Therapeutic Effects of Electrical Vestibular Stimulation (EVS) on Balance and Gait (VST)

The aim of the study to is determine the safety, feasibility, efficacy, and persistence of non-invasive EVS to improve balance and gait performance in healthy individuals across the lifespan. Specifically, our objective is to measure balance and gait performance before, during and after exposure to single sessions and across repeated sequences of EVS at multiple study partner sites.

Study Overview

• Status: Recruiting
• Conditions: Vestibulopathy
• Intervention / Treatment: Device: electrical vestibular stimulation (EVS); Device: Sham Comparator

Detailed Description

Background and Rationale

Standing balance and stable gait are maintained through the integration of sensory feedback from the visual, somatosensory (muscle, skin, tendon, and joint receptors), and vestibular systems. The quality of this feedback, and the ability of the central nervous system (brain and spinal cord) to integrate these signals and generate appropriate motor responses dictates balance and gait performance. Age-related balance decline, clinically known as presbystasis, is one of the most visible and debilitating signs of aging. More than 60 million people in the U.S. over the age of 40 live with age-related balance impairments that increase their risks of fall-related injuries and make it increasingly difficult to continue living actively and independently. 1-in-3 adults above the age of 65 falls each year and falls are the leading cause of death in seniors. But there are less than 20,000 clinical specialists in the U.S. with the tools to diagnose balance impairments, so for most people, little is done to address declining balance until after a fall-related injury occurs. The solution offered to most older adults is a mechanical balance aid such as a walker, whose prolonged use only further destabilizes balance.

Vestibular dysfunction has been identified as the primary cause of balance decline in more than 55% of adults over age 50, or around 34 million people in the U.S. This dysfunction impacts both the peripheral vestibular organs in the inner ear and central vestibular processing in the brain, and it has also been linked to cognitive decline. Current therapeutic options to restore lost balance function are limited to high-risk surgical vestibular implants. The current standard of care is exercise-based therapy that aims to help compensate for vestibular balance decline, but there remains a critical gap: no widely available non-invasive solution exists to restore lost vestibular function or prevent further deterioration.

A growing body of research indicates that low-level, non-invasive electrical stimulation of the vestibular balance system (EVS) can induce neuroplastic changes at both cellular and circuit levels, effectively restoring peripheral and central vestibular functions. Restored vestibular function has also been linked to restored cognitive function. The investigators have developed a novel sub-threshold wideband stochastic EVS (swsEVS) neuroplastic stimulation, which targets peripheral and central vestibular pathways. Multiple studies have demonstrated that the swsEVS frequencies and current levels are safe, comfortable, well-tolerated, and have no adverse side effects. These studies have also demonstrated that a therapeutic treatment protocol with 18 twenty-minute swsEVS sessions delivered over a 5-6-week period resulted in significant improvements in balance performance in otherwise healthy adults aged 50-98 years old. These improvements are attributed to neuroplastic restoration of both peripheral and central vestibular function. The observed improvements persisted for at least 3-6 months and were sufficient to recategorize high fall risk individuals to lower fall risk.

Objectives

With the proposed pre-clinical study, the investigators aim to determine the safety, feasibility, efficacy, and persistence of the above non-invasive swsEVS to improve balance and gait performance in healthy individuals across the lifespan. Specifically, our objective is to measure balance and gait performance before, during and after exposure to single sessions and across repeated sequences of swsEVS at multiple study partner sites. The investigators predict that swsEVS-induced neuroplasticity may promote recovery of vestibular function via documented mechanisms that include: 1) regeneration of vestibular hair cells; 2) an increase in synaptic gain in the vestibular system, 3) an increase in vestibular afferent/efferent nerve fibre conductivity and excitability, and 4) increased central neural integration of sensory signals (vestibular, visual, somatosensory) for motor control. As such, our main hypothesis with this research is that exposure to repeated sequences of swsEVS will enhance balance and gait performance (e.g., walking cadence, stability, etc.).

