Multiple SclerosisNCT05878873
The Neural Mechanisms of Split-belt Treadmill Adaptation in People With Multiple Sclerosis
A study testing Split-belt Treadmill and Transcutaneous Electrical Nerve Stimulation (TENS) in people with Multiple Sclerosis, run by Colorado State University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 86 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Split-belt Treadmill and Transcutaneous Electrical Nerve Stimulation (TENS)
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Nov 2023to 30 Jun 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 86 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
The Sensorimotor Neuroimaging Laboratory
Fort Collins, Colorado, 80523
About this study
Official title: The Neural Underpinnings and the Impact of Wearable Sensory Stimulation During Split-belt Treadmill Adaptation in People With Multiple Sclerosis
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:
Read more
- 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.
Read the detailed description
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.
- Conditions
- Multiple Sclerosis
- Being tested
- Split-belt Treadmill, Transcutaneous Electrical Nerve Stimulation (TENS)
- Keywords
- split-belt treadmill, adaptation, multiple sclerosis, functional near-infrared spectroscopy, cortical activation, gait asymmetry, locomotion, sensorimotor control
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Split-belt TreadmillBehavioural
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Behavioral: Split-belt Treadmill; Device: Transcutaneous Electrical Nerve Stimulation (TENS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: Training session 1 (day 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2023
- Study start28 Nov 2023
- Primary completion30 Jun 2024
- Study completion30 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Colorado State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Responsible party
- Principal investigator, Brett Fling, Colorado State University
- Investigators
- Brett W Fling, Ph.D., Principal investigator, Colorado State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05878873
- Sponsor's protocol ID
- 1664
- Status last verified
- Jun 2025
- First submitted
- 12 May 2023
- Last updated
- 3 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: The data will not publicly available due to participant privacy.
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Neural Underpinnings and the Impact of Wearable Sensory Stimulation During Split-belt Treadmill Adaptation in People With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT05878873
- Acronym / sponsor ID
- 1664
- Conditions
- Multiple Sclerosis
- Keywords
- split-belt treadmill, adaptation, multiple sclerosis, functional near-infrared spectroscopy, cortical activation, gait asymmetry, locomotion, sensorimotor control
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Colorado State UniversityUniversity, hospital or other
- Collaborators
- National Multiple Sclerosis Society
- Study start
- 28 Nov 2023 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 26 May 2023 (actual)
- Results
- Posted 3 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Split-belt Treadmill Training without TENS | Sham comparator | Behavioral: Split-belt TreadmillDuring this arm, participants will perform split-belt treadmill training with sensory stimulation equipment outfitted but not active during all adaptation sessions. |
| Split-belt Treadmill Training with TENS | Experimental | Behavioral: Split-belt Treadmill, Device: Transcutaneous Electrical Nerve Stimulation (TENS)During this arm, participants will perform split-belt treadmill training with active sensory stimulation occuring simultaneously during all adaptation sessions. |
Who may qualify
- Ages
- 18 to 86 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Split-belt TreadmillSplit-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. | Behavioural | Split-belt Treadmill Training with TENS, Split-belt Treadmill Training without TENS |
| Transcutaneous Electrical Nerve Stimulation (TENS)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. | Device | Split-belt Treadmill Training with TENS |
Primary outcome
Change in Cortical Activation
Time frame: 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 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).
Change in Adaptation Savings
Time frame: 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 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.
Rate of Step Length Asymmetry Adaptation
Time frame: 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 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. The data will not publicly available due to participant privacy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brett W Fling, Ph.D. principal investigator
Colorado State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Split-belt Treadmill and Transcutaneous Electrical Nerve Stimulation (TENS) in people with Multiple Sclerosis, run by Colorado State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cortical Activation (time frame: Training session 1 (day 1), training session 2 (day 28)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.