Multiple SclerosisNCT06264336
Effects of High-intensity Gait Training on Fatigue, Gait, and Neuroplasticity in People With Multiple Sclerosis
A study testing treadmill training in people with Multiple Sclerosis, run by University of Illinois Chicago at 1 site in United States.
Trial summary
Nearly 1 million individuals in the United States have multiple sclerosis, which causes fatigue and problems with walking. Fatigue and walking problems are poorly treated, but exercise training, particularly high-intensity walking exercise, may help. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- treadmill training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2024to 31 Mar 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥21 years
- Multiple sclerosis diagnosis
- Stable disease-modifying therapy (DMT) over the past 6 months
- Walking dysfunction (i.e., abnormal gait pattern, Expanded Disability Status Scale (EDSS) score of 4-6.5, and/or Patient-determined disease steps (PDDS) score of 3-6)
- Able to walk for 6 minutes at self-paced speed. Handheld assistive device is acceptable.
- Symptomatic fatigue (Fatigue Severity Score ≥ 4)
Who cannot join
- Adults unable to consent
- Pregnant women
- Prisoners
- Multiple sclerosis relapse within the last 30 days
- Other neurological disorders besides multiple sclerosis
- Cardiorespiratory or metabolic diseases (e.g., cardiac arrhythmia, uncontrolled hypertension or diabetes, chronic emphysema)
Show all 16Show fewer
- Significant cognitive or communication impairment (Mini-Mental State Examination (MMSE)<21), which could impede the understanding of the purpose of procedures of the study or prevent the patient from performing the ankle-tracking task.
- Severe osteoporosis
- Failure to pass the graded exercise stress test
- Implanted cardiac pacemaker
- Metal implants in the head or face
- Unexplained, recurring headaches
- History of seizures or epilepsy
- Currently under medication that could increase motor excitability and lower seizure threshold
- Skull abnormalities or fractures
- Concussion within the last 6 months
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois Chicago
Chicago, Illinois, 60612
About this study
Nearly 1 million individuals in the United States have multiple sclerosis, which causes fatigue and problems with walking. Fatigue and walking problems are poorly treated, but exercise training, particularly high-intensity walking exercise, may help. This provide insight into whether high-intensity walking exercise can improve fatigue and walking problems in people with multiple sclerosis, which could improve quality of life and reduce economic burden.
Read the detailed description
Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system with a prevalence of nearly 1 million adults in the US. The pathophysiology of this disease results in two of the hallmark features of MS, namely symptomatic fatigue and walking impairment. These two features of MS are inter-related as symptomatic fatigue is often a driver of declines in walking and worsening of disability over time, and both compromise quality of life and independence. To date, fatigue and walking impairment are poorly managed through conventional disease modifying medications or rehabilitation therapy in MS.
One approach for improving fatigue and walking in MS is an appropriate dose of exercise training. Current recommendations of 30 min/day 2 days/week of low to moderate exercise training can improve symptomatic fatigue, aerobic capacity, strength, and walking endurance, and other symptoms in people with MS. This prescription is often delivered using moderate-intensity, continuous training (MCT) walking. However, improvements in fatigue and walking outcomes have been small, suggesting that MCT may not be the optimal approach. In people with stroke, high intensity, interval-based walking exercise has provided a greater stimulus than MCT for improving outcomes, but this approach has not been researched in MS.
There are a few field-wide limitations of research on exercise training, fatigue, and walking outcomes in MS. Often, researchers have (a) enrolled people with MS regardless of symptomatic fatigue and/or walking dysfunction, and this yields floor effects in outcomes and prevents conclusions on exercise as a treatment approach; (b) included people with mild disability, but not moderate or severe disability; and (c) applied exercise modalities not based on the principle of specificity (i.e., using walking training to improve fatigue and walking impairment). This project overcomes these field-wide limitations and compares effects of moderate and high intensity treadmill training on symptomatic fatigue and walking in people with MS with elevated fatigue and walking dysfunction.
- Conditions
- Multiple Sclerosis
- Being tested
- treadmill training
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
treadmill trainingBehavioural
Participants will undergo 12 sessions (4 weeks, 3 sessions/week) of treadmill training. During each session, participants will walk for 40 min. with 5 min. of warmup and cooldown at 50% of maximal walking speed (tested each week) with 30 min. of training interposed. The type of training will be determined by the assigned treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| High-intensity interval treadmill training | Experimental | Walking with high intensity intervals interspersed. Receives: Behavioral: treadmill training |
| Moderate-intensity continuous treadmill training | Active comparator | Continuous walking at a moderate intensity Receives: Behavioral: treadmill training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptomatic fatigue
Change in symptomatic fatigue from pre to post training. Assessed by the Fatigue Severity Scale (FSS); scores range between 1 (min) and 7 (max), higher scores reflect greater fatigue severity.
