<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04502550</url>
  </required_header>
  <id_info>
    <org_study_id>STU-2021-0396</org_study_id>
    <nct_id>NCT04502550</nct_id>
  </id_info>
  <brief_title>Brain Networks and Consciousness</brief_title>
  <official_title>Subcortical-cortical Network Dynamics of Anesthesia and Consciousness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      General anesthesia (GA) is a medically induced state of unresponsiveness and unconsciousness,&#xD;
      which millions of people experience every year. Despite its ubiquity, a clear and consistent&#xD;
      picture of the brain circuits mediating consciousness and responsiveness has not emerged.&#xD;
      Studies to date are limited by lack of direct recordings in human brain during medically&#xD;
      induced anesthesia. Our overall hypothesis is that the current model of consciousness,&#xD;
      originally proposed to model disorders and recovery of consciousness after brain injury, can&#xD;
      be generalized to understand mechanisms of consciousness more broadly. This will be studied&#xD;
      through three specific aims. The first is to evaluate the difference in anesthesia&#xD;
      sensitivity in patients with and without underlying basal ganglia pathology. Second is to&#xD;
      correlate changes in brain circuitry with induction and emergence from anesthesia. The third&#xD;
      aim is to evaluate the effects of targeted deep brain stimulation on anesthesia induced loss&#xD;
      and recovery of consciousness. This study focuses on experimentally studying these related&#xD;
      brain circuits by taking advantage of pathological differences in movement disorder patient&#xD;
      populations undergoing deep brain stimulation (DBS) surgery. DBS is a neurosurgical procedure&#xD;
      that is used as treatment for movement disorders, such as Parkinson's disease and essential&#xD;
      tremor, and provides a mechanism to acquire brain activity recordings in subcortical&#xD;
      structures. This study will provide important insight by using human data to shed light on&#xD;
      the generalizability of the current model of consciousness. The subject's surgery for DBS&#xD;
      will be prolonged by up to 40 minutes in order to record the participant's brain activity and&#xD;
      their responses to verbal and auditory stimuli.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 15, 2020</start_date>
  <completion_date type="Anticipated">August 15, 2025</completion_date>
  <primary_completion_date type="Anticipated">February 15, 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Propofol dose response curve</measure>
    <time_frame>baseline</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral assessment of propofol induced loss / recovery of consciousness and responsiveness</measure>
    <time_frame>baseline</time_frame>
    <description>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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electrocorticogram (ECoG) and pallidal Local Field Potential (LFP) recordings</measure>
    <time_frame>baseline</time_frame>
    <description>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.</description>
  </primary_outcome>
  <number_of_groups>7</number_of_groups>
  <enrollment type="Anticipated">144</enrollment>
  <condition>Loss of Consciousness</condition>
  <condition>Parkinson Disease</condition>
  <condition>Essential Tremor</condition>
  <condition>Anesthesia</condition>
  <arm_group>
    <arm_group_label>Parkinson's Disease patients with DBS, no stimulation</arm_group_label>
    <description>This cohort will serve as as the observed group, displaying basal ganglia pathology.&#xD;
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.&#xD;
Experiments will be completed with DBS off.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Essential Tremor patients with DBS</arm_group_label>
    <description>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.&#xD;
Experiments will be completed with DBS off.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parkinson's Disease patients with DBS, Gpi stimulation</arm_group_label>
    <description>This cohort will serve as as the observed group, displaying basal ganglia pathology.&#xD;
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.&#xD;
Participants will be stimulated at the Gpi via DBS leads during propofol induced loss of consciousness.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parkinson's Disease patients with DBS, Gpe stimulation</arm_group_label>
    <description>This cohort will serve as as the observed group, displaying basal ganglia pathology.&#xD;
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.&#xD;
Participants will be stimulated at the Gpe via DBS leads during propofol induced loss of consciousness.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parkinson's Disease patients undergoing DBS surgery, Gpe stimulation</arm_group_label>
    <description>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.&#xD;
Participants will be stimulated at the Gpe via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parkinson's Disease patients undergoing DBS surgery, Gpi stimulation</arm_group_label>
    <description>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.&#xD;
Participants will be stimulated at the Gpi via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parkinson's Disease patients undergoing DBS surgery, no stimulation</arm_group_label>
    <description>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.&#xD;
Participants will not receive any stimulation via DBS leads, and cortical activity will be recorded via ECoG during propofol induced loss of consciousness.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>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.</description>
    <arm_group_label>Essential Tremor patients with DBS</arm_group_label>
