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/NCT06005363</url>
    </required_header>
    <id_info>
      <org_study_id>CMRPG3N0591</org_study_id>
      <nct_id>NCT06005363</nct_id>
    </id_info>
    <brief_title>CSF Metabolomics and Glymphatic Function in Patients Receiving VP- Shunt Surgery.</brief_title>
    <official_title>The Application of Anesthesia Depth Monitoring on Post-operative Cognitive Dysfunction for Patients With Hydrocephalus Receiving Ventricular-peritoneal Shunt Surgery and Associated Change in CSF Metabolomics and Glymphatic Function.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chang Gung Memorial Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Chang Gung Memorial Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        In this randomized control study, the investigators intended to evaluate the influence of&#xD;
        different anesthetics on postoperative cognitive dysfunction, neuroinflammation, CSF&#xD;
        metabolomics, and glymphatic function in patients with normal pressure hydrocephalus for VP&#xD;
        shunt surgery. The investigators assume that the use of dexmedetomidine infusion and proper&#xD;
        anesthsia depth during general anesthesia, in addition to multi-model analgesia, might be&#xD;
        helpful to enhance glymphatic function, reduce neuroinflammation, and decrease postoperative&#xD;
        cognitive dysfunction.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        In this prospective randomized controlled study, 48 patients with communicating hydrocephalus&#xD;
        will be enrolled in the study and these patients will be divided into 3 groups in which&#xD;
        intervention group received anesthesia depth monitoring (BIS group and DEX group) and&#xD;
        dexmedetomidine infusion (DEX group), while the controlled group received usual anesthesia&#xD;
        care without dexmedetomidine during VP shunt surgery. The participant's intraoperative CSF&#xD;
        and plasma samples will be collected for biochemical analysis and metabolomic analysis. The&#xD;
        investigators will use two analytical metabolomic platforms, including nuclear magnetic&#xD;
        resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS), to execute quantitative&#xD;
        metabolomics on human CSF and plasma samples. These metabolomic data will be compared with&#xD;
        previous established human aging CSF Metabolome Database. After VP shunt surgery, these&#xD;
        patient's glymphatic function will be evaluated with 3T functional MRI. The postoperative&#xD;
        cognitive function and delirium status of these patients will be evaluated for the following&#xD;
        3 days using MMSE score, Montreal Cognitive Assessment, and CAM-ICU score. During analysis,&#xD;
        the pre-operative metabolomic signature of patients with postoperative cognitive&#xD;
        dysfunction(POCD) will be compared with patients without POCD to profile the metabolomics of&#xD;
        POCD. Besides, the investigators could examine the correlation of glymphatic function and&#xD;
        POCD. By comparing the CSF metabolomic change in these three groups, the investigators could&#xD;
        evaluate the the efficacy of anesthesia depth monitoring and dexmedetomidine to reduce POCD&#xD;
        development during VP shunt surgery. The result of this study might be able to explain the&#xD;
        brain pathophysiology of POCD, the role of glymphatic function in POCD, metabolomic signature&#xD;
        of POCD, and establish a better anesthesia regimen to reduce the development of POCD.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 1, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">June 30, 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>
      <intervention_model_description>Two interventional group with BIS group and DEX group all receive BIS monitoring, and DEX group receive dexmedetomidine infusion.</intervention_model_description>
      <primary_purpose>Diagnostic</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
      <masking_description>Participants receive randomized allocation to BIS, DEX, or usual care group before VP shunt surgery. Outcome assessor evaluate the preoperative and postoperative cognitive function, delirium status, and evaluate glymphatic function with functional MRI.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Postoperative cognitive function</measure>
      <time_frame>postoperative 2 hours, postoperative day 1, postoperative day 2, postoperative day 3</time_frame>
      <description>MMSE, MoCA, CAM-ICU score</description>
    </primary_outcome>
    <primary_outcome>
      <measure>NMR amd LC-MS CSF and plasma metabolomics</measure>
      <time_frame>preoperative, postoperative 2 hours, postoperative day 1</time_frame>
      <description>NMR and LC-MS metabolomics of CSF and plasma samples</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Neuroinflammation parameters</measure>
      <time_frame>preoperative, postoperative 2 hours, postoperative day 1</time_frame>
      <description>lactate, tau protein, amyloid beta, orexin, IL-6, IL-10, TNF-alpha, s100b</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Glymphatic function</measure>
      <time_frame>preoperative, postoperative day 1</time_frame>
      <description>evaluate DTI-ALPS index in 3T functional MRI</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">48</enrollment>
    <condition>The Association of Postoperative Cognitive Dysfunction With Glymphatic Function and Neuroinflammation</condition>
    <condition>The Association of Postoperative Cognitive Dysfunction With CSF Metabolomic Change</condition>
    <arm_group>
      <arm_group_label>BIS group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Use BIS monitoring to adjust intraoperative anesthetics.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>DEX group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>use BIS monitoring to adjust anesthetics and give dexmedetomidine infusion.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Usual group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>usual care with 1 MAC sevoflurane maintainance.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Dexmedetomidine</intervention_name>
      <description>dexmedetomidine infusion</description>
      <arm_group_label>DEX group</arm_group_label>
      <other_name>DEX</other_name>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>anesthesia depth monitoring</intervention_name>
      <description>intraoperative anesthesia depth monitoring to keep BIS 40-60</description>
      <arm_group_label>BIS group</arm_group_label>
      <arm_group_label>DEX group</arm_group_label>
      <other_name>BIS</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  patients with communicating hydrocephalus for elective VP shunt surgery under general&#xD;
               anesthesia&#xD;
  &#xD;
            -  age&gt; 60 y/o&#xD;
  &#xD;
            -  conscious clear&#xD;
  &#xD;
            -  fluency in Chinese&#xD;
  &#xD;
            -  anticipated hospital stay ≥ 3 days after surgery&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  unstable preoperative condition (unstable angina, CHF, asthma attack) within 4 weeks&#xD;
               before surgery,&#xD;
  &#xD;
            -  severe hepatic dysfunction or renal failure&#xD;
  &#xD;
            -  history of neuropsychological diseases such as schizophrenia, Parkinson's disease,&#xD;
               dementia, stroke,&#xD;
  &#xD;
            -  pre-op cognitive impairment,&#xD;
  &#xD;
            -  preoperative delirium,&#xD;
  &#xD;
            -  preoperative depression,&#xD;
  &#xD;
            -  allergy to contrast medium of MRI.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>60 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Huan-tang Lin</last_name>
      <role>Principal Investigator</role>
      <affiliation>Department of anesthesiology, Linkou Chang Gung Memorial Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Huan-Tang Lin, MD</last_name>
      <phone>+886-33281200</phone>
      <phone_ext>2324</phone_ext>
      <email>sanctuary12@cgmh.org.tw</email>
    </overall_contact>
    <location>
      <facility>
        <name>Linkou Chang Gung Memorial Hospital</name>
        <address>
          <city>Taoyuan</city>
          <zip>33305</zip>
          <country>Taiwan</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Huan-tang Lin</last_name>
        <phone>033281200</phone>
        <phone_ext>2324</phone_ext>
        <email>sanctuary12@cgmh.org.tw</email>
      </contact>
    </location>
    <location_countries>
      <country>Taiwan</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>anesthesia depth monitoring</keyword>
    <keyword>postoperative cognitive dysfunction</keyword>
    <keyword>metabolomics</keyword>
    <keyword>cerebrospinal fluid</keyword>
    <keyword>glymphatic function</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neuroinflammatory Diseases</mesh_term>
      <mesh_term>Postoperative Cognitive Complications</mesh_term>
      <mesh_term>Cognitive Dysfunction</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Dexmedetomidine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>personal data is encrypted</ipd_description>
    </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/NCT06005363
  org study id: CMRPG3N0591
  nct id: NCT06005363
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  In this randomized control study, the investigators intended to evaluate the influence of
        different anesthetics on postoperative cognitive dysfunction, neuroinflammation, CSF
        metabolomics, and glymphatic function in patients with normal pressure hydrocephalus for VP
        shunt surgery. The investigators assume that the use of dexmedetomidine infusion and proper
        anesthsia depth during general anesthesia, in addition to multi-model analgesia, might be
        helpful to enhance glymphatic function, reduce neuroinflammation, and decrease postoperative
        cognitive dysfunction.
  In this prospective randomized controlled study, 48 patients with communicating hydrocephalus
        will be enrolled in the study and these patients will be divided into 3 groups in which
        intervention group received anesthesia depth monitoring (BIS group and DEX group) and
        dexmedetomidine infusion (DEX group), while the controlled group received usual anesthesia
        care without dexmedetomidine during VP shunt surgery. The participant's intraoperative CSF
        and plasma samples will be collected for biochemical analysis and metabolomic analysis. The
        investigators will use two analytical metabolomic platforms, including nuclear magnetic
        resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS), to execute quantitative
        metabolomics on human CSF and plasma samples. These metabolomic data will be compared with
        previous established human aging CSF Metabolome Database. After VP shunt surgery, these
        patient's glymphatic function will be evaluated with 3T functional MRI. The postoperative
        cognitive function and delirium status of these patients will be evaluated for the following
        3 days using MMSE score, Montreal Cognitive Assessment, and CAM-ICU score. During analysis,
        the pre-operative metabolomic signature of patients with postoperative cognitive
        dysfunction(POCD) will be compared with patients without POCD to profile the metabolomics of
        POCD. Besides, the investigators could examine the correlation of glymphatic function and
        POCD. By comparing the CSF metabolomic change in these three groups, the investigators could
        evaluate the the efficacy of anesthesia depth monitoring and dexmedetomidine to reduce POCD
        development during VP shunt surgery. The result of this study might be able to explain the
        brain pathophysiology of POCD, the role of glymphatic function in POCD, metabolomic signature
        of POCD, and establish a better anesthesia regimen to reduce the development of POCD.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Two interventional group with BIS group and DEX group all receive BIS monitoring, and DEX group receive dexmedetomidine infusion.
  primary purpose: Diagnostic
  masking: Double (Participant, Outcomes Assessor)
  masking description: Participants receive randomized allocation to BIS, DEX, or usual care group before VP shunt surgery. Outcome assessor evaluate the preoperative and postoperative cognitive function, delirium status, and evaluate glymphatic function with functional MRI.
  measure: Postoperative cognitive function
  time frame: postoperative 2 hours, postoperative day 1, postoperative day 2, postoperative day 3
  description: MMSE, MoCA, CAM-ICU score
  measure: NMR amd LC-MS CSF and plasma metabolomics
  time frame: preoperative, postoperative 2 hours, postoperative day 1
  description: NMR and LC-MS metabolomics of CSF and plasma samples
  measure: Neuroinflammation parameters
  time frame: preoperative, postoperative 2 hours, postoperative day 1
  description: lactate, tau protein, amyloid beta, orexin, IL-6, IL-10, TNF-alpha, s100b
  measure: Glymphatic function
  time frame: preoperative, postoperative day 1
  description: evaluate DTI-ALPS index in 3T functional MRI
  arm group label: BIS group
  arm group type: Experimental
  description: Use BIS monitoring to adjust intraoperative anesthetics.
  arm group label: DEX group
  arm group type: Experimental
  description: use BIS monitoring to adjust anesthetics and give dexmedetomidine infusion.
  arm group label: Usual group
  arm group type: No Intervention
  description: usual care with 1 MAC sevoflurane maintainance.
  intervention type: Drug
  intervention name: Dexmedetomidine
  description: dexmedetomidine infusion
  arm group label: DEX group
  other name: DEX
  intervention type: Device
  intervention name: anesthesia depth monitoring
  description: intraoperative anesthesia depth monitoring to keep BIS 40-60
  arm group label: BIS group
  arm group label: DEX group
  other name: BIS
  criteria: 
  gender: All
  minimum age: 60 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Huan-tang Lin
  role: Principal Investigator
  affiliation: Department of anesthesiology, Linkou Chang Gung Memorial Hospital
  last name: Huan-Tang Lin, MD
  phone: +886-33281200
  phone ext: 2324
  email: sanctuary12@cgmh.org.tw
  facility: 
  status: Recruiting
  contact: 
  country: Taiwan
  responsible party type: Sponsor
  mesh term: Neuroinflammatory Diseases
  mesh term: Postoperative Cognitive Complications
  mesh term: Cognitive Dysfunction
  mesh term: Dexmedetomidine
  sharing ipd: No
  ipd description: personal data is encrypted