Walking Fatigability and Brain Activity in People With Multiple Sclerosis

NCT06672484 | Active Not Recruiting

• 1 other identifier: B1152024000007
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

Walking fatigability is a motor impairment happening in approximately 43.5% of people with multiple sclerosis (pwMS). Walking fatigability is defined as a decrease in 10% of distance walked, comparing the first minute with the last minute of the 6-minute walking test (6MWT), which one may call distance walking fatigability. More recently, our research group has found that walking fatigability manifests also in terms of gait quality, with different gait characteristics affected from patient to patient, suggesting that different gait profiles might be observed for walking fatigability. One possible explanation for the walking fatigability motor impairment is the lower capacity or neural reserve of pwMS to sustain optimal levels of cortical activity to either maintain performance (i.e., distance walked) or gait quality. The study proposes two research questions. Both part A and B are observational studies. The study includes 70 pwMS and 30 healthy controls. The study consists of 3 tests. The clinical assessment session will be composed of responses to different questionnaires, while parts A and B comprehend walking overground (part A) or on fixed-speed treadmill (part B). Part A Session 1 (1 hour and 30minutes, including equipment preparation and rest time). First, anthropometric characteristics and measurements of force, spasticity, cognition, walking speed, and performance foot tap test will be performed. For cortical activity measurement of the prefrontal cortex, supplementary motor area, premotor cortex, and primary motor cortex, a functional Nears-infrared Spectroscopy (fNIRS) will be positioned in the participant\'s head. Wearable sensors will be positioned in a pre-defined body position for the measurement of gait characteristics. Both gait characteristics and cortical brain activation will be measured concomitantly during fast and comfortable speed short walking (10 trials of 15 seconds with 25-30 seconds standing still resting periods between trials, in a block design) before and after and during a prolonged walking (6-minute walking test (6MWT)) protocols. A resting period of 20 minutes will be provided to the participants before the beginning of the 6MWT. Part B. Participants who participated in Part A will be invited to participate in Part B. This study also consists of a single visit that is 1 hour and 30 minutes long (preparation and assessment included). The participants will be asked to walk on an immersive treadmill in two fixed-speed conditions (relative to 80% and 50% of the Timed 25-foot Walking test) while infrared cameras will record the reflective markers position. Forty minutes of rest will be provided to the participants between the fixed-speed conditions.

Conditions

Multiple Sclerosis; Healthy

Keywords

Multiple sclerosis; walking; fatigue; fatigability; gait; cortical activity; brain activity

Outcome Measures

Primary Outcomes (13)

• Range of Motion (hip, knee and ankle joints) during the gait cycle

  The angle of the hip, knee, and ankle joints in the sagittal (flexion-extension), coronal (adduction-abduction), and transversal (rotation) plans during the gait cycle

  Day 2 and day 3

• Toe-Off angle

  The plantar flexion of the foot in the last moment of contact of the feet with the floor

  Day 2 and day 3

• Foot Strike angle

  The dorsiflexion of the feet in the heel strike

  Day 2 and day 3

• Relative concentration of oxyhemoglobin and deoxyhemoglobin

  The cortical brain activation will be obtained through functional near-infrared spectroscopy (fNIRS). The fNIRS measures the relative concentration of oxyhemoglobin and deoxyhemoglobin in the brain tissue, more specifically, in the brain cortex. The following brain regions will be measured: * Frontopolar cortex (Broadman area 10) * Dorsolateral prefrontal cortex (Broadman 9 and 46) * Primary motor cortex (Broadman area 4) * Supplementary motor area (Broadman area 6) * Premotor cortex (Broadman area 6)

  Day 2

• Gait Speed

  The anteroposterior distance, divided by the gait cycle duration (two subsequent heel strikes of the same leg).

  Day 2 and day 3

• Cadence

  Number of steps made per minute (both legs)

  Day 2 and day 3

• Step Duration

  The duration from the heel strike of a leg with the heel strike of the contralateral leg

  Day 2 and day 3

• Step Duration variability

  The coefficient of variation calculated from the step duration variable

  Day 2 and day 3

• Ground reaction force

  It is the amount of force produced against the floor by a person. It will measured in the three directions: vertical, anteroposterior, and medial-lateral.

  Day 3

• Fatigability index

  A fatigability index will be applied for all gait parameters for the 6-minute walking test and the treadmill walking listed in accordance with the following sentence: fatigability index: ((gait parameters at minute n- gait parameter at minute 1)/gait parameter at minute 1)\*100.

  Day 2 and day 3

• Perception of gait quality change (PGQC)

  It is a questionnaire to measure the capacity of the person to perceive changes in his/her gait after walking for a prolonged time. Here, this questionnaire is asked after the 6-minute walking test (6MWT). The questionnaire is in a Likert-type score, ranging from -3 (very much worse) to 3 (very much improved).

