The Neural Mechanisms of Split-belt Treadmill Adaptation in People With Multiple Sclerosis

NCT05878873 | Completed Results FDA Device

• 1 other identifier: 1664
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Majority of people with multiple sclerosis experience difficulty with balance and mobility, leading to an increased risk of falls. The goal of this clinical trial is to learn about brain activity during walking adaptation in people with multiple sclerosis. Also, this clinical trial will test a form of nerve stimulation to see if it can improve walking performance. The main questions it aims to answer are:

• What areas of the brain are the most active during walking adaptation?
• Can nerve stimulation make walking adaptation more effective? Participants will walk on a treadmill where each leg will go a different speed which will create walking adaptation. At the same time, brain scans will occur. There will be two sessions of walking adaptation, one with nerve stimulation, and one without nerve stimulation. Researchers will compare people with multiple sclerosis to healthy young adults to see if there are differences in brain activity.

Conditions

Multiple Sclerosis

Keywords

split-belt treadmill; adaptation; multiple sclerosis; functional near-infrared spectroscopy; cortical activation; gait asymmetry; locomotion; sensorimotor control

Outcome Measures

Primary Outcomes (3)

• Change in Cortical Activation

  Cortical activation is measured using functional near-infrared spectroscopy (fNIRS) during split-belt treadmill walking. Hemodynamic responses are modeled using a general linear model (GLM) applied to the oxyhemoglobin (HbO) signal. The model includes regressors for distinct phases of walking, with the primary contrast comparing early adaptation (strides 6-30 after split-belt onset) to a baseline walking period. The outcome is defined as the difference in this HbO beta weight contrast with TENS ON compared to TENS OFF. Activation is averaged across all fNIRS channels to provide a whole-brain estimate of cortical activity. A larger value indicates a greater increase in activation from baseline walking to early adaptation. This was measured on both training session 1 and training session 2 to account for the crossover design (i.e. participants are receiving TENS on different days).

  Training session 1 (day 1), training session 2 (day 28)

• Change in Adaptation Savings

  Adaptation savings is defined as the difference in early adaptation performance between training session 1 (Day 1) and training session 2 (Day 28) during split-belt treadmill walking. Early adaptation is quantified using relative step length asymmetry (SLA), calculated from strides 6 to 30 following split-belt onset. SLA is computed from three-dimensional motion capture and force data as the difference between step lengths of the legs, normalized to total stride length: SLA = (Step Length\_fast - Step Length\_slow) / (Step Length\_fast + Step Length\_slow). This yields a unitless measure of asymmetry. The outcome measure is the difference in SLA between visits (training session 2 - training session 1). Larger values reflect faster adaptation at training session 2, consistent with retention of prior learning.

  Training session 1 (day 1), training session 2 (day 28)

• Rate of Step Length Asymmetry Adaptation

  Step length asymmetry during early adaptation, representing the rate of adaptation. Early adaptation is quantified using relative step length asymmetry (SLA), calculated from strides 6 to 30 following split-belt onset. SLA is computed from three-dimensional motion capture and force data as the difference between step lengths of the legs, normalized to total stride length: SLA = (Step Length\_fast - Step Length\_slow) / (Step Length\_fast + Step Length\_slow). This yields a unitless measure of asymmetry. The outcome measure is the difference in early adaptation SLA during TENS ON compared to TENS OFF. Values closer to zero reflect faster adaptation.This analysis was performed only on data from each participant's first visit to avoid known effects of increased adaptation rate (learning) during subsequent exposures.

  Training session 1 (day 1)

Study Arms (2)

Split-belt Treadmill Training without TENS

SHAM COMPARATOR

During this arm, participants will perform split-belt treadmill training with sensory stimulation equipment outfitted but not active during all adaptation sessions.

Behavioral: Split-belt Treadmill

Split-belt Treadmill Training with TENS

EXPERIMENTAL

During this arm, participants will perform split-belt treadmill training with active sensory stimulation occuring simultaneously during all adaptation sessions.

Behavioral: Split-belt Treadmill; Device: Transcutaneous Electrical Nerve Stimulation (TENS)

Interventions

Split-belt Treadmill BEHAVIORAL

Split-belt treadmill training, where the speed of each leg is controlled independently has been shown to create gait adaptation where the coordination of each leg is altered, creating improved gait symmetry for people with walking impairments.

Split-belt Treadmill Training with TENS; Split-belt Treadmill Training without TENS

Transcutaneous Electrical Nerve Stimulation (TENS) DEVICE

TENS is a form of nerve stimulation that stimulates at a frequency below motor threshold, targeting activation of sensory receptors, such as muscle spindles. Electrodes that create this stimulation will be placed on the skin superficial to the muscle bellies of the tibialis anterior and rectus femoris.

Split-belt Treadmill Training with TENS

Eligibility Criteria

• Age: 18 Years - 86 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of relapsing remitting multiple sclerosis OR a neurotypical adult (ages 18-86)
• Not experiencing an active relapse
• Able to stand and walk without an assistive device
• Able to walk for three tenths of a mile without stopping to rest

You may not qualify if:

• Unable to walk for three tenths of a mile without assistance
• Musculoskeletal injury in past 6 months
• Lower extremity surgery in past 6 months
• Unable to abstain from medications that impair balance
• Currently pregnant
• History of traumatic brain injury
• History of vestibular disease
• History of any other balance impairment unrelated to multiple sclerosis

Sponsors & Collaborators

• Colorado State University: lead
• National Multiple Sclerosis Society: collaborator

Study Sites (1)

The Sensorimotor Neuroimaging Laboratory

Fort Collins, Colorado, 80523, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Transcutaneous Electric Nerve Stimulation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Physical Therapy Modalities; Rehabilitation; Analgesia; Anesthesia and Analgesia

Results Point of Contact

• Title: Dr. Brett Fling
• Organization: Colorado State University

brett.fling@colostate.edu

(970) 491-3451

Study Officials

• Brett W Fling, Ph.D.

  Colorado State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 12, 2023
• First Posted: May 26, 2023
• Study Start: November 28, 2023
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: July 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)