Measured: Immediately (within 1 week) before and after training
Walking speed
Change in walking speed will be measured with the 10-m walk test. This will be quantified as the average of 3 trials a comfortable and maximal speeds. Higher values represent faster walking speeds
Measured: Immediately (within 1 week) before and after training
Corticomotor excitability
Transcranial magnetic stimulation (TMS) will be used to measure change in contralateral and ipsilateral corticomotor excitability of the paretic tibialis anterior. TMS will be applied at different intensities, and the response (motor evoked potential) is measured in the paretic TMS. Corticomotor excitability will be measured as the slope of the input output curve (intensity vs. response). Higher values represent greater corticomotor excitability.
Measured: Immediately (within 1 week) before and after training
Secondary outcomes (5)
Fatigue impact
Change in the impact of fatigue on physical, cognitive, and psychosocial functioning will be measured from pre to post training. Assessed with the Modified Fatigue Impact Scale (MFIS); scores range between 0 (min) and 84 (max), higher scores reflect greater impact of fatigue.
Measured: Immediately (within 1 week) before and after training
Walking endurance
Change in walking endurance will be assessed as the distance covered during the 6-minute walk test (6mWT). Higher values represent greater walking endurance.
Measured: Immediately (within 1 week) before and after training
Aerobic capacity
Cardiopulmonary exercise tests will be performed on a motorized treadmill following an individualized protocol using standard procedures. Measures relating to peak oxygen consumption (VO2 max) will be calculated to quantify aerobic capacity. Higher values represent greater aerobic capacity.
Measured: Immediately (within 1 week) before and after training
Visual processing speed
Assessed by the Symbol Digit Modalities Test (SDMT). Participants will verbally identify digit-symbol pairings as quickly as possible in response to a series of unpaired symbols displayed on screen. The outcome is the total number of correct responses in 30, 60 and 90 seconds. Higher scores represent greater visual processing speed.
Measured: Immediately (within 1 week) before and after training
Verbal learning and memory
Assessed by the California Verbal Learning Test II (CVLT-II). Participants will be read aloud 16 words and immediately recall as many words as possible, in any order, for each of the five trials. The total score out of 80 will be calculated by summing the number of correct responses from each trial (T1 to T5). Higher scores represent greater verbal learning and memory.
Measured: Immediately (within 1 week) before and after training
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2024
- Study start1 Mar 2024
- Primary completion31 Mar 2026
- Study completion31 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brice Cleland, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06264336
- Sponsor's protocol ID
- UIC AHS Pilot 2024
- Status last verified
- May 2026
- First submitted
- 1 Feb 2024
- Last updated
- 7 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All underlying data for this study will be deidentified and then will be shared.
Publications
Cleland BT, Jeng B, Brown N, Motl RW, Madhavan S. Feasibility and efficacy of peak-velocity interval training vs. moderate-intensity walking training in people with multiple sclerosis with severe fatigue and walking impairment: A pilot randomized controlled trial. Mult Scler Relat Disord. 2026 Feb;106:106930. doi: 10.1016/j.msard.2025.106930. Epub 2025 Dec 12.
PubMed 41418486
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of High-intensity Gait Training on Fatigue, Gait, and Neuroplasticity in People With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT06264336
- Acronym / sponsor ID
- UIC AHS Pilot 2024
- Conditions
- Multiple Sclerosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 31 Mar 2026 (actual)
- Study completion
- 31 Mar 2026 (actual)
- First posted
- 16 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Nearly 1 million individuals in the United States have multiple sclerosis, which causes fatigue and problems with walking. Fatigue and walking problems are poorly treated, but exercise training, particularly high-intensity walking exercise, may help. This provide insight into whether high-intensity walking exercise can improve fatigue and walking problems in people with multiple sclerosis, which could improve quality of life and reduce economic burden.
Detailed description
Multiple sclerosis (MS) is an immune-mediated, neurodegenerative disease of the central nervous system with a prevalence of nearly 1 million adults in the US. The pathophysiology of this disease results in two of the hallmark features of MS, namely symptomatic fatigue and walking impairment. These two features of MS are inter-related as symptomatic fatigue is often a driver of declines in walking and worsening of disability over time, and both compromise quality of life and independence. To date, fatigue and walking impairment are poorly managed through conventional disease modifying medications or rehabilitation therapy in MS.