A secondary objective of this study is to determine if changes in vestibular function are accompanied by measurable changes in cognitive function.

Finally, a tertiary objective of this research is to determine if swsEVS has any potential benefit for participants suffering from occasional headaches. There is some anecdotal evidence that EVS could help with headaches, particularly for so-called "vestibular migraines"; however, to date this has not been formally studied.

Participants

Healthy young and older adult participants (18 - 100 years of age) will be recruited in this study. Participants will be recruited at each study site from their local community by word of mouth, study ad postings, and the UCalgary Participate website. All participants will be given detailed written and oral explanations of experimental goals and procedures, and the protocol will be approved by UCalgary's Clinical Health Research Ethics Board (CHREB). Participants will provide written informed consent prior to participation.

Methodology

Participation in this experiment will involve 18 testing sessions over a 5-6- week period, as well as 3-week, 6-week, 3-month, and 6-month follow up sessions. Each testing and follow-up session will last under 1-hour. The proposed project will employ six primary techniques: (i) electrical vestibular stimulation (swsEVS); (ii) accelerometry; (iii) smartphone app-based gait and balance tests; (iv) clinician-administered Functional Gait Assessments; (v) static and dynamic balance tests using an instrumented balance platform; (vi) cognitive assessments. swsEVS test administrators will also collect information about any adverse events during each visit and since the last visit. Participants will also complete questionnaires upon entering and exiting the study to assess the prevalence and severity of headaches, cognition, dizziness, level of physical activity, as well as to determine if these headaches are causing any notable disability.

(i) Electrical Vestibular Stimulation (EVS) involves electrically activating the peripheral vestibular system by passing small electrical currents through electrodes placed on the mastoid processes (behind the ears) via battery powered, constant current isolated stimulators. This non-invasive, safe and painless bioelectronic stimulation technique commonly utilizes either a stochastic signal (white noise) or monopolar or bipolar square- or sine-wave pulses. EVS typically used different bandwidths of stimulation, from broad-band (0-1 kHz) to narrow-band (0-2 Hz).EVS may also be applied at different stimulation amplitudes, ranging from those that are below the level of evoking any sensation by the participant ("sub-threshold"; typically < 0.5 mA), to those that evoke overt vestibular sensations and balance responses ("supra-threshold"; > 0.5 mA). The swsEVS neuroplastic restoration in the present study delivers subthreshold, wideband, stochastic stimuli via 2 pairs of disposable single-use electrodes attached to each mastoid and the back of the neck. EVS does not ever exceed +/- 3 mA (hardware and software limited), giving it an excellent safety profile across a large and growing body of scientific literature.

(ii) Accelerometry: Participants will be instrumented with wearable accelerometers (Phybrata Sensor; PROTXX Inc.) on their head over top of the right mastoid process, as well as on the top of each foot. The sensor placed on the head has been validated as a measure of gait and balance performance in multiple previous studies. The sensors placed on the top of the foot will be used to reconstruct step-by-step foot placement kinematics during gait testing. Sensors attached to the head will be affixed to the skin with disposable double-sided medical adhesive tape, after cleaning the skin with an alcohol swab. Sensors applied to the foot during gait testing will be affixed with medical tape. The accelerometers automatically collect and relay the kinematic data to a smartphone app-based system.

(iii) Smartphone App-Based Gait and Balance Testing: Gait and balance assessments will be performed using a smartphone app developed by PROTXX Inc. The app guides the user through the experimental procedures through on-screen instructions and auditory beeps. Investigators will use the app to perform assessments of quiet standing (3 x 2 min intervals of standing still and relaxed with their arms at their sides; 1 min eyes open, 1 min eyes closed), as well as the standard Timed Up and Go (TUG) task and an over-ground walking task. For the TUG task, participants will start seated in a chair, then when prompted by the app, will stand up, walk 3 m forward to a pilon on the floor, turn around 180 degrees, then return to the chair and sit down. For the over-ground walking task, participants will simply start standing with their toes over a tape line on the floor, then they will walk forward (< 50') to an end target pilon.

