An interventional study of Split-belt Treadmill and Transcutaneous Electrical Nerve Stimulation (TENS) in Multiple Sclerosis, sponsored by Colorado State University. Completed at 1 site in United States. Open to participants aged 18 Years to 86 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-07-03.
Sponsored by Colorado State University · Not applicable, Interventional, and Treatment
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:
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.
Most people with MS (PwMS) experience significant gait asymmetries between the two legs leading to an increased risk of falls and musculoskeletal injury. The objective of this study is to investigate the neural mechanisms of gait adaptation and the effects of transcutaneous electrical nerve stimulation (TENS) on adaptability during split-belt treadmill training in PwMS. Our hypothesis is that TENS will strengthen sensorimotor integration via amplified afferent signaling, thereby enhancing adaptation, and further improving gait symmetry chronically. Functional near-infrared spectroscopy (fNIRS) will be used during a split-belt treadmill training paradigm to assess cortical activation during gait adaptation. Additionally, the effect of split-belt treadmill training coupled with TENS on gait adaptability in PwMS will be tested with experimental and a sham TENS split-belt treadmill sessions. Cortical activation and the effect of TENS on gait adaptability will be compared between young neurotypical adults and PwMS to assess differences that can be attributed to multiple sclerosis.
3,460 studies on the registry are indexed under Multiple Sclerosis; 661 are open to participants now.
This study's enrollment of 51 is close to the median of 50 across 2,342 interventional studies indexed under Multiple Sclerosis.
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Of its 5 completed or terminated interventional studies of FDA-regulated products, 3 (60%) have results posted.
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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
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)
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.
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.
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).
Time frame: 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.
Time frame: 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.
Time frame: Training session 1 (day 1)
| Milestone | Split-belt Treadmill Training With TENS First | Split-belt Treadmill Training With TENS Second |
|---|---|---|
| Started | 24 | 27 |
| People with multiple sclerosis started: | 15 | 16 |
| People with multiple sclerosis completed: | 13 | 16 |
| Healthy controls started: | 9 | 11 |
| Healthy controls completed: | 9 | 11 |
| Completed | 22 | 27 |
| Not completed | 2 | 0 |
| Withdrew: Lost to follow-up | 2 | 0 |
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).
| Unitless GLM beta weight (HbO) | Split-belt Treadmill Training Without TENS | Split-belt Treadmill Training With TENS |
|---|---|---|
| People with Multiple Sclerosis | 0.054 ± 0.021 | -0.024 ± 0.021 |
| Healthy Controls | 0.074 ± 0.025 | -0.016 ± 0.025 |
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.
| Unitless Relative Step Length Asymmetry | Split-belt Treadmill Training With TENS First | Split-belt Treadmill Training With TENS Second |
|---|---|---|
| People with Multiple Sclerosis | 0.0032 ± 0.0103 | 0.0451 ± 0.0096 |
| Healthy Controls | 0.0221 ± 0.0124 | 0.0278 ± 0.0112 |
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.
| Unitless Relative Step Length Asymmetry | Split-belt Treadmill Training Without TENS | Split-belt Treadmill Training With TENS |
|---|---|---|
| People with Multiple Sclerosis | -0.090 ± 0.012 | -0.088 ± 0.013 |
| Healthy Controls | -0.095 ± 0.014 | -0.103 ± 0.016 |
Collected over Adverse events were monitored during each study visit (visit 1 at day 1 and visit 2 at day 28) and between visits. Participants were not followed after study completion.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Split-belt Treadmill Training With TENS: People With Multiple Sclerosis | 0/29 (0%) | 0/29 (0%) | 0/29 (0%) |
| Split-belt Treadmill Training Without TENS: People With Multiple Sclerosis | 0/29 (0%) | 0/29 (0%) | 0/29 (0%) |
| Split-belt Treadmill Training With TENS: Healthy Controls | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) |
| Split-belt Treadmill Training Without TENS: Healthy Controls | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) |
This population contained 28 people with multiple sclerosis and 20 healthy controls.
| Age, Continuous(years) | Split-belt Treadmill Training With TENS First | Split-belt Treadmill Training With TENS Second | Total |
|---|---|---|---|
| People with Multiple Sclerosis | 55.5 ± 9.1 | 52.2 ± 11.6 | 53.7 ± 10.5 |
| Healthy Controls | 57.3 ± 11.9 | 50.9 ± 15.5 | 53.8 ± 14.0 |
| Sex: Female, Male(Participants) | Split-belt Treadmill Training With TENS First | Split-belt Treadmill Training With TENS Second | Total |
|---|---|---|---|
| People with Multiple Sclerosis — Female | 8 | 11 | 19 |
| People with Multiple Sclerosis — Male | 5 | 4 | 9 |
| Healthy Controls — Female | 6 | 6 | 12 |
| Healthy Controls — Male | 3 | 5 | 8 |
| Ethnicity (NIH/OMB)(Participants) | Split-belt Treadmill Training With TENS First | Split-belt Treadmill Training With TENS Second | Total |
|---|---|---|---|
| People with Multiple Sclerosis — Hispanic or Latino | 1 | 0 | 1 |
| People with Multiple Sclerosis — Not Hispanic or Latino | 12 | 15 | 27 |
| People with Multiple Sclerosis — Unknown or Not Reported | 0 | 0 | 0 |
| Healthy Controls — Hispanic or Latino | 0 | 0 | 0 |
| Healthy Controls — Not Hispanic or Latino | 9 | 11 | 20 |
| Healthy Controls — Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Split-belt Treadmill Training With TENS First | Split-belt Treadmill Training With TENS Second | Total |
|---|---|---|---|
| People with Multiple Sclerosis — American Indian or Alaska Native | 0 | 0 | 0 |
| People with Multiple Sclerosis — Asian | 0 | 0 | 0 |
| People with Multiple Sclerosis — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| People with Multiple Sclerosis — Black or African American | 0 | 1 | 1 |
| People with Multiple Sclerosis — White | 13 | 14 | 27 |
| People with Multiple Sclerosis — More than one race | 0 | 0 | 0 |
| People with Multiple Sclerosis — Unknown or Not Reported | 0 | 0 | 0 |
| Healthy Controls — American Indian or Alaska Native | 0 | 0 | 0 |
| Healthy Controls — Asian | 0 | 0 | 0 |
| Healthy Controls — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Healthy Controls — Black or African American | 0 | 0 | 0 |
| Healthy Controls — White | 9 | 11 | 20 |
| Healthy Controls — More than one race | 0 | 0 | 0 |
| Healthy Controls — Unknown or Not Reported | 0 | 0 | 0 |
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Plan to share: No — The data will not publicly available due to participant privacy.
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Colorado State University