Clinical trial NCT06846047: Therapeutic Effects of Electrical Vestibular Stimulation (EVS) on Balance and Gait
Official title: Therapeutic Effects of Electrical Vestibular Stimulation (EVS) on Balance and Gait
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Vestibulopathy
Keywords: age-related balance decline
Lead sponsor: Neursantys Inc
Sponsor class: INDUSTRY
Collaborators: name: Mitacs
name: University of Calgary
First posted: 2025-02-25
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Postural Sway Measure of Balance Performance
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
measure: Sensory Integration Measure of Balance Performance
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
measure: Gait Velocity Measure of Gait Performance
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
measure: Gait Cadence Measure of Gait Performance
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
measure: Step Length Measure of Gait Performance
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
measure: Step Trajectory Measure of Gait Performance
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
Secondary outcomes:
measure: Symbol Digit Matching Task (SDMT) Measure of Cognitive Performance
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
measure: Montreal Cognitive Assessment (MoCA) of Cognitive Performance
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
Other outcomes:
measure: Migraine Disability Assessment (MIDAS) of Headaches
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
measure: Dizziness Handicap Inventory (DHI) of Dizziness
timeFrame: From enrollment through the end of treatment and up to 6 months post treatment
Locations:
city: Cupertino
country: United States
facility: Caring Hands Caregivers
state: California
city: Menlo Park
country: United States
facility: Neursantys
state: California
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Dieppe
country: Canada
facility: Sparx Wellness Institute
state: New Brunswick
Study officials:
affiliation: University of Calgary
name: Ryan M Peters, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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