  Day 2 and day 3

• Distance walked index (DWI)

  The distance walked index (DWI) will be applied to the distance walked in each minute of the 6-minute walking test using the following formula: DWI(%) = ((distance walked at minute n- distance walked at minute 1)/ distance walked at minute 1)\*100

  Day 2

• 6-minutes walking test

  The total distance and the distance walked, in meters, minute-by-minute will be recorded during the 6-minutes walking test.

  Day 2

Secondary Outcomes (16)

• Joint power during the gait cycle

  Day 3

• Momentum

  Day 3

• Falls Efficacy Scale International (FES-I)

  Day 1

• Multiple Sclerosis Walking Scale (MSWS-12)

  Day 1

• Pittsburgh Fatigability Scale (PFS)

  Day 1

Other Outcomes (4)

• Lyapunov Exponent

  Day 2

• Double Support

  Day 2 and day 3

• Patients determined disease steps (PDDS)

  Day 1

Study Arms (2)

Multiple Sclerosis

People presenting with multiple sclerosis diagnosis according to the 2017 revisions of the Mcdonald's criteria.

Healthy people

Inclusion criteria for healthy controls (part A and B): inclusion of age between 18 and 65 years old, sex- and age-matched on a group level.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the Flemish MS rehabilitation centers Melsbroek (NMSC) and Overpelt (Noorderhart RMSC), as well as the REVAL research center in UHasselt. Information flyers will be distributed in the centers and via information placed on the website and social media of REVAL and the Flemish MS society. We will search age and sex-matching subjects for the healthy controls, considering a 5-year range per subject.

You may qualify if:

• age between 18 and 65 years old
• a diagnosis of MS (2017 revisions of the McDonalds criteria) with EDSS 1 up to 6.5 (part A) and with EDSS 1 up to 5.5 (part B) OR minimal punctuation of 2 in the MSWS-12 for one of the items: 7, 10, 11, and 12 (for pwMS)
• no relapses 1 month preceding the start of the study (for pwMS)
• ability to walk for 6 minutes without rest

You may not qualify if:

• Cognitive impairment hindering understanding of study instructions,
• Pregnancy
• Musculoskeletal disorders in the lower limbs that are not related to MS.
• PwMS needing an assistive device to walk can not be included in part B given safety reasons.

Sponsors & Collaborators

• National MS Center Melsbroek: collaborator
• Revalidatie & MS Centrum Overpelt: collaborator
• Hasselt University: lead

Study Sites (3)

University of Hasselt

Diepenbeek, Limburg, 3500, Belgium

Location

National MS Melsbroek

Melsbroek, 1820, Belgium

Location

Noorderhart Rehabilitation & MS centre

Overpelt, 3900, Belgium

Location

Related Publications (14)

• Santinelli FB, Abasiyanik Z, Dalgas U, Ozakbas S, Severijns D, Gebara B, Maamagi H, Romberg A, Rasova K, Santoyo-Medina C, Ramari C, Leone C, Feys P. Prevalence of distance walking fatigability in multiple sclerosis according to MS phenotype, disability severity and walking speed. Ann Phys Rehabil Med. 2025 Feb;68(1):101887. doi: 10.1016/j.rehab.2024.101887. Epub 2024 Dec 9. No abstract available.

  PMID: 39657457 BACKGROUND

• Van Geel F, Veldkamp R, Severijns D, Dalgas U, Feys P. Day-to-day reliability, agreement and discriminative validity of measuring walking-related performance fatigability in persons with multiple sclerosis. Mult Scler. 2020 Nov;26(13):1785-1789. doi: 10.1177/1352458519872465. Epub 2019 Sep 9.

  PMID: 31496362 BACKGROUND

• Van Geel F, Hvid LG, Van Noten P, Eijnde BO, Dalgas U, Feys P. Is maximal muscle strength and fatigability of three lower limb muscle groups associated with walking capacity and fatigability in multiple sclerosis? An exploratory study. Mult Scler Relat Disord. 2021 May;50:102841. doi: 10.1016/j.msard.2021.102841. Epub 2021 Feb 10.

  PMID: 33621946 BACKGROUND

• Strzok S, Cleanthous S, Pompilus F, Cano SJ, Marquis P, Cohan S, Goldman MD, Kresa-Reahl K, Petrillo J, Castrillo-Viguera C, Cadavid D, Chen SY. Development of a gait module to complement the 12-item Multiple Sclerosis Walking Scale: a mixed methods study. Mult Scler J Exp Transl Clin. 2018 Jun 26;4(2):2055217318783766. doi: 10.1177/2055217318783766. eCollection 2018 Apr-Jun.

  PMID: 30090638 BACKGROUND

• Sehle A, Mundermann A, Starrost K, Sailer S, Becher I, Dettmers C, Vieten M. Objective assessment of motor fatigue in Multiple Sclerosis using kinematic gait analysis: a pilot study. J Neuroeng Rehabil. 2011 Oct 26;8:59. doi: 10.1186/1743-0003-8-59.

