Running Title: Walking to Music and in Silence on a Treadmill

Study Overview
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Brief Summary
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This work is embedded in the context of auditory-motor coupling, which entails the engagement of two systems; the interaction between the music (or repetitive auditory stimuli) and a walking individual (repetitive movements of footfall). In previous studies, the investigators have shown that synchronising steps to beats in music have shown to be feasible in persons with multiple sclerosis, showing increase of step frequency and reduced perceived fatigue[1, 2]. In this current work, The investigators expand previous findings with a pilot intervention study, to investigate if synchronisation is necessary to improve cognitive and motor functions. The proposed experiment includes 30 participants, randomised to three arms of a pilot intervention (10 participants per arm). With the intention of a further case-study analysis, the inestigators request to include 4 additional participants (2 PwMS with cognitive impairment, and 2 persons with cerebellar lesion) to only follow the intervention arm 1.

Official Title
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The Effect of a 4 Week Auditory-motor Coupling Intervention on Walking, Information Processing Speed and Fatigue in Persons With Multiple Sclerosis: Three Armed Pilot Intervention

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Walking with music with synchronisation
* Other: Walking with music without synchronisation
* Other: walking without music


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of MS if >1, no relapses >1 month, ability to walk for 12minutes, ability to walk independently on a treadmill walking speed between 0.8-1.2m/s. Exclusion Criteria: amusia, deafness, cognitive impairment hindering understanding of study instructions, pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Music with synchronising<br>walking to music that one can synchronise to | Other: Walking with music with synchronisation<br>* Walking with music than one can synch to<br>|
| Active Comparator: Music without synchronising<br>walking to music that one cannot synchronise to | Other: Walking with music without synchronisation<br>* Walking with music than one cannot synch to<br>|
| Sham Comparator: No music<br>walking without music. | Other: walking without music<br>* Walking without music<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12- item multiple sclerosis walking scale | The Multiple Sclerosis Walking Scale is a self-assessment scale which measures the impact of MS on walking. It consists of 12 questions concerning the limitations to walking due to MS during the past 2 weeks. Each item can be answered with 5 options, with 1 meaning no limitation and 5 extreme limitation. | Baseline | 
| 12- item multiple sclerosis walking scale | The Multiple Sclerosis Walking Scale is a self-assessment scale which measures the impact of MS on walking. It consists of 12 questions concerning the limitations to walking due to MS during the past 2 weeks. Each item can be answered with 5 options, with 1 meaning no limitation and 5 extreme limitation. | week 5 | 
| 6 minutes walking test to calculate the distance walking Index | impact of MS on walking | Baseline | 
| 6 minutes walking test to calculate the distance walking Index | impact of MS on walking | week 5 | 
| 12 minute walking with sensors | gait dynamics and pattern - detrended fluctuation analysis and spatio-temporal parameters | Baseline | 
| 12 minute walking with sensors | gait dynamics and pattern - detrended fluctuation analysis and spatio-temporal parameters | week 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paced auditory serial addition test and symbol digit modality test | to measure cognitive functioning and cognitive fatigability | Baseline | 
| Paced auditory serial addition test and symbol digit modality test | to measure cognitive functioning and cognitive fatigability | week 5 | 
| Motricity Index of dorsi flexors, knee extensors and hip flexors | Muscle weakness | Baseline | 
| Motricity Index of dorsi flexors, knee extensors and hip flexors | Muscle weakness | week 5 | 
| Modified Aschowrth scale Hamstrings, Tricepts Surae, Quadricepts | Spasticity | Baseline | 
| Modified Aschowrth scale Hamstrings, Tricepts Surae, Quadricepts | Spasticity | week 5 | 
| Scale for the assessment and rating of ataxia | Ataxia | Baseline | 
| Scale for the assessment and rating of ataxia | Ataxia | week 5 | 
| Dynamic gait index | Dynamic balance | Baseline | 
| Dynamic gait index | Dynamic balance | week 5 | 
| Time up and Go test | balance | Baseline | 
| Time up and Go test | balance | week 5 | 
| Modified fatigue impact scale | self-reported outcomes for fatigue | Baseline | 
| Modified fatigue impact scale | self-reported outcomes for fatigue | week 5 | 
| Barcelona music reward questionnaire | experience of music reward | Baseline | 
| Barcelona music reward questionnaire | experience of music reward | week 5 | 
| Hospital anxiety and depression questionnaire | anxiety and depression | Baseline | 
| Hospital anxiety and depression questionnaire | anxiety and depression | week 5 | 
| Activities-specific balance confidence scale | self-reported outcome for activity and balance | Baseline | 
| Activities-specific balance confidence scale | self-reported outcome for activity and balance | week 5 | 
| Stroke rehabilitation motivation scale | self-reported motivation questionnaire | Baseline | 
| Stroke rehabilitation motivation scale | self-reported motivation questionnaire | week 5 | 
| the Brunnel Music Rating Inventory-2 | self-reported music rating inventory | Baseline | 
| the Brunnel Music Rating Inventory-2 | self-reported music rating inventory | week 5 | 
| credibility and expectations questionnaire | self-reporting of credibility of the intervention. | week 5 | 
| Pre and Post training sessions, 2x a week, 20 minutes for 4 weeks | Before and after each training session Perceived cognitive and physical fatigue rated on a visual analogue scale Perceived motivation rated on a Likert scale | up to week 4 |