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

August 4, 2024 updated by: Ruquan Han, Beijing Tiantan Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100070
        • Recruiting
        • Beijing Tiantan Hospital, Capital Medical University
        • Contact:
        • Principal Investigator:
          • Ruquan Han, MD,PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: 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.
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.
Experimental: 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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
NRMS
Time Frame: 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.
1 day (during MER recording)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Beta band (13-30 Hz) oscillations calculated by spectrum analysis
Time Frame: 1 day (during MER recording)
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
Time Frame: the first and the second and the third day after surgery
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
Time Frame: before surgery and the 30days after surgery
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
Time Frame: before surgery and the 30days after surgery
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
Time Frame: before surgery and the 30days after surgery
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)
Time Frame: Postoperative 3 days and the 30th day
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
Time Frame: Up to 3 days after randomization]
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
Time Frame: 24 hours after operation for surgical experience satisfaction and 1 months after STN-DBS for DBS satisfaction
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Beijing Tiantan Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ruquan Han, MD,PhD, study principal investigator

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 9, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 22, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 9, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 9, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 4, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • dn20231202

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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