Esketamine in Microelectrode Recording-guided Subthalamic Deep-Brain Stimulation for Parkinson's Disease
NCT Number: NCT06543563
Acronym: ASPIRE
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: PD - Parkinson's Disease|Deep Brain Stimulation|Esketamine
Interventions: DRUG: esketamine|DRUG: normal Saline
Sponsor: Beijing Tiantan Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 102
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-09
Completion Date: 2026-01-31
Locations: Beijing Tiantan Hospital, Capital Medical University, Beijing, Beijing, 100070, China

Summary:
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.

Primary Outcome Measures: NRMS, 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., 1 day (during MER recording)
Secondary Outcome Measures: Beta band (13-30 Hz) oscillations calculated by spectrum analysis, Power spectrum will be calculated using a discrete Fourier transform of the sampling windows to allow evaluation of change in oscillatory activity along time. Synchronized beta band (13-30 Hz) oscillations are often observed in the dorsolateral region of the STN of PD patients and are thought to play a role in the disease pathophysiology. The power of beta band will be calculated by averaging the power across the corresponding frequency band., 1 day (during MER recording)|Early postoperative Quality of sleep, The early postoperative sleep quality will be monitored using a portable sleep monitor, with indicators including the duration of total sleep, the proportion of light sleep, deep sleep, and rapid eye movement (REM) sleep., the first and the second and the third day after surgery|Long-term Quality of sleep, Long-term quality of sleep will be evaluated with Pittsburgh Sleep Quality Index (PSQI) ,a score of 0 to 21, the higher score means a worse quality of sleep., before surgery and the 30days after surgery|Anxiety, Anxiety will be evaluated using Hamilton Anxiety Rating Scale (HAMA)，a score of 0 to 56，the higher score means a worse anxiety, before surgery and the 30days after surgery|Depression, Depression will be evaluated using Hamilton Depression Rating Scale (HAMD)，a score of 0 to 76,the higher score means a worse depression, before surgery and the 30days after surgery|Delirium Assessment: 3-Minute Diagnostic Interview for CAM (3D-CAM), Postoperative delirium is assessed by the 3-minute diagnostic interview for CAM(3D-CAM),the score is 0 or 1, where 0 represents non-delirium and 1 represents delirium., Postoperative 3 days and the 30th day|The incidence of anaesthesia-related adverse events, Nausea, vomiting, excessive Secretions and intraoperative awareness, Up to 3 days after randomization]|Surgical experience satisfaction 24 hours after the operation and DBS satisfaction 1 months after the operationevaluated by the seven-point Likert scale, The seven-point Likert scale will be used in the present trial. It is a questionnaire answered by the patient 24 hoursafter the operation. The scale reported the experience of the patient from very dissatisfied to very satisfied, as graded from 1-7., 24 hours after operation for surgical experience satisfaction and 1 months after STN-DBS for DBS satisfaction