NCT02553525

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), dystonia 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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
180

participants targeted

Target at P75+ for not_applicable parkinson-disease

Timeline
9mo left

Started Jun 2016

Longer than P75 for not_applicable parkinson-disease

Geographic Reach
1 country

3 active sites

Status
enrolling by invitation

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress93%
Jun 2016Mar 2027

First Submitted

Initial submission to the registry

September 15, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 17, 2015

Completed
9 months until next milestone

Study Start

First participant enrolled

June 2, 2016

Completed
10.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2027

Last Updated

April 9, 2026

Status Verified

April 1, 2026

Enrollment Period

10.8 years

First QC Date

September 15, 2015

Last Update Submit

April 6, 2026

Conditions

Keywords

Deep Brain StimulationMovement DisordersParkinson DiseaseEssential TremorSubthalamic NucleusGlobus PallidusThalamusTremorBradykinesiaTemporal PatternElectrical StimulationNeuromodulationPDETMSSTNGPiDBSNervous System DiseasesNeurodegenerative Diseases

Outcome Measures

Primary Outcomes (3)

  • 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.

    Day 1

  • 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.

    Day 1

  • 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).

    Day 1

Secondary Outcomes (1)

  • Electrode Location

    Day 1

Study Arms (2)

Therapeutic Stimulation Patterns

EXPERIMENTAL

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.

Procedure: Therapeutic Stimulation Patterns

Symptogenic Stimulation Patterns

EXPERIMENTAL

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.

Procedure: Symptogenic Stimulation Patterns

Interventions

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.

Therapeutic Stimulation Patterns

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.

Symptogenic Stimulation Patterns

Eligibility Criteria

Age21 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

University of Florida

Gainesville, Florida, 32610, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Duke University

Durham, North Carolina, 27708, United States

Location

MeSH Terms

Conditions

Parkinson DiseaseEssential TremorMultiple SclerosisDystoniaMovement DisordersTremorHypokinesiaNervous System DiseasesNeurodegenerative Diseases

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesSynucleinopathiesDemyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesDyskinesiasNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Warren M Grill, PhD

    Duke University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 15, 2015

First Posted

September 17, 2015

Study Start

June 2, 2016

Primary Completion (Estimated)

March 1, 2027

Study Completion (Estimated)

March 1, 2027

Last Updated

April 9, 2026

Record last verified: 2026-04

Locations