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

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.

Study Overview

• Status: Withdrawn
• Conditions: Parkinson Disease; Parkinson
• Intervention / Treatment: Device: Medtronic RC+S DBS system

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: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Passive and Active Rigidity Quantification	Peak resistive torque integral of resistive torque over the pronation and supination Range of Motion (ROM)	6-months
Ballistic Elbow Flexion to a Target: Peak Velocity	Peak velocity	6-months
Ballistic Elbow Flexion to a Target: Stop Reaction Time	Stop reaction time	6-months
Rapid Alternating Pronation-Supination Movements: RMS	Root Mean Square (RMS)-Displacement RMS	6-months
Rapid Alternating Pronation-Supination Movements: Freezing Episodes Duration	Duration of hesitation or arrest (freezing) episodes	6-months
Rapid Alternating Pronation-Supination Movements: Freezing Episodes Number	Number of hesitation or arrest (freezing) episodes	6-months
Gait: Step length	Step length	6-months
Gait: Step Time	Step time	6-months
Gait: Double Support Time	Double support time	6-months
Gait: Obstacles	Percentage of obstacles successfully avoided	6-months
Gait: Freezing Episodes Duration	Duration of freezing episodes	6-months
Gait: Freezing Episodes Number	Number of freezing episodes	6-months

Collaborators and Investigators

• Sponsor: University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: June 10, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: NEUR-2019-27724

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes