Effect of Electroacupuncture Combined With Paclitaxel Clinical Efficacy of Patients With Recurrence of High-grade Glioma

March 19, 2024 updated by: Xianming Lin, The Third Affiliated hospital of Zhejiang Chinese Medical University

Specific Model Electroacupuncture Stimulation Promotes Paclitaxel Delivery Across the BBB for Postoperative Glioma Patients: A Randomized Controlled Study

Gliomas are the most common type of primary brain tumors, with surgery followed by radiotherapy and chemotherapy as the main treatment modalities. However, they are highly prone to recurrence, presenting significant treatment challenges, especially for high-grade gliomas, which have a 5-year survival rate of only 5.5%. Paclitaxel, a common chemotherapeutic agent, exhibits antitumor effects in vitro that are 1400 times stronger than those 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, precluding 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 blood-brain barrier, enhancing the concentration of albumin-bound paclitaxel (ABX) in tumor tissues, peritumoral tissues, and surrounding invasive tissues, thereby exerting antitumor effects. Consequently, this study aims to observe the safety and efficacy of SMES combined with ABX in treating patients with recurrent high-grade gliomas postoperatively, to explore its mechanisms of action, extend survival, improve quality of life, and forge new theories and methods for the integrative treatment of brain tumors combining traditional Chinese and Western medicine.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

58

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Zhejiang, China
        • Recruiting
        • the Third Affiliated Hospital of Zhejiang Chinese Medical University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically confirmed high-grade glioma, with standard radiotherapy and chemotherapy post-surgical resection deemed unsuccessful, and recurrence confirmed by imaging.
  2. Age ≥18 and ≤70 years, open to all genders.
  3. If receiving dexamethasone for mass effect, a stable daily dose of <6 mg in the 7 days prior to enrollment, or if the dose of dexamethasone is decreasing, an average daily dose of <6 mg in the 7 days prior to enrollment. Patients receiving dexamethasone for reasons other than mass effect are still eligible.
  4. A Karnofsky Performance Score (KPS) ≥70 or a World Health Organization (WHO) performance status of ≤2.
  5. Meets the criteria for acupuncture, with no severe complications, able to undergo acupuncture treatment and demonstrates good compliance.
  6. Clear consciousness, with the ability to perceive and distinguish pain, and capable of basic communication.
  7. Signed informed consent, voluntarily participating in this study.

Exclusion Criteria:

  1. Uncontrolled epileptic seizures;
  2. Peripheral neuropathy > Grade 1;
  3. Currently participating in another clinical trial or having participated in a clinical trial that concluded less than 3 months ago;
  4. Previous treatment with paclitaxel or similar chemotherapeutic or biologic agents, or history of allergic reactions to these compounds;
  5. Patients with severe cardiac, hepatic, renal, or hematologic dysfunction (criteria within 14 days prior to treatment include: a. Hemoglobin ≥ 90.0 g/L; b. White blood cells ≥ 3.010^9/L; c. Absolute neutrophil count ≥ 1500/µL; d. Platelets ≥ 10010^9/µL; e. Total bilirubin (TbIL) ≤5.0 x ULN; f. Serum aspartate aminotransferase (SGOT) ≤10 x ULN and TbIL >3 to ≤5.0 x ULN; g. Creatinine ≤1.5 mg/dL, estimated creatinine clearance ≥ 30 mL/min to <90 mL/min);
  6. Pregnant or breastfeeding women;
  7. Individuals with cognitive impairments such as congenital dementia, or with histories of alcohol, drug, or psychotropic substance abuse;
  8. Individuals with a history of needle fainting or infections at the site of acupuncture;
  9. Patients with conductive foreign bodies within the body;
  10. Individuals unable to undergo enhanced MRI examinations.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: TMZ group
Temozolomide（TMZ） was given orally or intravenously 150mg/(m2·d) for 5 days, repeated every 28 days for 6 cycles
Drug: Temozolomide（TMZ） injection or oral administration
Oral administration of TMZ150-200mg/m2/ day, continuous use for 5 days, discontinued for 23 days, for a treatment cycle, a total of 6 cycles.
Other: SMES+ABX+TMZ Group

Drug:

Oral or intravenous infusion of TMZ 150mg/(m2·d) for 5 days, repeated after 23 days of suspension, a total of 6 treatment cycles. During the TMZ treatment cycle, specific mode electroacupuncture stimulation（SMES） combined with Paclitaxel for Injection (Albumin Bound)（ABX） were used on day 1 and day 8.

