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Sensory-specific Peripheral Stimulation for Tremor Management

Primary Purpose

Parkinson's Disease, Essential Tremor

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Peripheral electrical stimulation

Single pulse TMS

About this trial

This is an interventional basic science trial for Parkinson's Disease focused on measuring Parkinson's Disease, Essential Tremor, Peripheral electrical stimulation, Transcranial magnetic stimulation, High-density electromyography, Electroencephalography, Magnetic resonance imaging

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for Healthy Participants:

Age from 18 to 80 years
No history of a brain and/or skull lesion
Normal hearing and (corrected) vision
Able to understand and give informed consent
No neurological disorders, no tremor
Absence of pathology that could cause abnormal movements of extremities (e.g., epilepsy, stroke, marked arthritis)
Able to understand and speak English

Inclusion Criteria for Patients:

Age from 18 to 80 years
No prior history of skull lesions or craniotomy
Normal hearing and (corrected) vision
Able to understand and give informed consent
Diagnosis of ET (Tremor Research investigation Group criteria) or diagnosis of PD (UK PD Society Brain bank diagnostic criteria) by movement disorder neurologist
Tremor in at least an upper limb with pure flexion-extension wrist tremor with posture (ET) and rest (PD).
Tremor at least moderate-severe by clinician judgment and tremor scales (Fahn Tolosa Marin Tremor Rating Scale, Movement Disorder Society-Unified Parkinson's Disease Rating Scale)
Absence of pathology that could cause abnormal movements of extremities (e.g., epilepsy, stroke, marked arthritis, moderate to severe dyskinesias in PD)
Stable medication doses for at least 30 days prior to study enrollment
Able to understand and speak English

Exclusion Criteria for Healthy Participants:

Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye
Surgical clips in the head or previous neurosurgery
Any magnetic particles in the body
Cochlear implants
Prosthetic heart valves
Epilepsy or any other type of seizure history
Any neurological diagnoses or medications influencing brain function
History of significant head trauma (i.e., extended loss of consciousness, neurological sequelae)
Known structural brain lesion
Significant other disease (heart disease, malignant tumors, mental disorders)
Significant claustrophobia; Ménière's disease
Pregnancy (ruled out by urine ß-HCG if answers to screening questions suggest that pregnancy is possible), breast feeding
Non prescribed drug use
History of current substance abuse (exception: current nicotine use is allowed)
Recreational marijuana
Tremor, parkinsonism; neurological diseases; medical (cardiological, renal, hepatic, oncological) or psychiatric disease that would interfere with study procedures for asES, HD-EMG, TMS, or EEG
Dementia; severe depression; or prior neurosurgical procedures
Failure to perform the behavioral tasks or neuropsychological evaluation tests
Prisoners

Exclusion Criteria for Patients:

Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye
Surgical clips or shunts in the head
Any magnetic particles in the body
Cochlear implants
Prosthetic heart valves
Epilepsy or any other type of seizure history
Significant claustrophobia; Ménière's disease
Pregnancy, breast feeding
Medications increasing risk for seizures
History of current substance abuse (exception: current nicotine use is allowed)
Failure to perform tasks (e.g., follow instructions to stay still in the scanner) or fill in safety screening forms
Prisoners
Atypical or secondary parkinsonism
Co-existence of other neurological diseases
Mixed or complex tremors
Inability or unwillingness to discontinue medications for tremor on the day of study assessments
Medical (cardiological, renal, hepatic, oncological) or psychiatric disease that would interfere with study procedures for asES, HD-EMG, TMS, or EEG; dementia; severe depression; prior neurosurgical procedures

Sites / Locations

Shirley Ryan AbilityLabRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Healthy Participants

Patients

Arm Description

Healthy participants without motor disorders and medications influencing brain functions will be scanned with MRI and undergo PES and/or single pulse TMS during several visits, each with different stimulation patterns, while HD-EMG is recorded.

Participants with Parkinson's Disease or essential tremor will be scanned with MRI and undergo PES and/or single pulse TMS during several visits, each with different stimulation patterns, while HD-EMG and EEG are recorded.

Outcomes

Primary Outcome Measures

Changes in Amount of Motor Inhibition

HD-EMG will be recorded with a 64-channel device (EMG-Quattrocento; 400-channel EMG amplifier, OT Bioelettronica, Italy). The HD-EMG data will be recorded at the wrist level before, during and after muscle contractions. All data will be analyzed offline. Changes in the amount of inhibition will be assessed. The amount of inhibition is calculated as the mean discharge rate across trials and normalized as a percentage of the baseline (100%). To assess the short-term effects, HD-EMG data will be collected before (baseline), during and 1 minute (Post) after PES. Changes in amount of motor inhibition will be measured by comparing the amount of inhibition before (baseline), during and 1 minute after PES (Post). To assess long-term effects, HD-EMG data will be collected at post 24h, post 48h, and post 1 week after PES. The amount of inhibition at 24h, 48h, and 1 week after PES will be compared with the baseline amount of inhibition (before PES).

Changes in motor evoked potentials (MEPs)

To assess the effects of electrical stimulation in motor inhibition, single-pulse TMS will be administered to the contralateral area of the brain while MEPs are recorded from the contralateral site (EMG-Quattrocento; 400-channel EMG amplifier, OT Bioelettronica, Italy). The mean peak-to peak MEP amplitude will be calculated to assess changes in inhibition. To assess the short-term effects, MEP data will be collected before (baseline), during and 5 minutes (Post) after PES. Changes in MEPs will be measured by comparing the MEPs before (baseline), during and 1 minute after PES (Post). To assess long-term effects, MEP data will be collected at post 24h, post 48h, and post 1 week after PES. The MEPs at 24h, 48h, and 1 week after PES will be compared with the baseline MEPs (before PES).

Changes in cortico-muscular coherence in ET and/or PD participants

EEG will be recorded with a 64-channel whole-head device (NeurOne, Bittium, Kuopio, Finland) and HD-EMG with a 64-channels system (EMG-Quattrocento; 400-channel EMG amplifier, OT Bioelettronica, Italy). The coherence between EEG and HD-EMG signals will be computed to assess supraspinal and spinal inhibition. To assess the short- term effects, EEG and HD-EMG data will be collected before (Pre) and 1 minute (Post) after PES. Changes in cortico-muscular coherence will be measured by comparing the cortico-muscular coherence before (baseline) and 1 minute after PES (Post). To assess long-term effects, EEG and HD-EMG data will be collected at post 24h, post 48h, and post 1 week after PES. The cortico-muscular coherence at 24h, 48h, and 1 week after PES will be compared with the baseline cortico-muscular coherence (before PES).

Changes in kinematics

Tremor amplitude will be measured with inertial measurement units that quantify variations in wrist angles during tremor. Specifically, the tremor amplitude will be calculated as the mean peak-to-peak amplitude between maximal wrist flexion and wrist extension angles. To assess the short-term effects, tremor amplitude will be collected before (Pre) and 1 minute (Post) after PES. Changes in tremor amplitude will be measured by comparing the tremor amplitude before (baseline) and 1 minute after PES (Post). To assess long-term effects, tremor amplitude will be recorded at post 24h, post 48h, and post 1 week after PES. The tremor amplitude at 24h, 48h, and 1 week after PES will be compared with the baseline tremor amplitude (before PES).

Secondary Outcome Measures

Clinical motor score change

The MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Fahn Tolosa Marin (FTM) rating scale are functional scales used by clinicians to assess the functional impairments caused by Parkinson's disease and essential tremor, respectively. The MDS-UPDRS and the FTM scales will be used to assess clinical motor changes induced by the PES. To assess the short-term effects, The MDS-UPDRS or the FTM will be administered before and after PES. Changes in scores will be assessed by comparing the MDS-UPDRS/or FTM scores before (baseline) and after PES (Post). To assess long-term effects, the MDS-UPDRS/or FTM scores will be collected at post 24h, post 48h, and post 1 week after PES. The MDS-UPDRS/or FTM scores at 24h, 48h, and 1 week after PES will be compared with the baseline the MDS-UPDRS/or FTM scores (before PES).

MRI/rs-fMRI connectivity

Structural connectivity will be assessed with diffusion tensor imaging (DTI). Functional connectivity will be assessed with resting-state MRI (rs-MRI).

