Choice of Anesthesia in Microelectrode Recording Guided Deep Brain Stimulation for Parkinson's Disease (CHAMPION)

Choice of Anesthesia in Microelectrode Recording Guided Deep Brain Stimulation for Parkinson's Disease (CHAMPION)：A Randomized Controlled, Non-Inferiority Study

Subthalamic nucleus (STN)-deep brain stimulation (DBS) under general anesthesia has been applied to PD patients who cannot tolerate awake surgery, but general anesthesia will affect the electrical signal in microelectrode recording (MER) to some degree. This study is a prospective randomized controlled, noninferiority study, open label, endpoint outcome evaluator blinded, two-arm study. Parkinson's disease patients undergoing STN-DBS are randomly divided into a conscious sedation group (dexmedetomidine) and a general anesthesia group (desflurane). Normalized root mean square (NRMS) is used to compare the difference of neuronal activity between the two groups. The primary outcome is the percentage of high NRMS recorded by the MER signal (with the average NRMS recorded by MER after entering the STN greater than 2.0). The secondary outcomes are the NRMS, length of the STN, number of MER tracks, and differences in clinical outcomes 6 months after the operation.

Study Overview

• Status: Recruiting
• Conditions: Desflurane; Dexmedetomidine; Deep Brain Stimulation; PD - Parkinson's Disease
• Intervention / Treatment: Drug: general anesthesia; Drug: Conscious sedation

Detailed Description

STN-DBS under general anesthesia has been applied to PD patients who cannot tolerate awake surgery, but general anesthesia will affect the electrical signal in microelectrode recording (MER) to some degree. At present, there are some studies on the effects of desflurane on neuronal signal amplitude and discharge characteristics during STN-DBS in PD patients but there is no definite conclusion.

This study compares the influence of MER mapping during STN-DBS and the differences in postoperative clinical outcomes between desflurane general anesthesia and conscious sedation anesthesia to explore alternative anesthesia for DBS in PD patients who cannot tolerate local anesthesia or conscious sedation and to provide feasible anesthesia techniques for the application of MER during DBS under general anesthesia.

This study is a prospective randomized controlled, noninferiority study, open label, endpoint outcome evaluator blinded, two-arm study. Parkinson's disease patients undergoing STN-DBS are randomly divided into a conscious sedation group (dexmedetomidine) and a general anesthesia group (desflurane). The primary outcome is the percentage of high NRMS recorded by the MER signal (with the average NRMS recorded by MER after entering the STN greater than 2.0), which is used to compare the differences in neuronal electrical activities between conscious sedation and general anesthesia via desflurane groups. The secondary outcomes are the NRMS, length of the subthalamic nucleus, number of MER tracks, and differences in clinical outcomes 6 months after the operation.

• Study Type: Interventional
• Enrollment (Estimated): 188
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ruquan Han, MD, PhD; Phone Number: 8610-59976660; Email: ruquan.han@gmail.com

Study Locations

• China
  • Beijing, China, 100070
    • Recruiting
    • Beijing Tiantan Hospital, Capital Medical University
    • Contact: Ruquan Han, M.D., Ph.D; Phone Number: 8610-59976660; Email: ruquan.han@gmail.com
    • Principal Investigator: Ruquan Han, M.D., Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. Obstructive sleep apnea;
2. BMI > 30kg/m2;
3. Estimated difficult airway;
4. Severe preoperative anxiety;
5. Serious dysfunction of important organs (i.e. heart failure, renal or liver dysfunction)
6. A history of allergy to the anaesthetics.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: General anesthesia	Drug: general anesthesia; The patients did not use any preoperative sedative drugs and were given sufentanil citrate 0.1-0.2 µg/kg, cisatracurium 0.2 mg/kg and propofol 1.5-2.0 mg/kg during anesthesia induction. After the patients were unconscious, oral endotracheal intubation was performed. Anesthesiologists should continuously monitor PetCO2 and maintain PetCO2 at 30-35 mmHg. During the operation, patients are treated with remifentanil, cisatracurium, and desflurane inhalation at 0.5-1.0 minimum alveolar concentration (MAC). In the MER process, the desflurane concentration is adjusted to maintain 0.5-0.6 MAC. If the desflurane concentration needs to be adjusted to less than 0.5 MAC during MER for various reasons, remedial measures will be implemented.
Active Comparator: Conscious sedation	Drug: Conscious sedation; A loading dose of DEX 0.5 µg/kg was infused intravenously at a constant speed within 15 min after the patients entered the operating room, and the DEX maintenance dose was infused at 0.2-0.5 µg/kg/h until the end of the first stage (deep-brain stimulation implantation) of the operation. Maintain the BIS value at 60-80.; Other Names: asleep-awake-asleep anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of high-normalized root mean square (high-NRMS) recorded by the MER signal (with the average NRMS recorded by MER after entering the STN greater than 2.0).	We 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

Outcome Measure	Measure Description	Time Frame
Proportion of intraoperative remedial measures implemented	If the characteristic discharge activity of neurons cannot be recovered after maintaining the target anaesthetic concentration during MER, the following procedures should be implemented: ① Reduce the concentration of anaesthetics for a short time and wait for the recovery of electrical signals; ② Readjust the target position; and ③ If the STN cannot be successfully identified by MER, implant electrodes with preoperative imaging localization.	1 day (during MER recording)
The incidence of operation-related complications	Second operation, infection, intracranial haemorrhage, etc.	Up to 6 months after randomization
NRMS and their stratified proportions in the CS and GA groups	We 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. We will stratify the mean NRMS of the two groups at the level of 0.5, and calculate the stratified proportions.	1 day (during MER recording)
Firing rates	The firing rates will be calculated using customized scripts developed from the Osort toolbox.	1 day (during MER recording)
Lengths of STN(mm)	The STN pass length is determined as the distance from entry to exit of the STN based on the significant, clear increase in baseline unit activity and FR changes unique to STN.	1 day (during MER recording)
Total electrode path times	Total electrode path times are the total number of paths actually selected, which can be used as an indirect indicator to judge the accuracy of positioning.	1 day (during MER recording)
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)
Duration of operation and MER	The operation time and MER recording time from the start to the end.	1 day (during the DBS surgery)
The accuracy of the DBS electrode	The accuracy of the target location is defined by the neurosurgeon's review of the postoperative CT scan.	Within 24 hours after the operation
Clinical efficacy measured with the improvement of the United Parkinson's Disease Rating Scale (UPDRS)-III (conditions: med on/off, stim on/off)	UPDRS -III is the standard test used by movement disorders neurologists to measure balance impairment in PD.	6 months after STN-DBS
Clinical efficacy measured with Levodopa equivalent daily dose (LEDD) reduction	Dopaminergic medication is converted into levodopa equivalent, which is assessed the degree of medication reduction.	6 months after STN-DBS
Cognitive function as measured by the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA)	MMSE and MoCA will be used to assess cognitive function	At baseline and 24 hours, 2 days, 3 days and 6 months after the operation
Quality of life measured with the Parkinson's Disease Quality of Life Questionnaire (PDQ-39)	PDQ-39 will be used to assess changes in the quality of life of the patients.	6 months after STN-DBS
The incidence of anaesthesia-related adverse events	Nausea, vomiting and intraoperative awareness.	Up to 3 days after randomization
Surgical experience satisfaction 24 hours after the operation and DBS satisfaction 6 months after the operation evaluated 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 hours after 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 6 months after STN-DBS for DBS satisfaction

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Ruquan Han, MD, PhD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2022
• Primary Completion (Actual): March 26, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 21, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: xsn20220618

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No