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TerminatedNCT03283150Updated Jul 5, 2024Results posted

Deep Brain Stimulation (DBS) Sedation

A Phase 4 interventional study of Remifentanil and Propofol in Brain and Sedation, sponsored by University of Wisconsin, Madison. Terminated at 1 site in United States. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-07-05.

Sponsored by University of Wisconsin, Madison · Phase 4, Interventional, and Treatment

Why this study was terminated
Due to a decrease in scheduled study-eligible patients, we terminated the study prematurely
Phase
Phase 4
Study type
Interventional
Enrollment
20
Allocation
Non-randomized
Ages
18 Years to 85 Years
Sex
All
01

Study 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).

Read the 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.

02

Conditions studied

  • Brain
  • Sedation

Keywords

  • Deep Brain Stimulation(DBS)
  • Sedation
  • DBS Implantation
  • Microelectrode recording(MER)
03

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts 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

Exclusion criteria

Exclusion Criteria:

  1. Known or suspected obstructive sleep apnea.
  2. Suspected difficult intubation.
  3. Pregnancy (pregnancy test is standard care for women of childbearing age)
  4. Under 18 years of age or over 85 years of age
  5. Cognitive disability impairing understanding the experiment or signing the informed consent form.
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
20 participants (actual)

Study arms

  • Active comparator
    Remifentanil

    Remifentanil will be administered to subjects during microelectrode recordings (MER).

    Drug: Remifentanil

  • Active comparator
    Propofol

    Propofol will be administered to subjects during MER.

    Drug: Propofol

  • Active comparator
    Dexmedetomidine

    Dexmedetomidine will be administered to subjects during MER.

    Drug: Dexmedetomidine

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.

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. Mean Time in Minutes From Sedation to Recovery

    This outocme meadsures the mean time from sedation to recovery.

    Time frame: up to 57 minutes

  2. 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

06

Results

Posted Mar 27, 2023

Participant flow

Participant flow — Overall Study
MilestoneRemifentanilPropofolDexmedetomidine
Started2000
Completed1400
Not completed600
Withdrew: Withdrawal by subject600

Outcome measures

PrimarySedatives 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
Reported as:
Mean · percent change
Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity
percent changeRemifentanilPropofolDexmedetomidine
Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity2.69 ± 0.37——
SecondaryMean Time in Minutes From Sedation to Recovery

This outocme meadsures the mean time from sedation to recovery.

Time frame:
up to 57 minutes
Reported as:
Mean · minutes
Mean Time in Minutes From Sedation to Recovery
minutesRemifentanilPropofolDexmedetomidine
Mean Time in Minutes From Sedation to Recovery29.43 (11 to 57)——
SecondaryNumber 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
Reported as:
Count of participants · Participants
Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs
ParticipantsRemifentanilPropofolDexmedetomidine
Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs1400

Adverse events

Collected over during 1 study visit, up to 4 hours. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Remifentanil0/14 (0%)0/14 (0%)0/14 (0%)
Propofol———
Dexmedetomidine———

Baseline characteristics

No subjects were accrued to the baseline propofol and dexmedetomidine groups. The study was stopped early due to COVID decreasing participant flow and the frequency of the surgery dropping due to surgeon loss.

Age, Continuous
Age, Continuous(years)RemifentanilPropofolDexmedetomidineTotal
Mean60 (52 to 67)——60 (52 to 67)
Sex: Female, Male
Sex: Female, Male(Participants)RemifentanilPropofolDexmedetomidineTotal
Female5——5
Male15——15
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)RemifentanilPropofolDexmedetomidineTotal
Hispanic or Latino0——0
Not Hispanic or Latino18——18
Unknown or Not Reported2——2
Race (NIH/OMB)
Race (NIH/OMB)(Participants)RemifentanilPropofolDexmedetomidineTotal
American Indian or Alaska Native0——0
Asian0——0
Native Hawaiian or Other Pacific Islander0——0
Black or African American0——0
White18——18
More than one race0——0
Unknown or Not Reported2——2
Region of Enrollment
Region of Enrollment(participants)RemifentanilPropofolDexmedetomidineTotal
United States20——20
07

Study locations

1 site
  • University of Wisconsin Hospital and Clinics
    Madison, Wisconsin 53705, United States
08

References and documents

Publications

  • Raz A, Eimerl D, Zaidel A, Bergman H, Israel Z. Propofol decreases neuronal population spiking activity in the subthalamic nucleus of Parkinsonian patients. Anesth Analg. 2010 Nov;111(5):1285-9. doi: 10.1213/ANE.0b013e3181f565f2. Epub 2010 Sep 14. PubMed 20841416 ↗

Study documents

  • Protocol and statistical analysis plan · Feb 17, 2020
  • Informed consent form · Feb 5, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03283150
Lead sponsor
University of Wisconsin, Madison
Responsible party
Sponsor
First posted
Sep 14, 2017
Start date
Dec 1, 2017
Primary completion
Jan 20, 2022
Completion
Jan 20, 2022
Results posted
Mar 27, 2023
Last update
Jul 5, 2024

Study contacts

Corey A Amlong, MD
principal investigator · University of Wisconsin, Madison

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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