Full Information

NCT ID

NCT04501133

First Posted

July 21, 2020

Last Updated

October 4, 2023

Sponsor

Shirley Ryan AbilityLab

Collaborators

Northwestern University

1. Study Identification

Unique Protocol Identification Number

NCT04501133

Brief Title

Sensory-specific Peripheral Stimulation for Tremor Management

Official Title

Sensory-specific Peripheral Stimulation for Tremor Management

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

September 1, 2020 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Shirley Ryan AbilityLab

Collaborators

Northwestern University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to understand the neurophysiological mechanisms of peripheral electrical stimulation (PES) in modulating supraspinal tremorogenic input to motoneurons. For this purpose, the investigators will use transcutaneous PES, high-density electromyography (HD-EMG), transcranial magnetic stimulation (TMS), electroencephalography (EEG), magnetic resonance imaging (MRI), and neuromusculoskeletal modelling. This study will be carried out in both healthy participants and patients with essential tremor (ET) and Parkinson's disease (PD).

Detailed Description

In Experiment A, the investigators will recruit healthy participants without motor disorders and medications influencing brain function (n = 25). The investigators will characterize inhibition of wrist flexors/wrist extensors and first dorsal interossei (FDI) and abductor pollicis brevis (APB) muscles with PES, and also use TMS to stimulate the corresponding areas in the brain and see if the movement can be reduced through PES. HD-EMG will be used to collect data and identify associated motor unit spike trains. Motor-evoked potentials (MEPs) will be recorded with EMG when TMS is targeted to the primary motor cortex. Resting state functional magnetic imaging resonance (rs-fMRI) and high-angular resolution diffusion imaging (HARDI) tractography of the brain will be recorded. In Experiment B, the investigators will recruit patients with essential tremor (ET) and/or Parkinson's disease (PD) (n = 25 for each pathology). The investigators will repeat the same characterization of inhibition of wrist flexors/wrist extensors and PDI/APB with PES and also use TMS to stimulate corresponding areas in the brain. Additionally, the investigators will test PES conditions as a tremor reduction strategy at the wrist level. The investigators will also test PES conditions at the elbow and shoulder joints as a tremor reduction strategy. Finally, the investigators will observe and characterize the long-term effects (lasting 24h, 48h, and 7 days post stimulation) of PES via coherence between HD-EMG and EEG at the tremor frequency.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson's Disease, Essential Tremor

Keywords

Parkinson's Disease, Essential Tremor, Peripheral electrical stimulation, Transcranial magnetic stimulation, High-density electromyography, Electroencephalography, Magnetic resonance imaging

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

The purpose of this study is to understand how motor activation can be reduced. For this purpose, it will be examined how some muscles of the arm respond to electric and magnetic stimulation. The effects of the electric and/or magnetic stimulation will be recorded non-invasively with HD-EMG.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Healthy Participants

Arm Type

Experimental

Arm Description

Arm Title

Patients

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Peripheral electrical stimulation

Intervention Description

Electrical stimulation will be delivered to forearm muscles with an electrical stimulator (Digitimer Ltd., Hertfordshire, UK) so that they generate forces opposed to those arising from the tremorgenic input.

Intervention Type

Device

Intervention Name(s)

Single pulse TMS

Intervention Description

Single-pulse TMS (spTMS) will be delivered with a TMS stimulator (MagPro X100 w/ MagOption, MagVenture, Farum, Denmark) and a figure-of-eight TMS coil. An MRI-based TMS navigation system will be used to navigate the TMS coil (Localite, St Augustin, Germany).

Primary Outcome Measure Information:

Title

Changes in Amount of Motor Inhibition

Description

Time Frame

Experiment A: Short-term: before vs. during and at 1 minute after PES. Experiment B: Short-term: before vs. during and at 1 minute after PES. Long-term: persistence of changes at post 24 hours, post 48 hours, and post 1 week after PES.

Title

Changes in motor evoked potentials (MEPs)

Description

Time Frame

Experiment A: Short-term: before vs. during and at 5 minutes after PES. Experiment B: Short-term: before vs. during and at 5 minutes after PES. Long-term: persistence of changes at post 24 hours, post 48 hours, and post 1 week after PES.

Title

Changes in cortico-muscular coherence in ET and/or PD participants

Description

Time Frame

Experiment A: N/A. Experiment B: Short-term effects, within sessions (before vs. 1 minute after PES. Long-term effects, across sessions (persistence of changes at post 24 hours, post 48 hours, and post 1 week after PES).

Title

Changes in kinematics

Description

Time Frame

Experiment A: N/A. Experiment B: Short-term effects, within sessions (before vs. 1 minute after PES). Long-term effects, across sessions (persistence of changes at post 24 hours, post 48 hours, and post 1 week after PES).

