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Deep Brain Stimulation (DBS) Sedation

Effects of Anesthesia Drugs on Neuronal Activity in the Basal Ganglia and Thalamus During Deep Brain Stimulation Electrode Implantation Surgery

Status
Terminated
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03283150
Enrollment
20
Registered
2017-09-14
Start date
2017-12-01
Completion date
2022-01-20
Last updated
2024-07-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Brain, Sedation

Keywords

Deep Brain Stimulation(DBS), Sedation, DBS Implantation, Microelectrode recording(MER)

Brief summary

Deep brain stimulation (DBS) of different brain nuclei is a treatment for multiple brain disorders. The subthalamic nucleus (STN) and globus pallidus have been used to treat advanced Parkinson's disease for a long time. The ventral intermediate nucleus of the thalamus is an effective target for treating essential tremor patients. STN and the internal segment of the globus pallidus are useful targets for treating dystonia. To achieve this optimal electrode localization, many centers perform electrophysiological mapping of the target nuclei using microelectrode recording (MER). This way they can achieve precise localization of the electrode. During the mapping procedure, microelectrodes are passed through the target nuclei, and the electrical neuronal activity is observed and recorded. The surgical team can identify the precise location of the target nuclei and its borders according to the typical activity of its neurons. This study will compare the activity of neurons in several DBS targets before, during and after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the effects of anesthetics on the neuronal activity in these targets, allowing us to choose the most appropriate sedation protocol to use during implantation of DBS electrodes in deep brain structures (bearing in mind that each structure may have a different optimal protocol).

Detailed description

Deep brain stimulation (DBS) of different brain nuclei is evolving as an essential component of the treatment for multiple brain disorders. The subthalamic nucleus (STN) and globus pallidus have been used to treat advanced Parkinson's disease for a long time. The ventral intermediate nucleus of the thalamus is an effective target for treating essential tremor patients. STN and the internal segment of the globus pallidus are useful targets for treating dystonia. Aside from movement disorders DBS has demonstrated efficacy in the treatment of other conditions such as chronic pain, obsessive compulsive disorder, depression and epilepsy. For these illnesses the specific brain region targeted depends upon the illness and the patient's characteristics. As the indications for DBS increase in number, so grows the number of patients that may be helped by this treatment. Increasing numbers of patients are undergoing these procedures for various maladies at our center and at other locations throughout the nation. To achieve optimal clinical results and avoid side effects, the DBS electrode has to be implanted precisely within the targeted region. This was demonstrated elegantly for parkinsonian patients and the dorsolateral STN, but is likely to be the case for most DBS indications. To achieve this optimal electrode localization, many centers perform electrophysiological mapping of the target nuclei using microelectrode recording (MER). This way they can achieve precise localization of the electrode. During the mapping procedure, microelectrodes are passed through the target nuclei, and the electrical neuronal activity is observed and recorded. The surgical team can identify the precise location of the target nuclei and its borders according to the typical activity of its neurons. Dexmedetomidine, propofol and remifentanyl are often used in awake neurosurgical procedures. Dexmedetomidine provides sedation and amnesia with minimal respiratory depression, and improves perioperative hemodynamic stability in neurosurgical patients. Propofol and remifentanil have a much shorter duration of action, and thus allow rapid titration. Both these agents allow reliable and safe sedation for awake craniotomies. However, the effects of any of these three agents on the electrical activity, and whether they will allow safe sedation during DBS electrode implantation at different targets and in different clinical conditions is unclear. This study will compare the activity of neurons in several DBS targets before, during and after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the effects of anesthetics on the neuronal activity in these targets, allowing the study team to choose the most appropriate sedation protocol to use during implantation of DBS electrodes in deep brain structures (bearing in mind that each structure may have a different optimal protocol). The primary aim is to document the effects of commonly used anesthetic drugs on the neuronal activity during MER in different brain structures that are used as targets for DBS implantation. The secondary aims is to Identifying effective sedation regimens for the different DBS targets; (2) Documenting the time course of the different drug's effect on the neuronal activity. Having this information will allow planning and performing sedation during the procedure prior to the MER without affecting the quality of the MER. This may prove useful in cases where no sedation regimen is completely devoid of effect on the MER; (3) Creating a database that includes the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.

