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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04011449
• Other study ID #: NEUR-2019-27724
• Status: Withdrawn
• Phase: N/A
• Start date: September 1, 2019
• Est. completion date: December 31, 2020

Study information

• Verified date: April 2021
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson
• Parkinson Disease

Intervention

Device:
• Medtronic RC+S DBS system
Implantation of the Medtronic RC+S Deep Brain Stimulation (DBS) system

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

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