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Effects of Stimulation Patterns of Deep Brain Stimulation

Primary Purpose

Parkinson Disease, Essential Tremor, Multiple Sclerosis

Status
Enrolling by invitation
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Therapeutic Stimulation Patterns
Symptogenic Stimulation Patterns
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Parkinson Disease focused on measuring Deep Brain Stimulation, Movement Disorders, Parkinson Disease, Essential Tremor, Subthalamic Nucleus, Globus Pallidus, Thalamus, Tremor, Bradykinesia, Temporal Pattern, Electrical Stimulation, Neuromodulation, PD, ET, MS, STN, GPi, DBS, Nervous System Diseases, Neurodegenerative Diseases

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of Parkinson's Disease (PD), Essential Tremor (ET) or Multiple Sclerosis (MS)
  • Scheduled to undergo Deep Brain Stimulation (DBS) electrode implant or implanted pulse generator (IPG) replacement surgery
  • Neurologically stable
  • Able to understand the study and consent form

Exclusion Criteria:

  • Inability to execute the motor tasks during the study
  • Inability to tolerate withholding anti-parkinsonian and/or anti-tremor medications
  • Clinically ineffective DBS

Sites / Locations

  • University of Florida
  • Emory University
  • Duke University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Therapeutic Stimulation Patterns

Symptogenic Stimulation Patterns

Arm Description

This group will receive temporal patterns of stimulation that are designed to suppress oscillatory neural activity at theta- or beta-frequencies. These patterns are hypothesized to alleviate motor symptoms.

This group will receive symptogenic patterns of stimulation that are designed to exacerbate oscillatory neural activity at theta- or beta-frequencies. These patterns are hypothesized to exacerbate motor symptoms.

Outcomes

Primary Outcome Measures

Tremor Accelerometry
Tremor responses to deep brain stimulation (DBS) may be recorded by an accelerometer in subjects with essential tremor (ET), multiple sclerosis (MS) and tremor-dominant Parkinson's disease (PD). Tremor will be quantified by calculating the total power within a window of the power spectrum of the time series of the tremor, and this measure will be compared across stimulation patterns.
Bradykinesia Finger Tapping
Bradykinesia responses to deep brain stimulation (DBS) may be recorded by a computer mouse in subjects with Parkinson's disease (PD) who do not have dominant tremor symptoms. Bradykinesia will be quantified as the timing of alternating finger presses, a validated test of bradykinesia, and this measure will be compared across stimulation patterns.
Neural Activity
Neural activity consisting of electrically evoked compound action potentials (ECAPs), DBS local evoked potentials (DLEPs) and/or local field potentials (LFPs) may be recorded in response to deep brain stimulation (DBS). Neural activity characteristics will be compared across stimulation patterns and may be correlated with changes in severity of motor symptoms (tremor or bradykinesia).

Secondary Outcome Measures

Electrode Location
Pre- and post-operative brain imaging obtained as part of standard care may be used to determine the location of subjects' implanted DBS electrode contacts. These data may be used to determine the location of the contacts used to record neural activity relative to the brain region targeted for stimulation.

Full Information

First Posted
September 15, 2015
Last Updated
April 19, 2023
Sponsor
Duke University
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Emory University, University of Florida, Boston Scientific Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT02553525
Brief Title
Effects of Stimulation Patterns of Deep Brain Stimulation
Official Title
Effects of Stimulation Patterns of Deep Brain Stimulation
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
June 2, 2016 (Actual)
Primary Completion Date
September 2026 (Anticipated)
Study Completion Date
September 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Emory University, University of Florida, Boston Scientific Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to measure the effects of non-regular temporal patterns of deep brain stimulation (DBS) on motor symptoms and neural activity in persons with Parkinson's disease (PD), essential tremor (ET) or multiple sclerosis (MS). These data will guide the design of novel stimulation patterns that may lead to more effective and reliable treatment with DBS. These data will also enable evaluation of current hypotheses on the mechanisms of action of DBS. Improving our understanding of the mechanisms of action of DBS may lead to full development of DBS as a treatment for Parkinson's disease and may lead to future applications of DBS.
Detailed Description
This study will be conducted in the operating rooms at Duke University Medical Center, Emory University Hospital, University of Florida Shands Hospital or the UF Health Florida Surgical Center. The study will be performed during surgery on subjects who are undergoing implantation of the deep brain stimulation (DBS) system during an awake procedure, or on subjects who are receiving surgical replacement of the implanted pulse generator (IPG) due to depleted batteries. Subjects will receive temporary sterile extensions to the DBS electrode. These temporary extensions will connect to a stimulation and recording system and allow recording of neural activity. Over the course of ~45 minutes different non-regular temporal patterns of stimulation will be delivered unilaterally and the effects on neural activity and movement disorder symptoms will be measured. The stimulus waveform will be a charge-balanced biphasic pulse, with charge restricted to values below the limit set by the DBS IPG manufacturer, 30 μC/cm². After the study is completed, the temporary extensions will be removed, and the ordinary clinical conduct of the procedure will continue for treatment of the patient's movement disorder. Tremor will be measured using an accelerometer in subjects with essential tremor (ET), multiple sclerosis (MS) and tremor-dominant Parkinson's disease (PD). Bradykinesia will be measured using a finger-tapping task on a computer mouse in subjects with Parkinson's disease who do not have dominant tremor symptoms. Subjects will be familiarized with the motor symptom evaluation tasks before surgery, and baseline measurements of tremor or bradykinesia may be recorded. Further, they may be asked to discontinue use of anti-parkinsonian and/or anti-tremor medications overnight prior to the study, to reduce variability of motor symptoms due to the time course of medications. No general anesthesia will be given to subjects during surgery, and the procedure will be performed under local anesthesia to allow subjects to perform the tasks required in this study. Further, no sedation will be given to subjects receiving a replacement IPG, which can cause minor discomfort or anxiety in some patients. Subjects undergoing surgery for electrode implantation will receive monitored anesthesia care (MAC), in which sedation will be administered as needed, such that subjects are still responsive and pathological motor symptoms (tremor or bradykinesia) are present. Following surgery, the subject's pre-operative MRI and post-operative high-resolution CT scans may be used to determine the location of DBS electrode contacts within the brain. However, participation in the study will not modify imaging procedures needed for standard care, and placement of the electrode during DBS implant surgery will not be altered by the research study. There will be no additional costs to subjects as a result of being in this study. Additional operating room costs will be covered by institutional and/or grant resources.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease, Essential Tremor, Multiple Sclerosis
Keywords
Deep Brain Stimulation, Movement Disorders, Parkinson Disease, Essential Tremor, Subthalamic Nucleus, Globus Pallidus, Thalamus, Tremor, Bradykinesia, Temporal Pattern, Electrical Stimulation, Neuromodulation, PD, ET, MS, STN, GPi, DBS, Nervous System Diseases, Neurodegenerative Diseases

