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/NCT05990556</url>
    </required_header>
    <id_info>
      <org_study_id>ZNu</org_study_id>
      <nct_id>NCT05990556</nct_id>
    </id_info>
    <brief_title>Research on the Safety and Efficacy of Blocking Dural Blood Supply in Glioblastoma Patients</brief_title>
    <official_title>Research on the Safety and Efficacy of Blocking Dural Blood Supply in Glioblastoma Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhang Nu</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>First Affiliated Hospital, Sun Yat-Sen University</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>
        Glioblastoma is the most common primary malignancy of the central nervous system with a very&#xD;
        poor prognosis. Most of the immunotherapies that have made significant breakthroughs in the&#xD;
        treatment of other tumors in recent years are unsatisfactory in the application of&#xD;
        glioblastoma, which is mainly inseparable from the highly inhibitory immune microenvironment&#xD;
        formed by the latter. Therefore, how to change this &quot;immune desert&quot; and better activate&#xD;
        immune effector cells to play an anti-tumor effect is currently a hot spot in glioma immune&#xD;
        research. In recent years, there has been continuous research support that the myeloid cells&#xD;
        of the central nervous system are partly derived from the bone marrow of the skull, and there&#xD;
        is a special channel connection between the skull and the dura mater, through which immune&#xD;
        cells can be transported. This suggests that some of the tumor-associated macrophages&#xD;
        recruited in the glioblastoma microenvironment may be passed through the dura mater. In&#xD;
        previous animal experiments, we blocked the main blood supply to the dura mater by ligating&#xD;
        the bilateral external carotid arteries of mice, cutting off the potential supply of dura&#xD;
        mater to suppressor myeloid cells in the lesion. The results showed that after ligation of&#xD;
        bilateral external carotid arteries, the survival period of tumor-forming mice was&#xD;
        significantly prolonged and the prognosis was improved. The proportion of myeloid cells in&#xD;
        the tumor microenvironment of mice decreased significantly, and the expression of tumor&#xD;
        suppressor molecules such as arginase Arg1 decreased, indicating that the improvement of&#xD;
        mouse prognosis was closely related to the proportion and phenotypic changes of myeloid cells&#xD;
        after dural blood supply blockade. The meningeal lymphatic system of the human central&#xD;
        nervous system has been shown to be an important part of the immune system, while the&#xD;
        external carotid artery system, the main source of blood supply to the dura, carries abundant&#xD;
        immune cells that ooze out to the dura mater through the endothelial window hole of the dural&#xD;
        blood vessel, which is an important source of dural immune cells. In the glioblastoma immune&#xD;
        microenvironment, the source of immune cells includes dural branches from the external&#xD;
        carotid artery system in addition to branches of the internal carotid artery system.&#xD;
        Therefore, for patients diagnosed with glioblastoma, this study involves embolization of the&#xD;
        dural branch of the external carotid artery system (bilateral middle meningeal artery) to&#xD;
        block the dural blood supply before craniotomy. At the same time, microsurgery under&#xD;
        multimodal image navigation was used to remove the tumor. It is expected to be effective in&#xD;
        reducing the proportion of myeloid suppressor cells in the tumor microenvironment, slowing&#xD;
        the growth rate of residual tumor cells, and prolonging the tumor-free progression and&#xD;
        survival of patients.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>Interventional single-arm studies, no grouping.&#xD;
  1 Randomize groupings 1.1 Method for generating random sequence assignments This study is a real-world study, it is planned to include 20 patients as a case, there is no need for random sequence and blinded allocation before intervention, the patient's condition, experimental purpose, experimental method and possible risks are informed before surgery, and the patient chooses whether to undergo preoperative interventional surgery to block bilateral meningeal blood supply.&#xD;
  1.2 Randomly assigned hiding This is a real-world study that intends to include three patients as individual cases without random sequencing prior to intervention and therefore does not involve allocation concealment.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
      <masking_description>Blinding and unblinding This is a real-world study that intends to include three patients as case studies without blinding prior to intervention and therefore does not involve blinding.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Patient survival period</measure>
      <time_frame>15 months</time_frame>
      <description>The overall survival of enrolled patients was compared with the overall survival reported in the literature</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Postoperative recurring time</measure>
      <time_frame>3-6 months</time_frame>
      <description>The Postoperative recurring time in enrolled patients was compared with the mean time in the literature</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Glioblastoma</condition>
    <condition>Meningeal Arteries</condition>
    <arm_group>
      <arm_group_label>interventional procedure to block bilateral meningeal blood supply</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>interventional procedure to block bilateral meningeal blood supply</intervention_name>
      <description>The embolic agent used in bilateral meningeal blood supply occlusion through interventional surgery is Onyx glue (&quot;liquid embolic system&quot;). After the location of bilateral middle meningeal artery was determined by femoral artery puncture angiography, SL-10 was sent to the opening of bilateral middle meningeal artery through guiding catheter, and Onxy glue was used to block the bilateral middle meningeal artery. The standard of embolization was that the middle meningeal artery was not seen and Onyx glue was not diffused to the petrous branch of the middle meningeal artery. In order to avoid dangerous anastomotic branches and complications, attention should be paid to superselecting the middle meningeal artery and slowly injecting Onyx glue during the operation. After embolization of the middle meningeal artery by interventional surgery, glioblastoma was removed immediately under the guidance of multimodal imaging.</description>
      <arm_group_label>interventional procedure to block bilateral meningeal blood supply</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Imaging or needle biopsy pathologically diagnosed as glioblastoma&#xD;
  &#xD;
            -  Patients have not previously received radiotherapy, chemotherapy and other treatment&#xD;
               modalities for intracranial lesions&#xD;
  &#xD;
            -  There are no related contraindications such as neurovascular intervention and&#xD;
               craniotomy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  The patient's initial imaging diagnosis was glioblastoma, and the postoperative&#xD;
               pathology confirmed nonglioblastoma&#xD;
  &#xD;
            -  The patient has other underlying medical conditions that affect survival time&#xD;
  &#xD;
            -  The patient had other underlying medical conditions that affected follow-up or quality&#xD;
               of life assessment&#xD;
  &#xD;
            -  Patients do not have the above exclusion criteria and refuse to participate in&#xD;
               clinical trials after informed consent&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Nu Zhang, Professor</last_name>
      <role>Principal Investigator</role>
      <affiliation>First Affiliated Hospital, Sun Yat-Sen University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Nu Zhang, Professor</last_name>
      <phone>13825070717</phone>
      <email>zhangnu2@mail.sysu.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Kejun He, Attending</last_name>
      <phone>15920463410</phone>
      <email>mailto:hekejun3@ms.sysu.edu.cn</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 7, 2023</last_update_submitted>
    <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>First Affiliated Hospital, Sun Yat-Sen University</investigator_affiliation>
      <investigator_full_name>Zhang Nu</investigator_full_name>
      <investigator_title>First Affiliated Hospital, Sun Yat-Sen University</investigator_title>
    </responsible_party>
    <keyword>glioblastoma</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Glioblastoma</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/NCT05990556
  org study id: ZNu
  nct id: NCT05990556
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Glioblastoma is the most common primary malignancy of the central nervous system with a very
        poor prognosis. Most of the immunotherapies that have made significant breakthroughs in the
        treatment of other tumors in recent years are unsatisfactory in the application of
        glioblastoma, which is mainly inseparable from the highly inhibitory immune microenvironment
        formed by the latter. Therefore, how to change this "immune desert" and better activate
        immune effector cells to play an anti-tumor effect is currently a hot spot in glioma immune
        research. In recent years, there has been continuous research support that the myeloid cells
        of the central nervous system are partly derived from the bone marrow of the skull, and there
        is a special channel connection between the skull and the dura mater, through which immune
        cells can be transported. This suggests that some of the tumor-associated macrophages
        recruited in the glioblastoma microenvironment may be passed through the dura mater. In
        previous animal experiments, we blocked the main blood supply to the dura mater by ligating
        the bilateral external carotid arteries of mice, cutting off the potential supply of dura
        mater to suppressor myeloid cells in the lesion. The results showed that after ligation of
        bilateral external carotid arteries, the survival period of tumor-forming mice was
        significantly prolonged and the prognosis was improved. The proportion of myeloid cells in
        the tumor microenvironment of mice decreased significantly, and the expression of tumor
        suppressor molecules such as arginase Arg1 decreased, indicating that the improvement of
        mouse prognosis was closely related to the proportion and phenotypic changes of myeloid cells
        after dural blood supply blockade. The meningeal lymphatic system of the human central
        nervous system has been shown to be an important part of the immune system, while the
        external carotid artery system, the main source of blood supply to the dura, carries abundant
        immune cells that ooze out to the dura mater through the endothelial window hole of the dural
        blood vessel, which is an important source of dural immune cells. In the glioblastoma immune
        microenvironment, the source of immune cells includes dural branches from the external
        carotid artery system in addition to branches of the internal carotid artery system.
        Therefore, for patients diagnosed with glioblastoma, this study involves embolization of the
        dural branch of the external carotid artery system (bilateral middle meningeal artery) to
        block the dural blood supply before craniotomy. At the same time, microsurgery under
        multimodal image navigation was used to remove the tumor. It is expected to be effective in
        reducing the proportion of myeloid suppressor cells in the tumor microenvironment, slowing
        the growth rate of residual tumor cells, and prolonging the tumor-free progression and
        survival of patients.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Interventional single-arm studies, no grouping.
  1 Randomize groupings 1.1 Method for generating random sequence assignments This study is a real-world study, it is planned to include 20 patients as a case, there is no need for random sequence and blinded allocation before intervention, the patient's condition, experimental purpose, experimental method and possible risks are informed before surgery, and the patient chooses whether to undergo preoperative interventional surgery to block bilateral meningeal blood supply.
  1.2 Randomly assigned hiding This is a real-world study that intends to include three patients as individual cases without random sequencing prior to intervention and therefore does not involve allocation concealment.
  primary purpose: Treatment
  masking: None (Open Label)
  masking description: Blinding and unblinding This is a real-world study that intends to include three patients as case studies without blinding prior to intervention and therefore does not involve blinding.
  measure: Patient survival period
  time frame: 15 months
  description: The overall survival of enrolled patients was compared with the overall survival reported in the literature
  measure: Postoperative recurring time
  time frame: 3-6 months
  description: The Postoperative recurring time in enrolled patients was compared with the mean time in the literature
  arm group label: interventional procedure to block bilateral meningeal blood supply
  arm group type: Experimental
  intervention type: Procedure
  intervention name: interventional procedure to block bilateral meningeal blood supply
  description: The embolic agent used in bilateral meningeal blood supply occlusion through interventional surgery is Onyx glue ("liquid embolic system"). After the location of bilateral middle meningeal artery was determined by femoral artery puncture angiography, SL-10 was sent to the opening of bilateral middle meningeal artery through guiding catheter, and Onxy glue was used to block the bilateral middle meningeal artery. The standard of embolization was that the middle meningeal artery was not seen and Onyx glue was not diffused to the petrous branch of the middle meningeal artery. In order to avoid dangerous anastomotic branches and complications, attention should be paid to superselecting the middle meningeal artery and slowly injecting Onyx glue during the operation. After embolization of the middle meningeal artery by interventional surgery, glioblastoma was removed immediately under the guidance of multimodal imaging.
  arm group label: interventional procedure to block bilateral meningeal blood supply
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Nu Zhang, Professor
  role: Principal Investigator
  affiliation: First Affiliated Hospital, Sun Yat-Sen University
  last name: Nu Zhang, Professor
  phone: 13825070717
  email: zhangnu2@mail.sysu.edu.cn
  last name: Kejun He, Attending
  phone: 15920463410
  email: mailto:hekejun3@ms.sysu.edu.cn
  responsible party type: Sponsor-Investigator
  investigator affiliation: First Affiliated Hospital, Sun Yat-Sen University
  investigator full name: Zhang Nu
  investigator title: First Affiliated Hospital, Sun Yat-Sen University
  mesh term: Glioblastoma