(iv) Functional Gait Assessment (FGA): The investigators will have trained clinicians administer the FGA, which involves timing 10 different tests of mobility, including: 1) level surface walking (20'), 2) 'change-in-gait-speed' task alternating between 'slow' and 'fast' speeds (5' each), 3) walking with horizontal head turns every 3 steps (20'), 4) walking with vertical head turns every 3 steps (20'), 5) walking with pivot turn to reverse direction and stop (5'), 6) walking with a step over a 9" obstacle (i.e., the height of 2 shoe boxes), 7) walking with narrow base of support (i.e., stepping 'heel-to-toe') for 10 steps, 8) walking with eyes closed (20'), 9) walking backwards (20'), and 10) walking up and down a set of 4 steps, using a railing if necessary.

(v) Cognitive Assessments: Cognitive assessments will utilize paper-based questionnaire forms of the Symbol Digit Matching Task (SDMT) and the Montreal Cognitive Assessment (MoCA).

Experiment Overview

During their initial intake session at the study site, all participants will undergo EVS threshold testing to determine normalized levels of EVS that result in balance perturbations. This EVS threshold testing will be carried out by administering very low currents (starting at ~0.1 mA) to participants standing with their eyes closed and increasing the current level across trials until an EVS balance threshold is determined.

During all 18 subsequent testing sessions, participants will perform gait and balance tests administered via a smartphone app (see below) before and after a single continuous session of swsEVS (<20 min). During each swsEVS session, participants will alternate between sitting, standing on the hard floor, and standing on a foam pad, with intervals of having their eyes open and closed. An investigator will always be nearby the participants to protect them from falling and provide postural support if needed.

Cognitive testing and headache questionnaires will be completed during the first and last of the 18 treatment sessions.

During the 3-week, 6-week, 3-month, and 6-month follow up sessions, participants will repeat gait and balance tests to assess the persistence of any performance improvements measured after the 18 testing sessions.

Statistical Design

To determine the therapeutic efficacy of repeated EVS sessions, dependent variables will be submitted to repeated measures ANCOVA with stimulation type ('sub-threshold', 'supra-threshold') and sex ('male', 'female') as between subject factors, and age as a covariate. Further exploratory analysis of relationships between age and different dependent variables will be performed using Pearson correlations. An alpha level of 0.05 will be used as the statistical significance threshold for all testing.

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ryan M Peters, PhD; Phone Number: 403-606-5506; Email: ryan.peters1@ucalgary.ca
• Study Contact Backup: Name: John D Ralston, PhD; Phone Number: 650-2158-418; Email: john.ralston@neursantys.com

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 1N4
      • Recruiting
      • University of Calgary
      • Contact: Ryan M Peters, PhD; Phone Number: 403-606-5506; Email: ryan.peters1@ucalgary.ca
  • New Brunswick
    • Dieppe, New Brunswick, Canada, E1A 1P2
      • Recruiting
      • Sparx Wellness Institute
      • Contact: Leon DesRoches; Phone Number: 506-857-8888; Email: leon@sparxwellness.ca
• United States
  • California
    • Cupertino, California, United States, 95014
      • Recruiting
      • Caring Hands Caregivers
      • Contact: Scott Stanley; Phone Number: 408-775-7626; Email: scott@chcgivers.com
    • Menlo Park, California, United States, 94025
      • Recruiting
      • Neursantys
      • Contact: John D Ralston, PhD; Phone Number: 650-215-8418; Email: john.ralston@neursantys.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Able to complete balance assessments such as standing with feet together/eyes open and feet together/eyes closed, both for at least 1 minute at a time, with no more than 1 minute rest required between tests.
2. Able to complete gait assessment tests such as walking up to 200m on a flat surface without assistance.

