Esketamine in Microelectrode Recording-guided Subthalamic Deep-Brain Stimulation for Parkinson's Disease（ASPIRE）：A Randomized Controlled, Double-blind Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 102
- 试验地点
- 1
- 主要终点
- NRMS
研究概览
简要总结
Under regional anesthesia, subthalamic nucleus deep brain stimulation (STN-DBS) has proven to be an effective therapeutic approach for improving motor symptoms in Parkinson's disease. However, a significant portion of Parkinson's disease (PD) patients is unable to cooperate with the surgery, necessitating the use of awake sedation. Nevertheless, the administration of anesthetic drugs often impacts the electrical signals recorded by microelectrodes to varying degrees. This study is designed as a prospective, randomized, placebo-controlled, double-blind, two-arm investigation. PD patients scheduled for bilateral STN-DBS surgery will be randomly assigned to either the Dexmedetomidine group or the Dexmedetomidine combined with Esketamine group. The differences in neural activity between the two groups will be assessed using the normalized root mean square (NRMS) method. The primary outcome measure is NRMS, while secondary outcome measures include differences in beta oscillation power spectrum analysis, postoperative delirium incidence, postoperative changes in sleep disturbances, postoperative depression, anxiety status, and occurrence of adverse events.
详细描述
Regional anesthesia for subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment method for improving motor symptoms in Parkinson's disease. However, the majority of Parkinson's disease (PD) patients require awake sedation during the procedure. Nevertheless, the administration of anesthetic drugs often impacts the microelectrode recording (MER) signals to varying degrees. Current research suggests that Esketamine can provide sedation and analgesia while preserving the active brain electrical signals of patients. Additionally, it has been shown to improve sleep disturbances and alleviate depression and anxiety in patients.This study aims to compare the impact of Dexmedetomidine alone and Dexmedetomidine combined with Esketamine on MER during awake sedation in PD patients undergoing STN-DBS surgery, to clarify the influence of Esketamine on the intraoperative electrical signals of PD patients under awake sedation during DBS surgery. The experiment is designed as a prospective, randomized, placebo-controlled, non-inferiority study with a double-blind, two-arm design. PD patients scheduled for bilateral STN-DBS surgery will be randomly assigned to either the Dexmedetomidine group or the Dexmedetomidine combined with Esketamine group. The differences in neural activity between the two groups will be assessed using the normalized root mean square (NRMS) method. The primary outcome measure is NRMS, while secondary outcome measures include differences in beta oscillation power spectrum analysis, postoperative delirium incidence, postoperative changes in sleep disturbances, postoperative depression, anxiety status, and occurrence of adverse events.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.50-80 years old, ASA grade II-III; 2.Bilateral STN-DBS of patients with Parkinson's disease; 3.Signed informed consent.
排除标准
- •Obstructive sleep apnea;
- •BMI > 30kg/m2;
- •Estimated difficult airway;
- •Severe preoperative anxiety;
- •Serious dysfunction of important organs (i.e. heart failure, renal or liver dysfunction)
- •A history of allergy to the anaesthetics.
研究组 & 干预措施
DEX
A loading dose of DEX 0.3 µg/kg was infused intravenously at a constant speed within 10 min after the patients entered the operating room, and the DEX maintenance dose was infused at 0.3µg/kg/h until the end of the first stage (deep-brain stimulation implantation) of the operation. After the craniotomy, normal saline is infused at a rate of 3 ml/kg/h until the completion of electrode implantation, prior to microelectrode recording (MER) and electrode insertion. Blood pressure and heart rate of the patient are closely monitored after drug administration to maintain circulatory stability.
干预措施: normal Saline (Drug)
DEX-KET
A loading dose of DEX 0.3 µg/kg was infused intravenously at a constant speed within 10 min after the patients entered the operating room, and the DEX maintenance dose was infused at 0.3µg/kg/h until the end of the first stage (deep-brain stimulation implantation) of the operation. After the craniotomy, esketamine (0.1mg/ml) is infused at a rate of 3ml/kg/h until the completion of electrode implantation, prior to microelectrode recording (MER) and electrode insertion. Blood pressure and heart rate of the patient are closely monitored after drug administration to maintain circulatory stability.
干预措施: esketamine (Drug)
结局指标
主要结局
NRMS
时间窗: 1 day (during MER recording)
The investigators will use the root mean square (RMS) value of the MER sampled signal as the main parameter for evaluating electrode position. RMS values change with the electrode properties and other external drives related to the operating room; therefore, it is crucial to normalize the RMS to comparable values. Thus, each session's RMS in a trajectory is divided by the mean RMS of the first five stable sessions in the same trajectory. This normalized RMS (NRMS) is found to be a good measure as it reflects the relative change in the total power of the signal, which elevates dramatically entering the STN.
次要结局
- Early postoperative Quality of sleep(the first and the second and the third day after surgery)
- Beta band (13-30 Hz) oscillations calculated by spectrum analysis(1 day (during MER recording))
- Long-term Quality of sleep(before surgery and the 30days after surgery)
- Anxiety(before surgery and the 30days after surgery)
- Delirium Assessment: 3-Minute Diagnostic Interview for CAM (3D-CAM)(Postoperative 3 days and the 30th day)
- The incidence of anaesthesia-related adverse events(Up to 3 days after randomization])
- Depression(before surgery and the 30days after surgery)
- Surgical experience satisfaction 24 hours after the operation and DBS satisfaction 1 months after the operationevaluated by the seven-point Likert scale(24 hours after operation for surgical experience satisfaction and 1 months after STN-DBS for DBS satisfaction)
研究者
Ruquan Han
Director of Anesthesiology Department
Beijing Tiantan Hospital