Sensory-specific Peripheral Stimulation for Tremor Management

NCT04501133 | Recruiting

• 1 other identifier: STU00211930
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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).

Conditions

Parkinson's Disease; Essential Tremor

Keywords

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

Outcome Measures

Primary Outcomes (4)

• 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).

  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.

• 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).

  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.

• 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).

  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).

• 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).

  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 Outcomes (2)

• Clinical motor score change

  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).

• MRI/rs-fMRI connectivity

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

Study Arms (2)

Healthy Participants

EXPERIMENTAL

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.

Device: Peripheral electrical stimulation; Device: Single pulse TMS

Patients

EXPERIMENTAL

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.

Device: Peripheral electrical stimulation; Device: Single pulse TMS

Interventions

Peripheral electrical stimulation DEVICE

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.

Healthy Participants; Patients

Single pulse TMS DEVICE

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).

Healthy Participants; Patients

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Shirley Ryan AbilityLab: lead
• Northwestern University: collaborator

Study Sites (1)

Shirley Ryan AbilityLab

Chicago, Illinois, 60611, United States

RECRUITING

Related Publications (1)

• Pascual-Valdunciel A, Kurukuti NM, Montero-Pardo C, Barroso FO, Pons JL. Modulation of spinal circuits following phase-dependent electrical stimulation of afferent pathways. J Neural Eng. 2023 Jan 27;20(1). doi: 10.1088/1741-2552/acb087.

  PMID: 36603216 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Essential Tremor

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Jose Pons, Ph.D

  Shirley Ryan AbilityLab

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jose Pons, Ph.D

CONTACT

312-238-4549; jpons@sralab.org

Grace Hoo, BS

CONTACT

312-238-4548; ghoo@sralab.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: August 6, 2020
• Study Start: September 1, 2020
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)