Exclusion Criteria:

1. Participants must not be using a pacemaker, cochlear implant, or any other implanted electronic device.
2. Participants must be free from any diagnosed neurological or musculoskeletal injuries and/or disorders other than those explicitly being investigated (i.e., vertigo, multiple sclerosis, Parkinson's disease, concussion).
3. Participants must have the mental capacity to provide consent and perform tasks required by the experiment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Electrical vestibular stimulation treatment; Participants in this Arm will receive active treatment with swsEVS applied	Device: electrical vestibular stimulation (EVS); EVS involves electrically activating the vestibular nerves by passing small electrical currents through electrodes placed on the mastoid processes (behind the ears) via battery powered, constant current isolated stimulators.
Sham Comparator: Sham stimulation treatment; Participants in this Arm will receive sham treatment with no swsEVS applied.	Device: Sham Comparator; No current is applied during EVS treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postural Sway Measure of Balance Performance	Postural sway will be calculated from acceleration profiles of the head measured using data from a head-mounted accelerometer in eyes open and eyes closed conditions. The raw acceleration signals are in units of G. The outcome measure is expressed as a sway power value (in Watts). Sway power measured during static standing has been shown to be a precise, quickly administered assessment of balance performance with excellent sensitivity in the identification of older adult fallers. We will complete the above 2-minute postural sway assessment (60 seconds eyes open followed by 60 seconds eyes closed) immediately before and after each of the 18 EVS treatment sessions in order to track each study participant's changes in balance performance following each treatment session and the cumulative change following completion of the 18 session treatment protocol.	From enrollment through the end of treatment and up to 6 months post treatment
Sensory Integration Measure of Balance Performance	Sensory integration will be calculated from acceleration profiles of the head measured using data from a head-mounted accelerometer in eyes open and eyes closed conditions. The raw acceleration signals are in units of G. The outcome measure is calculated using a frequency spectrum analysis of the normalized contributions of the three sensory inputs (visual, vestibular, proprioceptive) to balance control. Sensory integration measured during static standing using wearable sensors or computerized dynamic posturography has been shown to be a precise, quickly administered assessment of sensory contributions to balance control with excellent sensitivity in the identification of sensory impairments that disrupt balance in older adults. Sensory reweighting will be calculated using the head acceleration data from the above 2-minute postural sway assessment (60 seconds eyes open followed by 60 seconds eyes closed) immediately before and after each of the 18 EVS treatment sessions in order to tr	From enrollment through the end of treatment and up to 6 months post treatment
Gait Velocity Measure of Gait Performance	Dynamic gait performance will be measured using data from a head-mounted accelerometer. The raw acceleration signals are in units of G. For dynamic gait tasks, the outcome measures will be the peak walking speed (in Meters per Second) achieved over a set of pre-defined distances from 3 meters to 100 meters. Wearable sensor-based gait velocity tests are widely used in research for older adults with and without pathology, and have norm referenced values and robust clinimetric properties. The above gait velocity measurements will be carried out prior to the first EVS treatment session and following the final (18th) EVS treatment session in order to track the cumulative change in each study participant's gait performance following completion of the 18 session treatment protocol.	From enrollment through the end of treatment and up to 6 months post treatment