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Therapeutic Stimulation Patterns
Arm Type
Experimental
Arm Description
This group will receive temporal patterns of stimulation that are designed to suppress oscillatory neural activity at theta- or beta-frequencies. These patterns are hypothesized to alleviate motor symptoms.
Arm Title
Symptogenic Stimulation Patterns
Arm Type
Experimental
Arm Description
This group will receive symptogenic patterns of stimulation that are designed to exacerbate oscillatory neural activity at theta- or beta-frequencies. These patterns are hypothesized to exacerbate motor symptoms.
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Stimulation Patterns
Intervention Description
During deep brain stimulation (DBS) electrode implantation or implanted pulse generator (IPG) replacement surgery, different stimulation patterns that are designed to suppress oscillatory neural activity at theta- or beta-frequencies will be delivered in randomized order, and the subject will be blinded to the patterns. Neural activity and/or motor symptoms (tremor and/or bradykinesia) will be measured in response to DBS. Measurements will be made during 2- to 8-minute trials, in which stimulation will be off for the first half of the trial, and on for the remaining half. Neural activity and/or motor symptoms will be measured during both the off and on phases. The total amount of time necessary for data collection will be about 45 minutes.
Intervention Type
Procedure
Intervention Name(s)
Symptogenic Stimulation Patterns
Intervention Description
During deep brain stimulation (DBS) electrode implantation or implanted pulse generator (IPG) replacement surgery, different stimulation patterns that are designed to exacerbate oscillatory neural activity at theta- or beta-frequencies will be delivered in randomized order, and the subject will be blinded to the patterns. Neural activity and/or motor symptoms (tremor and/or bradykinesia) will be measured in response to DBS. Measurements will be made during 2- to 8-minute trials, in which stimulation will be off for the first half of the trial, and on for the remaining half. Neural activity and/or motor symptoms will be measured during both the off and on phases. The total amount of time necessary for data collection will be about 45 minutes.
Primary Outcome Measure Information:
Title
Tremor Accelerometry
Description
Tremor responses to deep brain stimulation (DBS) may be recorded by an accelerometer in subjects with essential tremor (ET), multiple sclerosis (MS) and tremor-dominant Parkinson's disease (PD). Tremor will be quantified by calculating the total power within a window of the power spectrum of the time series of the tremor, and this measure will be compared across stimulation patterns.
Time Frame
Day 1
Title
Bradykinesia Finger Tapping
Description
Bradykinesia responses to deep brain stimulation (DBS) may be recorded by a computer mouse in subjects with Parkinson's disease (PD) who do not have dominant tremor symptoms. Bradykinesia will be quantified as the timing of alternating finger presses, a validated test of bradykinesia, and this measure will be compared across stimulation patterns.
Time Frame
Day 1
Title
Neural Activity
Description
Neural activity consisting of electrically evoked compound action potentials (ECAPs), DBS local evoked potentials (DLEPs) and/or local field potentials (LFPs) may be recorded in response to deep brain stimulation (DBS). Neural activity characteristics will be compared across stimulation patterns and may be correlated with changes in severity of motor symptoms (tremor or bradykinesia).
Time Frame
Day 1
Secondary Outcome Measure Information:
Title
Electrode Location
Description
Pre- and post-operative brain imaging obtained as part of standard care may be used to determine the location of subjects' implanted DBS electrode contacts. These data may be used to determine the location of the contacts used to record neural activity relative to the brain region targeted for stimulation.
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of Parkinson's Disease (PD), Essential Tremor (ET) or Multiple Sclerosis (MS) Scheduled to undergo Deep Brain Stimulation (DBS) electrode implant or implanted pulse generator (IPG) replacement surgery Neurologically stable Able to understand the study and consent form Exclusion Criteria: Inability to execute the motor tasks during the study Inability to tolerate withholding anti-parkinsonian and/or anti-tremor medications Clinically ineffective DBS
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Warren M Grill, PhD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27708
Country
United States

12. IPD Sharing Statement

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Effects of Stimulation Patterns of Deep Brain Stimulation

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