ABX： ABX was prepared with 0.9% sodium chloride injection and the dosage required by the patient was calculated at 110mg/mm2. Then the intravenous infusion continues for 30 minutes.

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).
Drug: Temozolomide（TMZ） injection or oral administration
Oral administration of TMZ150-200mg/m2/ day, continuous use for 5 days, discontinued for 23 days, for a treatment cycle, a total of 6 cycles.
Drug: Albumin-Bound Paclitaxel(ABX) intravenous drip
ABX was administered intravenously at a dose of 110mg/m2 on days 1 and 8 of a 28-day treatment cycle
Device: Specific mode electroacupuncture stimulation(SMES) intervention
Patients take supine position. After skin disinfection with 75% ethanol routine disinfection, the stainless needle (size 0.25mm×40mm, Hua Tuo brand, Suzhou Medical Supplies Company Ltd in Jiangsu, China) will be inserted in GV20（Baihui) and the stainless needle(size 0.25mm×25mm, described above) will be inserted in GV26 (Shuigou), acupoints will be stimulated manually until patients feel soreness, distension or heaviness (the reaction of "De Qi"). Then, the needles are stimulated by using an acupuncture point nerve stimulator (HANS-200, Nanjing Jinsheng, Ltd., China) 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).The 28-day treatment cycle was followed by simultaneous intervention with ABX on days 1 and 8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival（OS）
Time Frame: Starting from randomization, during the follow-up phase, telephone follow-ups to record survival status are conducted every two months, totaling six follow-ups. This structured approach ensures a comprehensive assessment of patient out
The duration from randomization to death due to any cause is measured (for patients lost to follow-up, the last follow-up date is used; for patients alive at the end of the study, the date of the last follow-up is considered).
Starting from randomization, during the follow-up phase, telephone follow-ups to record survival status are conducted every two months, totaling six follow-ups. This structured approach ensures a comprehensive assessment of patient out

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Up to 12 months were assessed from the date of randomization to the date of first recording to the date of progression or the date of death from any cause, whichever came first
The period from randomization to the first occurrence of tumor progression or death is meticulously monitored.
Up to 12 months were assessed from the date of randomization to the date of first recording to the date of progression or the date of death from any cause, whichever came first
Head MRI (plain and enhanced)
Time Frame: One treatment cycle is 28 days, with cranial MRI scans conducted one day before the start of treatment cycles 1, 3, and 5, and at the end of treatment cycle 6.
The short-term efficacy of the two groups is analyzed, referencing the RANO criteria for assessing the efficacy of solid tumor treatment before and after therapy. Complete Response (CR) is when visible tumor lesions disappear completely, maintained for >4 weeks (in accordance with RANO criteria and RECIST version 2000). Partial Response (PR) involves a reduction of ≥50% in the sum of the diameters of the tumor lesions, with no increase in other lesions and no new lesions appearing, maintained for >4 weeks. Stable Disease (SD) is defined as the sum of the diameters of the tumor lesions decreasing by <50% or increasing by ≤25%, with no new lesions appearing, maintained for >4 weeks. Progression (PD) occurs when there is an increase of >25% in the sum
One treatment cycle is 28 days, with cranial MRI scans conducted one day before the start of treatment cycles 1, 3, and 5, and at the end of treatment cycle 6.
he Karnofsky Performance Score (KPS)
Time Frame: One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.
KPS ranges from 0 to 100, with scores directly correlating to quality of life.
One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.
The Eastern Cooperative Oncology Group (ECOG)
Time Frame: One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.
ECOG Performance Status is scored from 0 to 5, with scores inversely related to quality of life.
One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.
The Quality of Life (QOL)
Time Frame: One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.
QOL scale for cancer patients assesses quality of life, with a total score ranging from 0 to 60, where scores directly correlate with quality of life.
One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.
The Neurological Assessment for Neuro-Oncology (NANO)
Time Frame: One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.
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.
One treatment cycle is 28 days, with assessments conducted one day before the start of treatment cycles 1 through 6 and one day before the end of treatment cycle 6.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Third Affiliated hospital of Zhejiang Chinese Medical University

Collaborators

Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

February 26, 2024

First Submitted That Met QC Criteria

March 19, 2024

First Posted (Actual)

March 26, 2024

Study Record Updates

Last Update Posted (Actual)

March 26, 2024

Last Update Submitted That Met QC Criteria

March 19, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZSLL-KY-2024-010-01

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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