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出境医 / 临床实验 / State-dependent Pathophysiological Oscillations in Parkinson's Disease and Treatment With DBS Using the Medtronic RC+S

State-dependent Pathophysiological Oscillations in Parkinson's Disease and Treatment With DBS Using the Medtronic RC+S

Study Description
Brief Summary:

Primary objectives.

The ability of the RC+S to record Local Field Potentials (LFP's) is novel in Deep Brain Stimulation (DBS) technology. The primary goals of this project are to use this function of the RC+S to characterize:

  1. The state- and target-dependency of neuronal oscillations in the subthalamic nucleus (STN), internal globus pallidus (GPi) or external globus pallidus (GPe) of patients with PD,
  2. How these oscillations are altered by levodopa,
  3. The effects of unilateral standard clinical isochronal (e.g. 140 Hz) GPi-, GPe-, and STN-DBS on oscillatory activity and its relationship to the presence and severity of parkinsonian motor signs.

These experiments will leverage the capacity to record LFPs from macroelectrodes implanted in either the GPi/GPe or STN using the Medtronic RC+S DBS system. The long-term goal for this project is to develop closed-loop methods for DBS that are state (resting vs. movement) and movement-phase appropriate.

Secondary objectives.

In addition to establishing the relationship between neural oscillations in the STN, GPi and GPe to clinical and quantitative measures of akinesia, bradykinesia, tremor and rigidity, this project will also examine the relationship of neural oscillations to:

  1. Levodopa-resistant motor features such as postural instability and gait (including freezing of gait),
  2. Response inhibition and impulse control.

Condition or disease Intervention/treatment Phase
Parkinson Disease Parkinson Device: Medtronic RC+S DBS system Not Applicable

Detailed Description:

The Olympus Research System (RC+S) is an implantable pulse generator (IPG) designed to deliver deep brain stimulation (DBS) like a standard clinical neurostimulator, but which allows recordings of local field potential (LFP) activity from the implanted DBS lead.

LFPs are composite electrical signals generated by the brain. They are conventionally divided into frequency bands, as follows: 0-3 Hz (delta), 4-7 Hz (theta), 8-12 Hz (alpha), 13-30 Hz (beta), 31-200 Hz (gamma), and >200 Hz (high frequency). The instantaneous amplitude and power of the LFP recordings are believed to represent the degree of synchronization among neurons surrounding the electrode. A transient increase in power in a particular band, in response to a behavioral event, is called an event-related synchronization (ERS), while a transient decrease in power is called event-related desynchronization (ERD). ERD and ERS are typically calculated by averaging the power across time segments and comparing this average to a reference epoch.

Research staff at the University of Minnesota will follow FDA guidelines for software development for the RC+S.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: State-dependent Pathophysiological Oscillations in Parkinson's Disease and Treatment With DBS Using the Medtronic RC+S
Actual Study Start Date : September 1, 2019
Actual Primary Completion Date : December 31, 2020
Actual Study Completion Date : December 31, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: Device Implantation
Implantation of the Medtronic RC+S Deep Brain Stimulation (DBS) system
Device: Medtronic RC+S DBS system
Implantation of the Medtronic RC+S Deep Brain Stimulation (DBS) system

Outcome Measures
Primary Outcome Measures :
  1. Passive and Active Rigidity Quantification [ Time Frame: 6-months ]
    Peak resistive torque integral of resistive torque over the pronation and supination Range of Motion (ROM)

  2. Ballistic Elbow Flexion to a Target: Peak Velocity [ Time Frame: 6-months ]
    Peak velocity

  3. Ballistic Elbow Flexion to a Target: Stop Reaction Time [ Time Frame: 6-months ]
    Stop reaction time

  4. Rapid Alternating Pronation-Supination Movements: RMS [ Time Frame: 6-months ]
    Root Mean Square (RMS)-Displacement RMS

  5. Rapid Alternating Pronation-Supination Movements: Freezing Episodes Duration [ Time Frame: 6-months ]
    Duration of hesitation or arrest (freezing) episodes

  6. Rapid Alternating Pronation-Supination Movements: Freezing Episodes Number [ Time Frame: 6-months ]
    Number of hesitation or arrest (freezing) episodes

