Specific Model Electroacupuncture Stimulation Promotes Paclitaxel Delivery Across the BBB for Postoperative Glioma Patients: A Randomized Controlled Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Overall survival（OS）
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed high-grade glioma, with standard radiotherapy and chemotherapy post-surgical resection deemed unsuccessful, and recurrence confirmed by imaging.
- •Age ≥18 and ≤70 years, open to all genders.
- •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.
- •A Karnofsky Performance Score (KPS) ≥70 or a World Health Organization (WHO) performance status of ≤
- •Meets the criteria for acupuncture, with no severe complications, able to undergo acupuncture treatment and demonstrates good compliance.
- •Clear consciousness, with the ability to perceive and distinguish pain, and capable of basic communication.
- •Signed informed consent, voluntarily participating in this study.
排除标准
- •Uncontrolled epileptic seizures;
- •Peripheral neuropathy > Grade 1;
- •Currently participating in another clinical trial or having participated in a clinical trial that concluded less than 3 months ago;
- •Previous treatment with paclitaxel or similar chemotherapeutic or biologic agents, or history of allergic reactions to these compounds;
- •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);
- •Pregnant or breastfeeding women;
- •Individuals with cognitive impairments such as congenital dementia, or with histories of alcohol, drug, or psychotropic substance abuse;
- •Individuals with a history of needle fainting or infections at the site of acupuncture;
- •Patients with conductive foreign bodies within the body;
- •Individuals unable to undergo enhanced MRI examinations.
研究组 & 干预措施
TMZ group
Temozolomide（TMZ） was given orally or intravenously 150mg/(m2·d) for 5 days, repeated every 28 days for 6 cycles
干预措施: Temozolomide（TMZ） injection or oral administration (Drug)
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).
干预措施: Temozolomide（TMZ） injection or oral administration (Drug)
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).
干预措施: Albumin-Bound Paclitaxel(ABX) intravenous drip (Drug)
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).
干预措施: Specific mode electroacupuncture stimulation(SMES) intervention (Device)
结局指标
主要结局
Overall survival（OS）
时间窗: 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).
次要结局
- Progression-Free Survival (PFS)(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)(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)(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)(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)(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)(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.)
研究者
Xianming Lin
Clinical Professor
The Third Affiliated hospital of Zhejiang Chinese Medical University