NCT05878873

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

Completed NA Results posted Last updated 3 July 2025

What this trial tests

NA trial testing Split-belt Treadmill in Multiple Sclerosis in 51 participants. Completed in 30 June 2024.

Timeline

28 November 2023

Primary endpoint
30 June 2024

30 June 2024

Quick facts

Lead sponsor	Colorado State University
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	single
Primary purpose	treatment
Enrollment	51
Start date	28 November 2023
Primary completion	30 June 2024
Estimated completion	30 June 2024
Sites	1 location across United States

Drugs / interventions tested

• Split-belt Treadmill
• Transcutaneous Electrical Nerve Stimulation (TENS)

Conditions studied

• Multiple Sclerosis — all drugs for Multiple Sclerosis →

Sponsor

Colorado State University

Who can join

Adults 18 to 86, any sex, with Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Cortical Activation Primary · Training session 1 (day 1), training session 2 (day 28)

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 e

People with Multiple Sclerosis

Group	Value	95% CI
Split-belt Treadmill Training Without TENS	0.054	± 0.021
Split-belt Treadmill Training With TENS	-0.024	± 0.021

Healthy Controls

Group	Value	95% CI
Split-belt Treadmill Training Without TENS	0.074	± 0.025
Split-belt Treadmill Training With TENS	-0.016	± 0.025

Change in Adaptation Savings Primary · Training session 1 (day 1), training session 2 (day 28)

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

People with Multiple Sclerosis

Group	Value	95% CI
Split-belt Treadmill Training With TENS First	0.0032	± 0.0103
Split-belt Treadmill Training With TENS Second	0.0451	± 0.0096

Healthy Controls

Group	Value	95% CI
Split-belt Treadmill Training With TENS First	0.0221	± 0.0124
Split-belt Treadmill Training With TENS Second	0.0278	± 0.0112

Rate of Step Length Asymmetry Adaptation Primary · Training session 1 (day 1)

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

People with Multiple Sclerosis

Group	Value	95% CI
Split-belt Treadmill Training Without TENS	-0.090	± 0.012
Split-belt Treadmill Training With TENS	-0.088	± 0.013

Healthy Controls

Group	Value	95% CI
Split-belt Treadmill Training Without TENS	-0.095	± 0.014
Split-belt Treadmill Training With TENS	-0.103	± 0.016

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Transcutaneous electrical nerve stimulation enhances locomotor adaptation savings in people with multiple sclerosis.
   Hagen AC, Whittier TT, Stephens JA, Fling BW. · · 2025 · PMID 40636812 · DOI 10.1093/braincomms/fcaf255