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Brain Networks and Consciousness

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04502550
Recruitment Status : Recruiting
First Posted : August 6, 2020
Last Update Posted : January 13, 2023
Sponsor:
Collaborator:
University of California, Los Angeles
Information provided by (Responsible Party):
Nader Pouratian, University of Texas Southwestern Medical Center

Study Description
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
General anesthesia (GA) is a medically induced state of unresponsiveness and unconsciousness, which millions of people experience every year. Despite its ubiquity, a clear and consistent picture of the brain circuits mediating consciousness and responsiveness has not emerged. Studies to date are limited by lack of direct recordings in human brain during medically induced anesthesia. Our overall hypothesis is that the current model of consciousness, originally proposed to model disorders and recovery of consciousness after brain injury, can be generalized to understand mechanisms of consciousness more broadly. This will be studied through three specific aims. The first is to evaluate the difference in anesthesia sensitivity in patients with and without underlying basal ganglia pathology. Second is to correlate changes in brain circuitry with induction and emergence from anesthesia. The third aim is to evaluate the effects of targeted deep brain stimulation on anesthesia induced loss and recovery of consciousness. This study focuses on experimentally studying these related brain circuits by taking advantage of pathological differences in movement disorder patient populations undergoing deep brain stimulation (DBS) surgery. DBS is a neurosurgical procedure that is used as treatment for movement disorders, such as Parkinson's disease and essential tremor, and provides a mechanism to acquire brain activity recordings in subcortical structures. This study will provide important insight by using human data to shed light on the generalizability of the current model of consciousness. The subject's surgery for DBS will be prolonged by up to 40 minutes in order to record the participant's brain activity and their responses to verbal and auditory stimuli.

Condition or disease Intervention/treatment
Loss of Consciousness Parkinson Disease Essential Tremor Anesthesia Drug: Propofol

Study Design
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Study Type : Observational
Estimated Enrollment : 144 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Subcortical-cortical Network Dynamics of Anesthesia and Consciousness
Actual Study Start Date : October 15, 2020
Estimated Primary Completion Date : February 15, 2025
Estimated Study Completion Date : August 15, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Propofol

Groups and Cohorts
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Group/Cohort Intervention/treatment
Parkinson's Disease patients with DBS, no stimulation

This cohort will serve as as the observed group, displaying basal ganglia pathology.

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.

Experiments will be completed with DBS off.

 Drug: Propofol
Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.
Essential Tremor patients with DBS

This cohort will serve as a control group (no basal ganglia pathology). A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a TCI system to achieve plasma target propofol concentrations. Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.

Experiments will be completed with DBS off.

 Drug: Propofol
Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.
Parkinson's Disease patients with DBS, Gpi stimulation

This cohort will serve as as the observed group, displaying basal ganglia pathology.

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.

Participants will be stimulated at the Gpi via DBS leads during propofol induced loss of consciousness.

 Drug: Propofol
Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.
Parkinson's Disease patients with DBS, Gpe stimulation

This cohort will serve as as the observed group, displaying basal ganglia pathology.

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.

Participants will be stimulated at the Gpe via DBS leads during propofol induced loss of consciousness.

 Drug: Propofol
Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.
Parkinson's Disease patients undergoing DBS surgery, Gpe stimulation

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.

Participants will be stimulated at the Gpe via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.

 Drug: Propofol
Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.
Parkinson's Disease patients undergoing DBS surgery, Gpi stimulation

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.

Participants will be stimulated at the Gpi via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.

 Drug: Propofol
Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.
Parkinson's Disease patients undergoing DBS surgery, no stimulation

A syringe pump controlled by Stanpump implementing the Eleveld Pharmacokinetics-Pharmacodynamics (PK-PD) model for propofol will be used as a targeted controlled infusion (TCI) system to achieve plasma target propofol concentrations. Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.

Participants will not receive any stimulation via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.

 Drug: Propofol
Target effect-site concentration of propofol will be started at 1.4 μg/mL and will be increased by 0.3 μg/mL with reassessment until endpoints are achieved.


Outcome Measures
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Primary Outcome Measures :
  1. Propofol dose response curve [ Time Frame: baseline ]
    Serum concentration of propofol throughout targeted infusion will be correlated with the patient's response to behavioral assessments in order to predict the time course of plasma and effect site concentration of propofol, establishing differential anesthetic sensitivity profiles.

  2. Behavioral assessment of propofol induced loss / recovery of consciousness and responsiveness [ Time Frame: baseline ]
    For each experiment, three behavioral responses will be evaluated: (1) loss/recovery of spontaneous movement (i.e., loss and recovery of responsiveness) (2) loss/recovery of movement in response to stimuli (separately to clicks [non-salient] and verbal stimuli [salient]), and (3) loss/recovery of movement to command (verbal command with patient name with instruction to open their eyes, as proxy of loss/recovery of consciousness).

  3. Electrocorticogram (ECoG) and pallidal Local Field Potential (LFP) recordings [ Time Frame: baseline ]
    Cortical ECoG and Globus Pallidus internus / Globus Pallidus externus (GPi/GPe) LFP recordings will occur during DBS implantation surgery during both induction and emergence with target-controlled infusion of propofol changes in network parameters. Neurophysiological signals will be correlated the evolution of behavioral measures of loss of consciousness and responsiveness during propofol infusion.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Study participants are Parkinson's disease and essential tremor patients undergoing revision/replacement of an implantable pulse generator for DBS, or initial DBS implantation.
Criteria

Inclusion Criteria:

  • Willingness and ability to cooperate during conscious operative procedure for up to 40 minutes
  • Clinical diagnosis of Parkinson's disease or essential tremor
  • Preoperative MRI without evidence of cortical or subdural adhesions or vascular abnormalities

Exclusion Criteria:

  • Patients with recent use (within one week) of anticoagulant or antiplatelet agent use
  • Neurocognitive testing indicating amnestic cognitive deficits
  • History of intolerance of propofol or medical indications to use an anesthetic other than propofol
Contacts and Locations
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04502550


Contacts
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Contact: Nader Pouratian, MD, PhD (214)645-5465 nader.pouratian@utsouthwestern.edu
Contact: Emily Koenig, BA (214)645-5465 emily.koenig@utsouthwestern.edu

Locations
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United States, Texas
Nader Pouratian Recruiting
Dallas, Texas, United States, 75235
Contact: Nader Pouratian, MD,PhD    214-645-5465    nader.pouratian@utsouthwestern.edu   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
University of California, Los Angeles
Investigators
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Principal Investigator: Nader Pouratian, MD, PhD University of Texas Southwestern Medical Center
More Information
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Responsible Party: Nader Pouratian, Professor of Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT04502550    
Other Study ID Numbers: STU-2021-0396
First Posted: August 6, 2020    Key Record Dates
Last Update Posted: January 13, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Nader Pouratian, University of Texas Southwestern Medical Center:
general anesthesia
deep brain stimulation
basal ganglia
thalamus
sensorimotor cortex
Additional relevant MeSH terms:
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Parkinson Disease
Essential Tremor
Unconsciousness
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
 Neurologic Manifestations
Consciousness Disorders
Neurobehavioral Manifestations
Propofol
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics