Underlying Causes and Related Factors, and Rehabilitation Approaches

Study Overview
=================
Brief Summary
-----------------
This study will be a cross-sectional observational study, followed by a pilot intervention. The aim of the study is to examine the underlying causes of walking-related performance fatigability, together with other related and influencing factors, to make up a clinical profile of patients with MS showing walking-related performance fatigability. In the second part of the study a pilot intervention will be executed to see if the investigators can improve the clinical status of the MS patients with walking-related performance fatigability.

Official Title
-----------------
Walking-related Performance Fatigabitity in People With Multiple Sclerosis: Clinical Profile o

Conditions
-----------------
Multiple Sclerosis

Intervention / Treatment
-----------------
* Other: Training intervention + Dance intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 70 years. MS diagnosis according to McDonald Criteria. Capable of walking 6 minutes (independent or with unilateral support) without stopping. Exclusion Criteria: Exacerbation or relapse within last 3 months before study Other medical condition interfering with walking ability (e.g. cardiac or respiratory diseases, arthritis and fibromyalgia, stroke, Parkinson).

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Persons with MS, dance group<br> | Other: Training intervention + Dance intervention<br>* Training intervention + Dance intervention<br>|
| Active Comparator: Persons with MS, art group<br> | Other: Training intervention + Dance intervention<br>* Training intervention + Dance intervention<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Coordination test | Participant is seated with legs strapped in to the mounts and moves legs to the beat of a metronome to assess central motor control. | Day 1 | 
| TST (Triple Stimulation Technique) | Technique in which nerves are stimulated to check guidance in the central nervous system | day 3 | 
| TMS (Transcranial Magnetic Stimulation) | Technique in which nerves are stimulated to check guidance in the central nervous system | Day 3 | 
| the Voluntary Drive test | The participant is seated in a Biodex. While performing a leg extension the Quadriceps muscle is stimulated to check the guidance of electrical signals to the muscles. | Day 1 | 
| the Fatigability Index Legs | Participant is seated in a Biodex and a protocol is performed to establish the muscle strength and muscle endurance of the legs. | Day 1 | 
| Analysis of a Muscle Biopsy | A small piece of muscle tissue of the weakest leg will be biopsied and analyzed in the lab. | Day 3 | 
| the Digit Span | Cognitive test where numbers must be recalled in a certain order to evaluate short term memory | Baseline | 
| the Digit Span | Cognitive test where numbers must be recalled in a certain order to evaluate short term memory | Week 11 | 
| the Stroop test | Cognitive test to evaluate attention and simultaneous processing of multiple stimuli. | Baseline | 
| the Stroop test | Cognitive test to evaluate attention and simultaneous processing of multiple stimuli. | week 11 | 
| the Paced Auditory Serial Addition Test (PASAT) | This is a cognitive test where the participant will try to retain certain numbers they hear and do math. Correct answer last 1/3 vs first 1/3 | Baseline | 
| the Paced Auditory Serial Addition Test (PASAT) | This is a cognitive test where the participant will try to retain certain numbers they hear and do math. Correct answer last 1/3 vs first 1/3 | Week 11 | 
| the Symbol Digit Modality Test (SDMT) (Cognitive fatigability) | his is a cognitive performance test, substantiated with focus, speed, and visual scanning. Correct answers last 30 seconds vs first 30 seconds | Baseline | 
| the Symbol Digit Modality Test (SDMT) (Cognitive fatigability) | his is a cognitive performance test, substantiated with focus, speed, and visual scanning. Correct answers last 30 seconds vs first 30 seconds | week 11 | 
| Motor function test (lower limb muscle strength) | This is a motor test to assess the functional lower limb muscle strength. The participant is asked to stand from a seated position and sit down again as fast as possible for five times in a row. | Baseline | 
| Motor function test (lower limb muscle strength) | This is a motor test to assess the functional lower limb muscle strength. The participant is asked to stand from a seated position and sit down again as fast as possible for five times in a row. | week 11 | 
| 25 Foot Walk (T25FW) test | his is a motor test at which the participant is instructed to walk 25 ft (=7,62 meter) as fast and safely as possible. This is a quantitative performance test to assess mobility and leg function. | Baseline | 
| 25 Foot Walk (T25FW) test | his is a motor test at which the participant is instructed to walk 25 ft (=7,62 meter) as fast and safely as possible. This is a quantitative performance test to assess mobility and leg function. | week 11 | 
| Nine Hole Peg Test (NHPT) | This is a motor test to assess the participant's manual skills. This test records the time the participant needs to place 9 pins in the pegboard and remove them again. | Baseline | 
| Nine Hole Peg Test (NHPT) | This is a motor test to assess the participant's manual skills. This test records the time the participant needs to place 9 pins in the pegboard and remove them again. | week 11 | 
| Fatigability Index Hand | Grip strength will be evaluated through a Jamar dynamometer. | Baseline | 
| Fatigability Index Hand | Grip strength will be evaluated through a Jamar dynamometer. | week 11 | 
| Activity tracker | A sensor will be placed around the foot and worn by the participant for 5 days and nights to evaluate physical activity and quality of sleep. | Up to 5 days | 
| Glycocheck | A small camera will be placed under the tongue of the participant and blood vessels will be filmed to determine the quality of the blood vessels and immunity. | Baseline | 
| Six minute walking test | Participant have to walk as far as they can for 6 minutes. Total distance walked and fatigability by comparing first and last minute distance will be calculated. | once during the observational study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue severity scale (FSS) | A self-report scale of nine items about fatigue, its severity and how it affects certain activities. Answers are scored on a seven point scale where 1 = strongly disagree and 7 = strongly agree. This means the minimum score possible is nine and the highest is 63. The higher the score, the more severe the fatigue is and the more it affects the person's activities. It is simple to understand and takes an average of eight minutes to answer | baseline | 