One approach for improving fatigue and walking in MS is an appropriate dose of exercise training. Current recommendations of 30 min/day 2 days/week of low to moderate exercise training can improve symptomatic fatigue, aerobic capacity, strength, and walking endurance, and other symptoms in people with MS. This prescription is often delivered using moderate-intensity, continuous training (MCT) walking. However, improvements in fatigue and walking outcomes have been small, suggesting that MCT may not be the optimal approach. In people with stroke, high intensity, interval-based walking exercise has provided a greater stimulus than MCT for improving outcomes, but this approach has not been researched in MS.
There are a few field-wide limitations of research on exercise training, fatigue, and walking outcomes in MS. Often, researchers have (a) enrolled people with MS regardless of symptomatic fatigue and/or walking dysfunction, and this yields floor effects in outcomes and prevents conclusions on exercise as a treatment approach; (b) included people with mild disability, but not moderate or severe disability; and (c) applied exercise modalities not based on the principle of specificity (i.e., using walking training to improve fatigue and walking impairment). This project overcomes these field-wide limitations and compares effects of moderate and high intensity treadmill training on symptomatic fatigue and walking in people with MS with elevated fatigue and walking dysfunction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High-intensity interval treadmill training | Experimental | Behavioral: treadmill trainingWalking with high intensity intervals interspersed. |
| Moderate-intensity continuous treadmill training | Active comparator | Behavioral: treadmill trainingContinuous walking at a moderate intensity |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥21 years
- Multiple sclerosis diagnosis
- Stable disease-modifying therapy (DMT) over the past 6 months
- Walking dysfunction (i.e., abnormal gait pattern, Expanded Disability Status Scale (EDSS) score of 4-6.5, and/or Patient-determined disease steps (PDDS) score of 3-6)
- Able to walk for 6 minutes at self-paced speed. Handheld assistive device is acceptable.
Key exclusion criteria (16 listed)
- Adults unable to consent
- Pregnant women
- Prisoners
- Multiple sclerosis relapse within the last 30 days
- Other neurological disorders besides multiple sclerosis
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 |
|---|---|---|
| treadmill trainingParticipants will undergo 12 sessions (4 weeks, 3 sessions/week) of treadmill training. During each session, participants will walk for 40 min. with 5 min. of warmup and cooldown at 50% of maximal walking speed (tested each week) with 30 min. of training interposed. The type of training will be determined by the assigned treatment arm. | Behavioural | High-intensity interval treadmill training, Moderate-intensity continuous treadmill training |
Primary outcome
Symptomatic fatigue
Time frame: Immediately (within 1 week) before and after training
Change in symptomatic fatigue from pre to post training. Assessed by the Fatigue Severity Scale (FSS); scores range between 1 (min) and 7 (max), higher scores reflect greater fatigue severity.
Walking speed
Time frame: Immediately (within 1 week) before and after training
Change in walking speed will be measured with the 10-m walk test. This will be quantified as the average of 3 trials a comfortable and maximal speeds. Higher values represent faster walking speeds
Corticomotor excitability
Time frame: Immediately (within 1 week) before and after training
Transcranial magnetic stimulation (TMS) will be used to measure change in contralateral and ipsilateral corticomotor excitability of the paretic tibialis anterior. TMS will be applied at different intensities, and the response (motor evoked potential) is measured in the paretic TMS. Corticomotor excitability will be measured as the slope of the input output curve (intensity vs. response). Higher values represent greater corticomotor excitability.
5 secondary outcomes
Fatigue impact
Time frame: Immediately (within 1 week) before and after training
Walking endurance
Time frame: Immediately (within 1 week) before and after training
Aerobic capacity
Time frame: Immediately (within 1 week) before and after training
Visual processing speed
Time frame: Immediately (within 1 week) before and after training
Verbal learning and memory
Time frame: Immediately (within 1 week) before and after training
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
- Derived from this study: PubMed 41418486Cleland BT, Jeng B, Brown N, Motl RW, Madhavan S. Feasibility and efficacy of peak-velocity interval training vs. moderate-intensity walking training in people with multiple sclerosis with severe fatigue and walking impairment: A pilot randomized controlled trial. Mult Scler Relat Disord. 2026 Feb;106:106930. doi: 10.1016/j.msard.2025.106930. Epub 2025 Dec 12.
- Individual participant dataSharing planned: Yes. All underlying data for this study will be deidentified and then will be shared.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing treadmill training in people with Multiple Sclerosis, run by University of Illinois Chicago 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 6 inclusion and 16 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 7 May 2026. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Symptomatic fatigue (time frame: Immediately (within 1 week) before and after training). 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?
On the ClinicalTrials.gov record for NCT06264336, which also lists 1 linked publication.
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 7 May 2026.