Gait Cadence Measure of Gait Performance	Dynamic gait performance will be measured using data from a head-mounted accelerometer. The raw acceleration signals are in units of G. For dynamic gait tasks, the outcome measures will be gait cadence (in Steps per Second) over a set of pre-defined distances from 3 meters to 100 meters. Wearable sensor-based gait cadence tests are widely used in research for older adults with and without pathology, and have norm referenced values and robust clinimetric properties. The above gait cadence measurements will be carried out prior to the first EVS treatment session and following the final (18th) EVS treatment session in order to track the cumulative change in each study participant's gait performance following completion of the 18 session treatment protocol.	From enrollment through the end of treatment and up to 6 months post treatment
Step Length Measure of Gait Performance	Dynamic gait performance will be measured using data from a head-mounted accelerometer. The raw acceleration signals are in units of G. For dynamic gait tasks, the outcome measures will be step length (in Meters) over a set of pre-defined distance from 3 meters to 100 meters. Wearable sensor-based step length tests are widely used in research for older adults with and without pathology, and have norm referenced values and robust clinimetric properties. The above step length measurements will be carried out prior to the first EVS treatment session and following the final (18th) EVS treatment session in order to track the cumulative change in each study participant's gait performance following completion of the 18 session treatment protocol.	From enrollment through the end of treatment and up to 6 months post treatment
Step Trajectory Measure of Gait Performance	Dynamic gait performance will be measured using data from a head-mounted accelerometer. The raw acceleration signals are in units of G. For dynamic gait tasks, the outcome measures will be the distribution of head trajectories during each step (in Angular Degrees) over a set of pre-defined distances from 3 meters to 100 meters. Wearable sensor-based step trajectory tests are widely used in research for older adults with and without pathology, and have norm referenced values and robust clinimetric properties. The above step trajectory measurements will be carried out prior to the first EVS treatment session and following the final (18th) EVS treatment session in order to track the cumulative change in each study participant's gait performance following completion of the 18 session treatment protocol.	From enrollment through the end of treatment and up to 6 months post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symbol Digit Matching Task (SDMT) Measure of Cognitive Performance	This secondary outcome variable will measure changes in cognitive performance scores before vs. after the 18-session EVS intervention period of the study. For assessment of cognitive performance, the measurement scale will be the Symbol Digit Matching Task (SDMT). SDMT quantifies the number of symbol-digit matching pairs the participant completes in 90 seconds.	From enrollment through the end of treatment and up to 6 months post treatment
Montreal Cognitive Assessment (MoCA) of Cognitive Performance	This secondary outcome variable will measure changes in cognitive performance scores before vs. after the 18-session EVS intervention period of the study. For assessment of cognitive performance, the measurement scale will be the Montreal Cognitive Assessment (MoCA). The MoCA is scored on a 0 to 30 scale.	From enrollment through the end of treatment and up to 6 months post treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Migraine Disability Assessment (MIDAS) of Headaches	For participants suffering from headaches, this tertiary outcome variable will determine if there are any changes after vs. before the 18-session EVS intervention period. For assessments of headaches, the measurement scales will be the Migraine Disability Assessment (MIDAS). The MIDAS is scored by totaling the number of days indicated by the user across a 5-item questionnaire.	From enrollment through the end of treatment and up to 6 months post treatment
Dizziness Handicap Inventory (DHI) of Dizziness	For participants suffering from dizziness, this tertiary outcome variable will determine if there are any changes after vs. before the 18-session EVS intervention period. For assessments of dizziness, the measurement scale will be the Dizziness Handicap Inventory (DHI). The DHI is scored by totaling the value indicated by the subject (0 = No, 2 = Sometimes, 3 = Always) across a 25-item questionnaire.	From enrollment through the end of treatment and up to 6 months post treatment

