        cortex. In this double-blind, randomized, sham-controlled study, the efficacy of different
        treatment options and mechanisms of low-intensity rTUS on negative symptoms will be
        investigated. A total of 102 schizophrenia inpatients will be recruited and randomly
        allocated into single-target group (left DLPFC), both-target group (both left DLPFC and right
        STG) or sham group in ratio of 1:1:1. This study aims to determine the efficacy of TUS and to
        reveal its underlying neural mechanism. MEPs, fNIRS ,and multi-modal MRI will be detected.
        Neuropsychological assessments will also be conducted to develop the optimized treatment
        strategy. The study points to a novel and promising therapeutic neuromodulation approach that
        may improve the functional outcome of schizophrenia, which has been the main cause of mental
        disability.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Outcomes Assessor)
  measure: Change from baseline in the Scale for Assessment of Negative Symptoms(SANS)
  time frame: baseline, 4 weeks and 8 weeks
  description: Change from baseline in the Scale for Assessment of Negative Symptoms(SANS) at 4 weeks and 8 weeks. The minimum to maximum value is 0-120. Lower scores mean a better outcome.
  measure: Change from baseline in Positive and Negative Syndrome Scale(PANSS)
  time frame: baseline, 4 weeks and 8 weeks
  description: Change from baseline in Positive and Negative Syndrome Scale(PANSS) at 4 weeks and 8 weeks. The minimum to maximum value is 30-210. Lower scores mean a better outcome.
  measure: Cognitive Function
  time frame: baseline, 4 weeks and 8 weeks
  description: Change from baseline in MATRICS MCCB
  measure: Change of Multi-modal Brain Neuroimaging in structure
  time frame: baseline and 4 weeks
  description: Brain structure data will be acquired.
  measure: Change of Multi-modal Brain Neuroimaging in resting- state fMRI
  time frame: baseline and 4 weeks
  description: Resting-state fMRI data will be acquired.
  measure: Change of Multi-modal Brain Neuroimaging in 1H-MRS
  time frame: baseline and 4 weeks
  description: 1H-MRS data will be acquired.
  measure: Change of functional near-infrared spectroscopy (fNIRS)
  time frame: baseline
  description: Functional near-infrared spectroscopy (fNIRS), a non-invasive neuroimaging technique that reflects changes in Oxy-Hb and Deoxy-Hb during brain activity, will be measured on left M1 region at baseline to evaluate the neuromodulation effect of TUS on neural activity.
  arm group label: single-target group (left DLPFC)
  arm group type: Active Comparator
  description: 34 eligible patients will be treated with active TUS for 4 weeks on the left DLPFC
  arm group label: both-target group (both left DLPFC and right STG)
  arm group type: Active Comparator
  description: 34 eligible patients will be treated with active TUS for 4 weeks on the both left DLPFC and right STG
  arm group label: sham group
  arm group type: Sham Comparator
  description: 34 eligible patients will be treated with sham TUS for 4 weeks on the left DLPFC
  intervention type: Device
  intervention name: low-intensity transcranial ultrasound stimulation (TUS)
  description: The rTUS was administered using an immersion-type focused ultrasound transducer (V391-SU, Olympus NDT, Waltham, USA). Low-intensity transcranial ultrasound stimulation on the target. Duration:20 days (workdays for four consecutive weeks).
  arm group label: both-target group (both left DLPFC and right STG)
  arm group label: sham group
  arm group label: single-target group (left DLPFC)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 50 Years
  healthy volunteers: No
  last name: Dengtang LIU
  phone: 021-34773434
  email: erliu110@126.com
  facility: 
  contact: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Shanghai Mental Health Center
  investigator full name: Dengtang LIU
  investigator title: Chief Psychiatrist and Professor
  mesh term: Schizophrenia
  sharing ipd: No