Esketamine in Microelectrode Recording-guided Subthalamic Deep-Brain Stimulation for Parkinson's Disease

Official title

Esketamine in Microelectrode Recording-guided Subthalamic Deep-Brain Stimulation for Parkinson's Disease（ASPIRE）：A Randomized Controlled, Double-blind Study

Overview

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.

Detailed description

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.

Interventions

• Drug esketamine
  After the craniotomy, a continuous infusion of ketamine at a rate of 0.3 mg/kg/h (0.3 ml/kg/h) is administered until the completion of electrode implantation, prior to microelectrode recording (MER) and electrode insertion. After the administration of the drug, close monitoring of the patient's blood pressure and heart rate is conducted to maintain circulatory stability.
• Drug normal Saline
  After the craniotomy, a continuous infusion of normal saline at a rate of 0.3 ml/kg/h is administered until the completion of electrode implantation, prior to microelectrode recording (MER) and electrode insertion. After the administration of the drug, close monitoring of the patient's blood pressure and heart rate is conducted to maintain circulatory stability.

Primary outcome measures

• NRMS [Time frame: 1 day (during MER recording)]

Secondary outcome measures (8)

• Beta band (13-30 Hz) oscillations calculated by spectrum analysis [Time frame: 1 day (during MER recording)]
• Early postoperative Quality of sleep [Time frame: the first and the second and the third day after surgery]
• Long-term Quality of sleep [Time frame: before surgery and the 30days after surgery]
• Anxiety [Time frame: before surgery and the 30days after surgery]
• Depression [Time frame: before surgery and the 30days after surgery]
• Delirium Assessment: 3-Minute Diagnostic Interview for CAM (3D-CAM) [Time frame: Postoperative 3 days and the 30th day]
• The incidence of anaesthesia-related adverse events [Time frame: 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 [Time frame: 24 hours after operation for surgical experience satisfaction and 1 months after STN-DBS for DBS satisfaction]

Eligibility criteria

Inclusion criteria

1.50-80 years old, ASA grade II-III; 2.Bilateral STN-DBS of patients with Parkinson's disease; 3.Signed informed consent.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT06543563 · dn20231202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