Secondary Outcome Measure Information:

Title

Clinical motor score change

Description

Time Frame

For Experiment A: N/A. For Experiment B: Short-term effects, within sessions (before and after PES). Long-term effects, across sessions (persistence of changes at 24 hours, 48 hours, and 1-week after PES).

Title

MRI/rs-fMRI connectivity

Description

Structural connectivity will be assessed with diffusion tensor imaging (DTI). Functional connectivity will be assessed with resting-state MRI (rs-MRI).

Time Frame

Experiment A: Baseline and through study completion, an average of 3 months. Experiment B: Baseline and through study completion, an average of 6 months.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria for Healthy Participants: Age from 18 to 80 years No history of a brain and/or skull lesion Normal hearing and (corrected) vision Able to understand and give informed consent No neurological disorders, no tremor Absence of pathology that could cause abnormal movements of extremities (e.g., epilepsy, stroke, marked arthritis) Able to understand and speak English Inclusion Criteria for Patients: Age from 18 to 80 years No prior history of skull lesions or craniotomy Normal hearing and (corrected) vision Able to understand and give informed consent Diagnosis of ET (Tremor Research investigation Group criteria) or diagnosis of PD (UK PD Society Brain bank diagnostic criteria) by a physician Tremor in at least an upper limb with pure flexion-extension wrist tremor with posture (ET) and rest (PD). Tremor at least moderate-severe by clinician judgment and tremor scales (Fahn Tolosa Marin Tremor Rating Scale (TETRAS), Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)) Absence of pathology that could cause abnormal movements of extremities (e.g., epilepsy, stroke, marked arthritis, moderate to severe dyskinesias in PD) Stable medication doses for at least 30 days prior to study enrollment Able to understand and speak English Exclusion Criteria for Healthy Participants: Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye Surgical clips in the head or previous neurosurgery Any magnetic particles in the body Cochlear implants Prosthetic heart valves Epilepsy or any other type of seizure history Any neurological diagnoses or medications influencing brain function History of significant head trauma (i.e., extended loss of consciousness, neurological sequelae) Known structural brain lesion Significant other disease (heart disease, malignant tumors, mental disorders) Significant claustrophobia; Ménière's disease Pregnancy (ruled out by urine ß-HCG if answers to screening questions suggest that pregnancy is possible), breast feeding Non prescribed drug use History of current substance abuse (exception: current nicotine use is allowed) Recreational marijuana Tremor, parkinsonism; neurological diseases; medical (cardiological, renal, hepatic, oncological) or psychiatric disease that would interfere with study procedures for asES, HD-EMG, TMS, or EEG Dementia; severe depression; or prior neurosurgical procedures Failure to perform the behavioral tasks or neuropsychological evaluation tests Prisoners Exclusion Criteria for Patients: Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye Surgical clips or shunts in the head Any magnetic particles in the body Cochlear implants Prosthetic heart valves Epilepsy or any other type of seizure history Significant claustrophobia; Ménière's disease Pregnancy, breast feeding Medications increasing risk for seizures History of current substance abuse (exception: current nicotine use is allowed) Failure to perform tasks (e.g., follow instructions to stay still in the scanner) or fill in safety screening forms Prisoners Atypical or secondary parkinsonism Co-existence of other neurological diseases Mixed or complex tremors Inability or unwillingness to discontinue medications for tremor on the day of study assessments Medical (cardiological, renal, hepatic, oncological) or psychiatric disease that would interfere with study procedures for asES, HD-EMG, TMS, or EEG; dementia; severe depression; prior neurosurgical procedures

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jose Pons, Ph.D

Phone

312-238-4549

jpons@sralab.org

First Name & Middle Initial & Last Name or Official Title & Degree

Grace Hoo, BS

Phone

312-238-4548

ghoo@sralab.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jose Pons, Ph.D

Organizational Affiliation

Shirley Ryan AbilityLab

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shirley Ryan AbilityLab

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jose Pons, Ph.D

Phone

312-238-4549

jpons@sralab.org

First Name & Middle Initial & Last Name & Degree

Grace Hoo, BS

Phone

312-238-4548

ghoo@sralab.org

First Name & Middle Initial & Last Name & Degree

Jose Pons, Ph.D

12. IPD Sharing Statement

Plan to Share IPD

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Sensory-specific Peripheral Stimulation for Tremor Management

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