    <arm_group_label>Parkinson's Disease patients undergoing DBS surgery, Gpe stimulation</arm_group_label>
    <arm_group_label>Parkinson's Disease patients undergoing DBS surgery, Gpi stimulation</arm_group_label>
    <arm_group_label>Parkinson's Disease patients undergoing DBS surgery, no stimulation</arm_group_label>
    <arm_group_label>Parkinson's Disease patients with DBS, Gpe stimulation</arm_group_label>
    <arm_group_label>Parkinson's Disease patients with DBS, Gpi stimulation</arm_group_label>
    <arm_group_label>Parkinson's Disease patients with DBS, no stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Study participants are Parkinson's disease and essential tremor patients undergoing&#xD;
        revision/replacement of an implantable pulse generator for DBS, or initial DBS&#xD;
        implantation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willingness and ability to cooperate during conscious operative procedure for up to 40&#xD;
             minutes&#xD;
&#xD;
          -  Clinical diagnosis of Parkinson's disease or essential tremor&#xD;
&#xD;
          -  Preoperative MRI without evidence of cortical or subdural adhesions or vascular&#xD;
             abnormalities&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with recent use (within one week) of anticoagulant or antiplatelet agent use&#xD;
&#xD;
          -  Neurocognitive testing indicating amnestic cognitive deficits&#xD;
&#xD;
          -  History of intolerance of propofol or medical indications to use an anesthetic other&#xD;
             than propofol&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nader Pouratian, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Southwestern Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nader Pouratian, MD, PhD</last_name>
    <phone>(214)645-5465</phone>
    <email>nader.pouratian@utsouthwestern.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Emily Koenig, BA</last_name>
    <phone>(214)645-5465</phone>
    <email>emily.koenig@utsouthwestern.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Nader Pouratian</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nader Pouratian, MD,PhD</last_name>
      <phone>214-645-5465</phone>
      <email>nader.pouratian@utsouthwestern.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>January 12, 2023</last_update_submitted>
  <last_update_submitted_qc>January 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Nader Pouratian</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>general anesthesia</keyword>
  <keyword>deep brain stimulation</keyword>
  <keyword>basal ganglia</keyword>
  <keyword>thalamus</keyword>
  <keyword>sensorimotor cortex</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Essential Tremor</mesh_term>
    <mesh_term>Unconsciousness</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Propofol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04502550
org study id: STU-2021-0396
nct id: NCT04502550
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
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.
observational model: Case-Control
time perspective: Prospective
measure: Propofol dose response curve
time frame: baseline
description: 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.
measure: Behavioral assessment of propofol induced loss / recovery of consciousness and responsiveness
time frame: baseline
description: 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).
measure: Electrocorticogram (ECoG) and pallidal Local Field Potential (LFP) recordings
time frame: baseline
description: 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.
arm group label: Parkinson's Disease patients with DBS, no stimulation
description: 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.
arm group label: Essential Tremor patients with DBS
description: 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.
arm group label: Parkinson's Disease patients with DBS, Gpi stimulation
description: 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.
arm group label: Parkinson's Disease patients with DBS, Gpe stimulation
description: 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.
arm group label: Parkinson's Disease patients undergoing DBS surgery, Gpe stimulation
description: 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.
arm group label: Parkinson's Disease patients undergoing DBS surgery, Gpi stimulation
description: 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.
arm group label: Parkinson's Disease patients undergoing DBS surgery, no stimulation
description: 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.
intervention type: Drug
intervention name: Propofol
description: 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.
arm group label: Essential Tremor patients with DBS
arm group label: Parkinson's Disease patients undergoing DBS surgery, Gpe stimulation
arm group label: Parkinson's Disease patients undergoing DBS surgery, Gpi stimulation
arm group label: Parkinson's Disease patients undergoing DBS surgery, no stimulation
arm group label: Parkinson's Disease patients with DBS, Gpe stimulation
arm group label: Parkinson's Disease patients with DBS, Gpi stimulation
arm group label: Parkinson's Disease patients with DBS, no stimulation
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nader Pouratian, MD, PhD
role: Principal Investigator
affiliation: University of Texas Southwestern Medical Center
last name: Nader Pouratian, MD, PhD
phone: (214)645-5465
email: nader.pouratian@utsouthwestern.edu
last name: Emily Koenig, BA
phone: (214)645-5465
email: emily.koenig@utsouthwestern.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Nader Pouratian
investigator title: Professor of Medicine
mesh term: Parkinson Disease
mesh term: Essential Tremor
mesh term: Unconsciousness
mesh term: Propofol
sharing ipd: No