| Fatigue severity scale (FSS) | A self-report scale of nine items about fatigue, its severity and how it affects certain activities. Answers are scored on a seven point scale where 1 = strongly disagree and 7 = strongly agree. This means the minimum score possible is nine and the highest is 63. The higher the score, the more severe the fatigue is and the more it affects the person's activities. It is simple to understand and takes an average of eight minutes to answer | week 11 | 
| Modified Fatigue Impact Scale (MFIS) | This is a short questionnaire to evaluate to impact of general fatigue. This questionnaire measures the effects of fatigue on three levels: physical, cognitive and psychosocial. The MFIS is a 21-item questionaire, scale 0 (never)-4 (always), scale range 0-40 | baseline | 
| Modified Fatigue Impact Scale (MFIS) | This is a short questionnaire to evaluate to impact of general fatigue. This questionnaire measures the effects of fatigue on three levels: physical, cognitive and psychosocial.The MFIS is a 21-item questionaire, scale 0 (never)-4 (always), scale range 0-40 | week 11 | 
| Fatigue Scale of Motor and Cognitive Functions (FSMC) | This is a short questionnaire to cognitive and motor fatigue in people with MS. The FSMC is an assessment of MS-related cognitive and motor fatigue. A Likert-type 5-point scale (ranging from 'does not apply at all' to 'applies completely') produces a score between 1 and 5 for each scored question. Thus minimum value is 20 (no fatigue at all) and maximum value is 100 (severest grade of fatigue). Two subscales (mental and physical fatigue) can be made. Items included in the subscale mental are 1-4-7-8-11-13-15-17-18-20 and items included in the subscale physical are 2-3-5-6-9-10-12-14-16-19. | baseline | 
| Fatigue Scale of Motor and Cognitive Functions (FSMC) | This is a short questionnaire to cognitive and motor fatigue in people with MS. The FSMC is an assessment of MS-related cognitive and motor fatigue. A Likert-type 5-point scale (ranging from 'does not apply at all' to 'applies completely') produces a score between 1 and 5 for each scored question. Thus minimum value is 20 (no fatigue at all) and maximum value is 100 (severest grade of fatigue). Two subscales (mental and physical fatigue) can be made. Items included in the subscale mental are 1-4-7-8-11-13-15-17-18-20 and items included in the subscale physical are 2-3-5-6-9-10-12-14-16-19. | week 11 | 
| Hospital Anxiety and Depression Scale (HADS) | This is a short questionnaire that evaluates symptoms of anxiety and depression in daily life. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.. | baseline | 
| Hospital Anxiety and Depression Scale (HADS) | This is a short questionnaire that evaluates symptoms of anxiety and depression in daily life. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression. | Week 11 | 
| The Sleep Condition Indicator (SCI) | This is a short questionnaire to evaluate sleeping pattern and potential sleeping disorders. The Sleep Condition Indicator (SCI) is an eight-item rating scale (4-0) that was developed to screen for insomnia disorder based on DSM-5 criteria. | baseline | 
| The Sleep Condition Indicator (SCI) | This is a short questionnaire to evaluate sleeping pattern and potential sleeping disorders. The Sleep Condition Indicator (SCI) is an eight-item rating scale (4-0) that was developed to screen for insomnia disorder based on DSM-5 criteria. | week 11 | 
| Social Role Participation Questionnaire (SRPQ) | This is a short questionnaire to evaluate social participation. scale 1 (not important) - 5(very important) | baseline | 
| Social Role Participation Questionnaire (SRPQ) | This is a short questionnaire to evaluate social participation. scale 1 (not important) - 5 (very important) | week 11 | 
| pre-interventionMSWS-12 score | short questionnaire to map out walking difficulties in daily living. 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. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores. | baseline | 
| post-interventionMSWS-12 score | short questionnaire to map out walking difficulties in daily living. 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. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores. | baseline | 
| pre-interventionMSWS-12 score | short questionnaire to map out walking difficulties in daily living. 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. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores. | week 11 | 
| post-interventionMSWS-12 score | short questionnaire to map out walking difficulties in daily living. 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. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores. | week 11 | 
| Multiple Sclerosis Impact Scale (MSIS-29) | This is a short self-report questionnaire used to assess the day-to-day life in the past two weeks. This questionnaire has a physical and psychological scale. The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 not at all to 5extremely. Each of the two scales are scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates greater impact of disease on daily function (worse health). The physical impact score is computed by summing items number 1-20 inclusive. This score can then be transformed to a score on a scale of 0 -100 | Baseline | 
| Multiple Sclerosis Impact Scale (MSIS-29) | This is a short self-report questionnaire used to assess the day-to-day life in the past two weeks. This questionnaire has a physical and psychological scale. The MSIS-29 is a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 not at all to 5extremely. Each of the two scales are scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates greater impact of disease on daily function (worse health). The physical impact score is computed by summing items number 1-20 inclusive. This score can then be transformed to a score on a scale of 0 -100 | week 11 | 
| Short Form Health survey (SF-36) | questionnaire to measure health status. The Optum® SF-36v2® Health Survey asks 36 questions to measure functional health and well-being from the patient's point of view. It is a practical, reliable and valid measure of physical and mental health that can be completed in five to ten minutes. | Baseline | 
| Short Form Health survey (SF-36) | questionnaire to measure health status. The Optum® SF-36v2® Health Survey asks 36 questions to measure functional health and well-being from the patient's point of view. It is a practical, reliable and valid measure of physical and mental health that can be completed in five to ten minutes. | week 11 |