  7. Gait: Step length [ Time Frame: 6-months ]
    Step length

  8. Gait: Step Time [ Time Frame: 6-months ]
    Step time

  9. Gait: Double Support Time [ Time Frame: 6-months ]
    Double support time

  10. Gait: Obstacles [ Time Frame: 6-months ]
    Percentage of obstacles successfully avoided

  11. Gait: Freezing Episodes Duration [ Time Frame: 6-months ]
    Duration of freezing episodes

  12. Gait: Freezing Episodes Number [ Time Frame: 6-months ]
    Number of freezing episodes


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   45 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of idiopathic PD.
  • Age 45-75 years
  • Demonstrated good response (≥ 30%) to Sinemet or dopamine agonist medications as assessed by total UPDRS III score (off and on meds)
  • Clinical plan for unilateral STN- or GPi-DBS surgery to treat their clinical motor signs within the next four months
  • Written documentation of willingness to participate in the study per protocol as evidenced by the informed consent process

Exclusion Criteria:

  • Clinically significant medical disease that would increase the risk of developing pre- or post-operative complications (e.g., major cardiac or pulmonary disease)
  • Evidence of secondary or atypical parkinsonism
  • Dementia as evidenced by impairment in two neuropsychological domains and impaired or borderline neuropsychological function in one additional domain.
  • Unable to undergo MR imaging (e.g., due to incompatible implanted pacemaker)
  • Previous pallidotomy or DBS surgery
  • Women who are currently pregnant
  • MRI brain abnormalities that could indicate a neurological disorder other than idiopathic Lewy body Parkinson's disease.
  • Subjects with severe or poorly controlled depression defined according to DSM-V criteria and a scored on a validated depression assessment scale.
  • Epilepsy
  • Immunocompromised
  • Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) to treat a chronic condition
  • Has an implanted electronic device such as a neurostimulator, cardiac pacemaker or medication pump.
Contacts and Locations

Locations
Layout table for location information
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota
Tracking Information
First Submitted Date  ICMJE June 10, 2019
First Posted Date  ICMJE July 8, 2019
Last Update Posted Date April 9, 2021
Actual Study Start Date  ICMJE September 1, 2019
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 3, 2019)
  • Passive and Active Rigidity Quantification [ Time Frame: 6-months ]
    Peak resistive torque integral of resistive torque over the pronation and supination Range of Motion (ROM)
  • Ballistic Elbow Flexion to a Target: Peak Velocity [ Time Frame: 6-months ]
    Peak velocity
  • Ballistic Elbow Flexion to a Target: Stop Reaction Time [ Time Frame: 6-months ]
    Stop reaction time
  • Rapid Alternating Pronation-Supination Movements: RMS [ Time Frame: 6-months ]
    Root Mean Square (RMS)-Displacement RMS
  • Rapid Alternating Pronation-Supination Movements: Freezing Episodes Duration [ Time Frame: 6-months ]
    Duration of hesitation or arrest (freezing) episodes
  • Rapid Alternating Pronation-Supination Movements: Freezing Episodes Number [ Time Frame: 6-months ]
    Number of hesitation or arrest (freezing) episodes
  • Gait: Step length [ Time Frame: 6-months ]
    Step length
  • Gait: Step Time [ Time Frame: 6-months ]
    Step time
  • Gait: Double Support Time [ Time Frame: 6-months ]
    Double support time
  • Gait: Obstacles [ Time Frame: 6-months ]
    Percentage of obstacles successfully avoided
  • Gait: Freezing Episodes Duration [ Time Frame: 6-months ]
    Duration of freezing episodes
  • Gait: Freezing Episodes Number [ Time Frame: 6-months ]
    Number of freezing episodes
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE State-dependent Pathophysiological Oscillations in Parkinson's Disease and Treatment With DBS Using the Medtronic RC+S
Official Title  ICMJE State-dependent Pathophysiological Oscillations in Parkinson's Disease and Treatment With DBS Using the Medtronic RC+S
Brief Summary

Primary objectives.

