Evaluation of Clinical Efficacy and Safety of Specific Mode Electroacupuncture Stimulation for Paclitaxel Across BBB Delivery in Patients With Postoperative Recurrence of Malignant Glioma: A Single-arm Trial

Gliomas are the most common type of primary brain tumors, with the main treatment modalities including surgery, radiotherapy, and chemotherapy. However, gliomas are highly prone to recurrence, posing significant treatment challenges, especially for high-grade gliomas, which have a 5-year survival rate of only 5.5%. Paclitaxel (PTX) is a common chemotherapeutic agent, and its in vitro antitumor efficacy is 1400 times stronger than that of temozolomide (the first-line chemotherapy drug for gliomas). However, due to its large molecular weight (approximately 893 Da), it cannot cross the blood-brain barrier (BBB), preventing its use as a first-line treatment for gliomas. Preliminary research by our team has demonstrated that Specific Mode Electroacupuncture Stimulation (SMES) can open the BBB, increasing the concentration of PTX in tumor tissues, peritumoral tissues, and surrounding invasive tissues, thereby exerting antitumor effects. Therefore, this study aims to preliminarily observe the safety and efficacy of SMES combined with PTX in treating patients with postoperative recurrent high-grade gliomas.

Study Overview

• Status: Recruiting
• Conditions: Glioma
• Intervention / Treatment: Other: SMES+PTX; Drug: Paclitaxel; Device: Specific mode electroacupuncture stimulation

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhaoxing Jia, PHD; Phone Number: +86-18356130598; Email: zhenxinzhenyi183@163.com
• Study Contact Backup: Name: Xianming Lin PHD; Phone Number: +86-13858028101; Email: linxianming1966@163.com

Study Locations

• China
  • Hangzhou City, Zhejiang Province
    • China, Hangzhou City, Zhejiang Province, China, 310000
      • Recruiting
      • The Third Affiliated hospital of Zhejiang Chinese Medical University
      • Contact: Zhaoxing Jia; Phone Number: +8618356130598; Email: zhenxinzhenyi183@163.com
      • Contact: Jia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. WHO grade IV glioma as defined in the "Integrated Diagnosis and Treatment Guidelines for Glioma of the Chinese Anti-Cancer Association" (V2.0_2025 (20250110)).
2. Recurrence confirmed by cranial MRI after surgical resection.
3. According to the Response Assessment in Neuro-Oncology Criteria, version 2.0 (RANO 2.0) standards, there is at least one measurable lesion.
4. Age ≥ 18 years and ≤ 70 years, gender not limited.
5. If dexamethasone is used due to the space-occupying effect, the stable daily dose within 7 days before enrollment should be < 6 mg; if the dose of dexamethasone is being reduced, the average daily dose within 7 days before enrollment should be < 6 mg. Patients receiving dexamethasone treatment for reasons other than the space-occupying effect can still be enrolled.
6. Karnofsky Performance Status Score (KPS) ≥ 40 points or World Health Organization (WHO) Performance Status Score ≤ 3 points.
7. Good bone marrow function, liver and kidney function (within 14 days before treatment): a. Hemoglobin ≥ 90.0 g/L; b. White blood cells ≥ 3.0*10^9/L; c. Absolute neutrophil count ≥ 1500/µL (white blood cell count * neutrophil percentage); d. Platelets ≥ 100*10^9/µl; e. Total bilirubin (TbIL) ≤ 5.0 x ULN; f. Serum aspartate aminotransferase (SGOT) ≤ 3 x ULN and TbIL ≤ 3.0 x ULN; g. Creatinine ≤ 1.5 mg/dL, estimated glomerular filtration rate ≥ 30 mL/min to < 90 mL/min)
8. Able to receive electroacupuncture treatment and have good compliance.
9. Clear consciousness, pain perception and discrimination ability, and basic communication ability.
10. Signed the informed consent form and voluntarily participated in this study.

Exclusion criteria

1. Seizure attack, uncontrollable.
2. Those who are currently participating in other clinical trials or have completed other clinical trials within less than one month.
3. Those who have received treatment containing paclitaxel or similar drugs.
4. Those who have a severe allergy to paclitaxel or similar substances.
5. Pregnant or lactating women.
6. Those with diseases affecting cognitive function such as congenital dementia, or alcoholics, drug addicts or those with abuse of psychotropic substances.
7. Those with infected skin at the acupuncture site.
8. Patients with metallic foreign bodies in their bodies.
9. Those who cannot undergo cranial enhanced MRI examination.
10. Other acute or chronic diseases, mental disorders or abnormal laboratory test values that may increase the risk associated with participating in the study or the administration of the study drug, or interfere with the interpretation of study results, and the investigator determines that the patient does not meet the eligibility criteria for participation in the study.
11. Those who are undergoing other types of anti-tumor treatments simultaneously during the trial, such as chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment group; Patients in the treatment group received both paclitaxel(PTX) and a specific mode electroacupuncture stimulation（SMES） . Drug: Paclitaxel is administered intravenously at a dose of 135-175mg/m², repeated every 3 weeks. Device: SMES immediately after the ABX intravenous infusion began, the patient was placed in a supine position, the skin was routinely disinfected with 75% ethanol, and a stainless steel needle was inserted into GV20 and GV26.Then, the needles are stimulated by using an acupuncture point nerve stimulator with a frequency of 2/100 Hz and an intensity of 3 mA for 40 min (a homemade relay cycled power to the electrode for 6 sec on and 6 sec off).

Other: SMES+PTX; This intervention involves the combined use of medication and device, where the specific mode electroacupuncture stimulation (SMES) intervention is administered simultaneously with the intravenous infusion of paclitaxel.; Drug: Paclitaxel; Paclitaxel is administered intravenously at a dose of 135-175mg/m², repeated every 3 weeks.; Device: Specific mode electroacupuncture stimulation; Patients assume a supine position. After routine skin disinfection with 75% ethanol, a stainless steel needle (size 0.25mm×40mm) is inserted into GV20 (Baihui), and another stainless steel needle (size 0.25mm×25mm, as described above) is inserted into GV26 (Shuigou). The acupoints are manually stimulated until the patient experiences soreness, distension, or heaviness (the "De Qi" response). Subsequently, the needles are stimulated using an acupuncture point nerve stimulator (HANS-200, Nanjing Jinsheng Ltd., China) at a frequency of 2/100 Hz and an intensity of 3 mA for 40 minutes (a homemade relay cycled power supply to the electrode, with 6 seconds on and 6 seconds off). The intervention is administered every three weeks, concurrently with paclitaxel treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
4-month progression-free survival rate	Comprehensive neurological examinations and MRI scans were performed at baseline to establish the initial disease status. These assessments were repeated at specified post-treatment time points (weeks 3, 6, 9, 12, 15, and 18) to evaluate changes compared to baseline. Responses, including complete response , partial response, stable disease , and progressive disease, were assessed according to the specific criteria outlined in the RANO 2.0 guidelines.Finally, the proportion of subjects in the intent-to-treat population with progression-free survival exceeding 4 months was calculated.	baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30	The questionnaire consists of 30 items and covers multiple dimensions, such as physical function, role function, emotional function, social function, quality of life, fatigue, pain, and other cancer-related symptoms.	baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.
The Neurological Assessment for Neuro-Oncology (NANO)	NANO Scale quantitatively assesses nine neurological functions in patients, including gait, muscle strength, sensation, visual fields, facial strength, speech, cognition, and limb coordination, with each category scored between 0 to 3 or 0 to 2.	baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.
Overall survival(OS)	The time from enrollment to death for any reason (for lost-to-follow-up patients, the time of the last follow-up; for patients still alive at the end of the study, the time of the last follow-up).	On the last day of weeks 3, 6, 9, 12, 15, and 18 during the treatment period; and then monthly during the follow-up phase for a total of 12 times.
Disease control rate	Disease control rate refers to the proportion of patients in the intent-to-treat population who achieved complete response , partial response , or stable disease , as assessed by the RANO 2.0 criteria.	baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.
Objective response rate	Objective response rate refers to the proportion of patients in the intent-to-treat population who achieved complete response or partial response , as assessed per the RANO 2.0 criteria.	baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18.
Progression-free survival	Progression-free survival was defined as the time interval from the initiation of SMES combined with ABX treatment until the first occurrence of any of the following events: radiographic disease progression as determined by Response Assessment in Neuro-Oncology (RANO) version 2.0 criteria, the development of intolerable treatment-related adverse events leading to treatment discontinuation, or death due to any cause.	On the last day of weeks 3, 6, 9, 12, 15, and 18 during the treatment period; and then monthly during the follow-up phase for a total of 12 times.
Duration of response	Duration of response was defined as the time interval between the first administration of SMES plus ABX therapy and the occurrence of disease progression.	baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18
Duration of Disease Control	Duration of Disease Control was defined as the time interval from when a patient first achieved disease control (complete response , partial response , or stable disease until disease progression or death, whichever occurred first.	baseline and 1-2 days before the end of weeks 3, 6, 9, 12, 15, and 18
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	Adverse reactions were recorded from the time of informed consent signing through the final visit, including any emerging symptoms, signs, and laboratory abnormalities. Common adverse reactions may include skin discomfort, pruritus, pain, etc., with severity graded into 5 levels.	On the 7th, 14th and 21st days of the 1st to 6th treatment cycles, each treatment cycle lasts for 21 days.

Collaborators and Investigators

• Sponsor: The Third Affiliated hospital of Zhejiang Chinese Medical University

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2025
• Primary Completion (Estimated): February 24, 2028
• Study Completion (Estimated): February 24, 2028

Study Registration Dates

• First Submitted: February 5, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): February 10, 2025

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 29, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: glioma; Paclitaxel; blood-brain barrier; Specific Mode Electroacupuncture Stimulation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Recurrence; Glioma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: ZSLL-KY-2024-079-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data and results of this study need to be confirmed by Lin Xianming

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No