Interventions

DRUGRemifentanil

Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the bispectral index (BIS) values to normalize to awake level for the MER.

DRUGPropofol

Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.

DRUGDexmedetomidine

Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.

Sponsors

University of Wisconsin, Madison
Lead SponsorOTHER

Study design

Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No

Inclusion criteria

* All patients scheduled to undergo DBS electrode implantation surgery with MER that agree to participate in the experiment and sign an informed consent are candidates to participate in the study, unless one of the

Exclusion criteria

is met

Design outcomes

Primary

MeasureTime frameDescription
Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity45 minutesEffects of propofol, remifentanil and dexmedetomidine on the neuronal activity during microelectrode recording (MER) in different brain structures that are used as target for DBS implantation will be measure. The RMS of the electrical activity as a measure of the spiking rate of neurons in the vicinity of the electrode tip. normalize the RMS to the baseline value recorded at the first 2-5 minutes of MER (before entering the target area) to compensate for differences between patients and recording electrodes. In order to calculate the change in the normalized RMS following sedation the investigators will compare the mean RMS during 2 minutes of the stable recording of the pre-sedation baseline to the mean RMS during stable sedation and following recovery.

Secondary

MeasureTime frameDescription
Mean Time in Minutes From Sedation to Recoveryup to 57 minutesThis outocme meadsures the mean time from sedation to recovery.
Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs1hrs 30 minThe number of subjects examining the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.

Countries

United States

Participant flow

Participants by arm

ArmCount
Remifentanil
Remifentanil will be administered to subjects during microelectrode recordings (MER). Remifentanil: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.
20
Propofol
Propofol will be administered to subjects during MER. Propofol: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.
0
Dexmedetomidine
Dexmedetomidine will be administered to subjects during MER. Dexmedetomidine: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.
0
Total20

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyWithdrawal by Subject600

Baseline characteristics

CharacteristicRemifentanilTotal
Age, Continuous60 years60 years
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
18 Participants18 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
2 Participants2 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants2 Participants
Race (NIH/OMB)
White
18 Participants18 Participants
Region of Enrollment
United States
20 participants20 participants
Sex: Female, Male
Female
5 Participants5 Participants
Sex: Female, Male
Male
15 Participants15 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 140 / 00 / 0
other
Total, other adverse events
0 / 140 / 00 / 0
serious
Total, serious adverse events
0 / 140 / 00 / 0

Outcome results

Primary

Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity

Effects of propofol, remifentanil and dexmedetomidine on the neuronal activity during microelectrode recording (MER) in different brain structures that are used as target for DBS implantation will be measure. The RMS of the electrical activity as a measure of the spiking rate of neurons in the vicinity of the electrode tip. normalize the RMS to the baseline value recorded at the first 2-5 minutes of MER (before entering the target area) to compensate for differences between patients and recording electrodes. In order to calculate the change in the normalized RMS following sedation the investigators will compare the mean RMS during 2 minutes of the stable recording of the pre-sedation baseline to the mean RMS during stable sedation and following recovery.

Time frame: 45 minutes

Population: No subjects were accrued into the propofol or dexmedetomidine groups as COVID-19 struck and the number of procedures performed decreased substantially during and post-COVID.

ArmMeasureValue (MEAN)Dispersion
RemifentanilSedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity2.69 percent changeStandard Deviation 0.37
Secondary

Mean Time in Minutes From Sedation to Recovery

This outocme meadsures the mean time from sedation to recovery.

Time frame: up to 57 minutes

Population: No subjects were accrued to the propofol or dexmedetomidine groups.

ArmMeasureValue (MEAN)
RemifentanilMean Time in Minutes From Sedation to Recovery29.43 minutes
Secondary

Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs

The number of subjects examining the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.

Time frame: 1hrs 30 min

Population: No subjects were accrued to the propofol or dexmedetomidine groups due to COVID and the decrease in the frequency of the surgery being performed at the hospital.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
RemifentanilNumber of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs14 Participants
PropofolNumber of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs0 Participants
DexmedetomidineNumber of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs0 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026