The ability of the RC+S to record Local Field Potentials (LFP's) is novel in Deep Brain Stimulation (DBS) technology. The primary goals of this project are to use this function of the RC+S to characterize:

  1. The state- and target-dependency of neuronal oscillations in the subthalamic nucleus (STN), internal globus pallidus (GPi) or external globus pallidus (GPe) of patients with PD,
  2. How these oscillations are altered by levodopa,
  3. The effects of unilateral standard clinical isochronal (e.g. 140 Hz) GPi-, GPe-, and STN-DBS on oscillatory activity and its relationship to the presence and severity of parkinsonian motor signs.

These experiments will leverage the capacity to record LFPs from macroelectrodes implanted in either the GPi/GPe or STN using the Medtronic RC+S DBS system. The long-term goal for this project is to develop closed-loop methods for DBS that are state (resting vs. movement) and movement-phase appropriate.

Secondary objectives.

In addition to establishing the relationship between neural oscillations in the STN, GPi and GPe to clinical and quantitative measures of akinesia, bradykinesia, tremor and rigidity, this project will also examine the relationship of neural oscillations to:

  1. Levodopa-resistant motor features such as postural instability and gait (including freezing of gait),
  2. Response inhibition and impulse control.
Detailed Description

The Olympus Research System (RC+S) is an implantable pulse generator (IPG) designed to deliver deep brain stimulation (DBS) like a standard clinical neurostimulator, but which allows recordings of local field potential (LFP) activity from the implanted DBS lead.

LFPs are composite electrical signals generated by the brain. They are conventionally divided into frequency bands, as follows: 0-3 Hz (delta), 4-7 Hz (theta), 8-12 Hz (alpha), 13-30 Hz (beta), 31-200 Hz (gamma), and >200 Hz (high frequency). The instantaneous amplitude and power of the LFP recordings are believed to represent the degree of synchronization among neurons surrounding the electrode. A transient increase in power in a particular band, in response to a behavioral event, is called an event-related synchronization (ERS), while a transient decrease in power is called event-related desynchronization (ERD). ERD and ERS are typically calculated by averaging the power across time segments and comparing this average to a reference epoch.

Research staff at the University of Minnesota will follow FDA guidelines for software development for the RC+S.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Parkinson Disease
  • Parkinson
Intervention  ICMJE Device: Medtronic RC+S DBS system
Implantation of the Medtronic RC+S Deep Brain Stimulation (DBS) system
Study Arms  ICMJE Experimental: Device Implantation
Implantation of the Medtronic RC+S Deep Brain Stimulation (DBS) system
Intervention: Device: Medtronic RC+S DBS system
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: April 6, 2021)
0
Original Estimated Enrollment  ICMJE
 (submitted: July 3, 2019)
10
Actual Study Completion Date  ICMJE December 31, 2020
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of idiopathic PD.
  • Age 45-75 years
  • Demonstrated good response (≥ 30%) to Sinemet or dopamine agonist medications as assessed by total UPDRS III score (off and on meds)
  • Clinical plan for unilateral STN- or GPi-DBS surgery to treat their clinical motor signs within the next four months
  • Written documentation of willingness to participate in the study per protocol as evidenced by the informed consent process

Exclusion Criteria:

  • Clinically significant medical disease that would increase the risk of developing pre- or post-operative complications (e.g., major cardiac or pulmonary disease)
  • Evidence of secondary or atypical parkinsonism
  • Dementia as evidenced by impairment in two neuropsychological domains and impaired or borderline neuropsychological function in one additional domain.
  • Unable to undergo MR imaging (e.g., due to incompatible implanted pacemaker)
  • Previous pallidotomy or DBS surgery
  • Women who are currently pregnant
  • MRI brain abnormalities that could indicate a neurological disorder other than idiopathic Lewy body Parkinson's disease.
  • Subjects with severe or poorly controlled depression defined according to DSM-V criteria and a scored on a validated depression assessment scale.
  • Epilepsy
  • Immunocompromised
  • Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) to treat a chronic condition
  • Has an implanted electronic device such as a neurostimulator, cardiac pacemaker or medication pump.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04011449
Other Study ID Numbers  ICMJE NEUR-2019-27724
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Minnesota
Study Sponsor  ICMJE University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Minnesota
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP