Validity and Reliability of the 6-minute Walk Test Over a Distance of 6 Metres in People With Multiple Sclerosis
Conditions: Multiple Sclerosis
Sponsor: Haute Ecole de Santé Vaud

Protocol and statistical plan  
 
 
 
Validity and Reliability of the 6-minute Walk Test Over a 
Distance of 6 Metres in People With Multiple Sclerosis 
 
NCT number: 04228328 
 
10 January 2020 
 
 
 

Protocol and statistical plan  
Sponsor / 
Sponsor-
Investigator 
Pr Kenny Guex, Professeur HES associé, av. De Beaumont 21, 1011 Lausanne, t : +41 
21 316 80 46, kenny.guex@hesav.ch 
Study Title 
Validity and Reliability of the 6-minute Walk Test Over a Distance of 6 Metres in People 
With Multiple Sclerosis 
Short Title / 
Study ID 
VTM6M6m, CERVD-2019-01864 
Study 
Registration 
Clinicaltrial.gov : NCT04228328 
Swiss National Clinical Trial Portal : SNCTP000003657 
Study Category 
and Rationale 
Minimum risks (A category) 
The tests are current and usual tests in the normal care of people with multiple sclerosis. 
Participants only have to walk for 6 minutes and to turn around. This turn will be timed. 
Background and 
Rationale  
 
The 6-minute walk test is used by physiotherapists to monitor the walking endurance of 
patients with multiple sclerosis. The protocol for this test calls for a distance of 30 meters 
(6MWT30) to be walked. However, this distance is not always available in practices and at 
patients’ homes. The aim of this study is to validate a shorter version over a distance of 6 
meters (6MWT6) and to evaluate its intra-rater reliability and the reliability of the 
instrument. 
Risk / Benefit 
Assessment 
 
The risks are a temporary increase in fatigue and the risk of falling. 
The direct benefits go beyond the knowledge of the performance of the tests. The 
participants will have feedback on their walking abilities and will use these data for their 
phyisotherapeutic follow-up. Performing the tests will contribute to their training in walking 
and physical activity recommended in their situation. 
The indirect benefits are the satisfaction of being able to help research on the disease that 
impacts them directly. Indeed, if there is a good correlation and concordance between the 
6MWT6 and the 6MWT30, the use of the 6-minute test over 6 meters could be 
generalized. 
Objective(s) 
The main objective is to validate a different version of the 6MWT, the 6MWT6. 
The secondary objectives are to verify the reliability of this new version (of the instrument 
and of the rater) and to analyze the possible differences between the 6MWT6 and the 
6MWT30 (according to the speed at the half-turn and other parameters: age, gender, 
height, EDSS score, type of disease, time since last relapse) 
Endpoint(s) 
6-minute walk test over 6 meters: meters walked 
6-minute walk test over 30 meters: meters walked 
360 Degree Turn Test: time in seconds and number of steps 
Study Design 
Non-randomized validation study 
Statistical 
Considerations 
The primary objective is to validate a new version of the 6MWT over a distance of 6 m, so 
it is necessary to prove that there is an excellent correlation with the 6MWT30, the current 
reference. To do this, the data will be first presented, as means and standard deviations 
for normally distributed variables, and as medians and interquartile ranges for non-
normally distributed variables. The differences between the 6MWT6 and 6MWT30 will be 

plotted (absolute and relative values) and a test of comparison of means will be performed 
with Student's ttest.  
Than, a Pearson or Kendall coefficient (depending on the distribution of the data) will be 
used. Analysis of the degree of agreement according to the method described by Taffé 
(bias and precision plot) will supplement the Bland and Altmann plot (Taffé, 2018; Taffé et 
al., 2020).  
The secondary objective, reliability, will be assessed using the Intra Class Coefficient 
(ICC), according to the model: two-way mixed-effects as recommended by Koo (2016), as 
repeated measures cannot be considered as random sampling and absolute agreement, 
as agreement between repeated measures is sought (Koo & Li, 2016). The 6MWT6 data 
at Day1 will be compared to the same data at Day2 to assess intrarater reliability. These 
data will be compared to the post hoc count based on the video performed at Day1 and 
Day2 for instrument reliability.  
For the last objective, analysis of explanatory factors for the differences between 6MWT6 
and 6MWT30, correlation analyses will be performed between the continuous variable of 
these differences and the 360DTT. Multiple linear regressions will then be performed 
between this dependent variable "6MWT30 - 6MWT6" and the continuous and categorical 
variables: 360 DTT (time), age, gender, height, time since last relapse, type of MS, and 
assistive device. All analyses will be performed using STATA software, v.15.1. (StataCorp 
LLC, College Station, TX, USA). 
Inclusion- / 
Exclusion 
Criteria 
The project focuses on the population of walking patients with MS.  
Inclusion: adults, confirmed diagnosis of MS, