Research on the Safety and Efficacy of Blocking Dural Blood Supply in Glioblastoma Patients

Sponsor

Zhang Nu (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05990556

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Meningeal Arteries	Procedure: interventional procedure to block bilateral meningeal blood supply	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

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.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.

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.

Primary Purpose:

Treatment

Official Title:

Research on the Safety and Efficacy of Blocking Dural Blood Supply in Glioblastoma Patients

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: interventional procedure to block bilateral meningeal blood supply	Procedure: interventional procedure to block bilateral meningeal blood supply 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

Intervention/Treatment

Experimental: interventional procedure to block bilateral meningeal blood supply

Procedure: interventional procedure to block bilateral meningeal blood supply

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.

Outcome Measures

Primary Outcome Measures

Patient survival period [15 months]
The overall survival of enrolled patients was compared with the overall survival reported in the literature

Secondary Outcome Measures

Postoperative recurring time [3-6 months]
The Postoperative recurring time in enrolled patients was compared with the mean time in the literature

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Imaging or needle biopsy pathologically diagnosed as glioblastoma
Patients have not previously received radiotherapy, chemotherapy and other treatment modalities for intracranial lesions
There are no related contraindications such as neurovascular intervention and craniotomy

Exclusion Criteria:

The patient's initial imaging diagnosis was glioblastoma, and the postoperative pathology confirmed nonglioblastoma
The patient has other underlying medical conditions that affect survival time
The patient had other underlying medical conditions that affected follow-up or quality of life assessment
Patients do not have the above exclusion criteria and refuse to participate in clinical trials after informed consent

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Zhang Nu

Investigators

Principal Investigator: Nu Zhang, Professor, First Affiliated Hospital, Sun Yat-Sen University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Zhang Nu, First Affiliated Hospital, Sun Yat-Sen University, First Affiliated Hospital, Sun Yat-Sen University

ClinicalTrials.gov Identifier:

NCT05990556

Other Study ID Numbers:

First Posted:

Aug 14, 2023

Last Update Posted:

Aug 14, 2023

Last Verified:

Aug 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Zhang Nu, First Affiliated Hospital, Sun Yat-Sen University, First Affiliated Hospital, Sun Yat-Sen University

glioblastoma

Additional relevant MeSH terms:

Glioblastoma

Study Results

No Results Posted as of Aug 14, 2023