Collaborators and Investigators

• Sponsor: Neursantys Inc
• Collaborators: Mitacs; University of Calgary
• Investigators: Principal Investigator: Ryan M Peters, PhD, University of Calgary

Publications and helpful links

General Publications

• Iwasaki S, Yamasoba T. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System. Aging Dis. 2014 Feb 9;6(1):38-47. doi: 10.14336/AD.2014.0128. eCollection 2015 Feb.
• Ralston JD, Raina A, Benson BW, Peters RM, Roper JM, Ralston AB. Physiological Vibration Acceleration (Phybrata) Sensor Assessment of Multi-System Physiological Impairments and Sensory Reweighting Following Concussion. Med Devices (Auckl). 2020 Dec 8;13:411-438. doi: 10.2147/MDER.S279521. eCollection 2020.
• 13. King J, Walters N, Clark S, Mehri N, Al Bastami J, Chan A, Ferrier E, Rodrigues N, Rempel J, Ralston JD, Peters RM. "Electrical Vestibular Stimulation for Therapeutic Balance Enhancement in Older Adults". Submitted for publication, 2024.
• 12. Ralston JD, King JA, Rempel J, Peters RM, Chima B. "PHYBRATA Biomarker Assessments of Age-Related Balance Impairments and EVS Balance Restoration." 2023 Biomarkers of Aging Symposium, Buck Institute for Research on Aging, Novato, California, USA, Dec 4, 2023.
• 11. King JA, Banman CJ, Walters N, Clark S, Ralston JD, Peters RM. "Electrical Vestibular Stimulation Therapeutics for Balance and Gait in Older Adults." Canadian Association on Gerontology 52nd Annual Scientific and Educational Meeting, CAG2023, Toronto, Ontario, Canada, October 26-28, 2023.
• 10. Ralston JD, King J, Rempel J, Peters RM. "Wearable Bioelectronic Balance Restoration in Older Adults." AGE-WELL Annual Conf, Toronto, Ontario, Oct 24-26, 2023.
• Dilda V, MacDougall HG, Curthoys IS, Moore ST. Effects of Galvanic vestibular stimulation on cognitive function. Exp Brain Res. 2012 Jan;216(2):275-85. doi: 10.1007/s00221-011-2929-z. Epub 2011 Nov 11.
• Lopez C, Cullen KE. Electrical stimulation of the peripheral and central vestibular system. Curr Opin Neurol. 2024 Feb 1;37(1):40-51. doi: 10.1097/WCO.0000000000001228. Epub 2023 Oct 25.
• Pires APBA, Silva TR, Torres MS, Diniz ML, Tavares MC, Goncalves DU. Galvanic vestibular stimulation and its applications: a systematic review. Braz J Otorhinolaryngol. 2022 Nov-Dec;88 Suppl 3(Suppl 3):S202-S211. doi: 10.1016/j.bjorl.2022.05.010. Epub 2022 Jul 5.
• Dlugaiczyk J, Gensberger KD, Straka H. Galvanic vestibular stimulation: from basic concepts to clinical applications. J Neurophysiol. 2019 Jun 1;121(6):2237-2255. doi: 10.1152/jn.00035.2019. Epub 2019 Apr 17.
• Deveze A, Bernard-Demanze L, Xavier F, Lavieille JP, Elziere M. Vestibular compensation and vestibular rehabilitation. Current concepts and new trends. Neurophysiol Clin. 2014 Jan;44(1):49-57. doi: 10.1016/j.neucli.2013.10.138. Epub 2013 Nov 6.
• Smith PF. Aging of the vestibular system and its relationship to dementia. Curr Opin Neurol. 2024 Feb 1;37(1):83-87. doi: 10.1097/WCO.0000000000001231. Epub 2023 Nov 30.
• 3. Agrawal Y, Smith PF, Merfeld DM, "6.36 - Dizziness, Imbalance and Age-Related Vestibular Loss, Editor(s): Bernd Fritzsch, The Senses: A Comprehensive Reference (Second Edition)." Elsevier,2020, p. 567-580, ISBN 9780128054093.
• Davis LE. Dizziness in elderly men. J Am Geriatr Soc. 1994 Nov;42(11):1184-8. doi: 10.1111/j.1532-5415.1994.tb06986.x.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 20, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: age-related balance decline
• Other Study ID Numbers: REB22-1006_MOD4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: de-identified balance and gait performance data
• IPD Sharing Time Frame: Start date: March 1, 2027 End date: March 1, 2029
• IPD Sharing Access Criteria: Study participants and other research groups studying age-related balance decline.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No