Sensory-specific Peripheral Stimulation for Tremor Management

NCT ID: NCT04501133

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2025-12-31

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.

Conditions

Parkinson's Disease; Essential Tremor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy Participants

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.

Group Type: EXPERIMENTAL

Peripheral electrical stimulation

Intervention Type: 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.

Single pulse TMS

Intervention Type: 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).

Patients

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.

Group Type: EXPERIMENTAL

Peripheral electrical stimulation

Intervention Type: 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.

Single pulse TMS

Intervention Type: 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).

Interventions

Peripheral electrical stimulation

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

Single pulse TMS

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).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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)
• Stable medication doses for at least 30 days prior to study enrollment
• Able to understand and speak English

Exclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Northwestern University

OTHER

Sponsor Role: collaborator

Shirley Ryan AbilityLab

OTHER

Sponsor Role: lead

Responsible Party

Jose Pons

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jose Pons, Ph.D

Role: PRINCIPAL_INVESTIGATOR

Shirley Ryan AbilityLab

Locations

Shirley Ryan AbilityLab

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jose Pons, Ph.D

Role: CONTACT

jpons@sralab.org

312-238-4549

Grace Hoo, BS

Role: CONTACT

ghoo@sralab.org

312-238-4548

Facility Contacts

Jose Pons, Ph.D

Role: primary

jpons@sralab.org

312-238-4549

Grace Hoo, BS

Role: backup

ghoo@sralab.org

312-238-4548

References

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.

Reference Type: DERIVED

PMID: 36603216 (View on PubMed)

Other Identifiers

STU00211930

Identifier Type: -

Identifier Source: org_study_id