  PMID: 22029427 BACKGROUND

• Sato S, Lim J, Miehm JD, Buonaccorsi J, Rajala C, Khalighinejad F, Ionete C, Kent JA, van Emmerik REA. Rapid foot-tapping but not hand-tapping ability is different between relapsing-remitting and progressive multiple sclerosis. Mult Scler Relat Disord. 2020 Jun;41:102031. doi: 10.1016/j.msard.2020.102031. Epub 2020 Feb 27.

  PMID: 32172213 BACKGROUND

• Santinelli FB, Ramari C, Poncelet M, Severijns D, Kos D, Pau M, Kalron A, Meyns P, Feys P. Between-Day Reliability of the Gait Characteristics and Their Changes During the 6-Minute Walking Test in People With Multiple Sclerosis. Neurorehabil Neural Repair. 2024 Feb;38(2):75-86. doi: 10.1177/15459683231222412. Epub 2024 Jan 16.

  PMID: 38229519 BACKGROUND

• Nagels-Coune L, Benitez-Andonegui A, Reuter N, Luhrs M, Goebel R, De Weerd P, Riecke L, Sorger B. Brain-Based Binary Communication Using Spatiotemporal Features of fNIRS Responses. Front Hum Neurosci. 2020 Apr 15;14:113. doi: 10.3389/fnhum.2020.00113. eCollection 2020.

  PMID: 32351371 BACKGROUND

• Menant JC, Maidan I, Alcock L, Al-Yahya E, Cerasa A, Clark DJ, de Bruin ED, Fraser S, Gramigna V, Hamacher D, Herold F, Holtzer R, Izzetoglu M, Lim S, Pantall A, Pelicioni P, Peters S, Rosso AL, St George R, Stuart S, Vasta R, Vitorio R, Mirelman A. A consensus guide to using functional near-infrared spectroscopy in posture and gait research. Gait Posture. 2020 Oct;82:254-265. doi: 10.1016/j.gaitpost.2020.09.012. Epub 2020 Sep 18.

  PMID: 32987345 BACKGROUND

• Leone C, Severijns D, Dolezalova V, Baert I, Dalgas U, Romberg A, Bethoux F, Gebara B, Santoyo Medina C, Maamagi H, Rasova K, Maertens de Noordhout B, Knuts K, Skjerbaek A, Jensen E, Wagner JM, Feys P. Prevalence of Walking-Related Motor Fatigue in Persons With Multiple Sclerosis: Decline in Walking Distance Induced by the 6-Minute Walk Test. Neurorehabil Neural Repair. 2016 May;30(4):373-83. doi: 10.1177/1545968315597070. Epub 2015 Jul 27.

  PMID: 26216790 BACKGROUND

• Herold F, Wiegel P, Scholkmann F, Thiers A, Hamacher D, Schega L. Functional near-infrared spectroscopy in movement science: a systematic review on cortical activity in postural and walking tasks. Neurophotonics. 2017 Oct;4(4):041403. doi: 10.1117/1.NPh.4.4.041403. Epub 2017 Aug 1.

  PMID: 28924563 BACKGROUND

• Goldman MD, Chen S, Motl R, Pearsall R, Oh U, Brenton JN. Progression risk stratification with six-minute walk gait speed trajectory in multiple sclerosis. Front Neurol. 2023 Oct 4;14:1259413. doi: 10.3389/fneur.2023.1259413. eCollection 2023.

  PMID: 37859654 BACKGROUND

• Filli L, Sutter T, Easthope CS, Killeen T, Meyer C, Reuter K, Lorincz L, Bolliger M, Weller M, Curt A, Straumann D, Linnebank M, Zorner B. Profiling walking dysfunction in multiple sclerosis: characterisation, classification and progression over time. Sci Rep. 2018 Mar 21;8(1):4984. doi: 10.1038/s41598-018-22676-0.

  PMID: 29563533 BACKGROUND

• Baert I, Freeman J, Smedal T, Dalgas U, Romberg A, Kalron A, Conyers H, Elorriaga I, Gebara B, Gumse J, Heric A, Jensen E, Jones K, Knuts K, Maertens de Noordhout B, Martic A, Normann B, Eijnde BO, Rasova K, Santoyo Medina C, Truyens V, Wens I, Feys P. Responsiveness and clinically meaningful improvement, according to disability level, of five walking measures after rehabilitation in multiple sclerosis: a European multicenter study. Neurorehabil Neural Repair. 2014 Sep;28(7):621-31. doi: 10.1177/1545968314521010. Epub 2014 Feb 6.

  PMID: 24503204 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Fatigue

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: November 4, 2024
• Study Start: May 22, 2024
• Primary Completion: September 13, 2025
• Study Completion: December 1, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

BE (3)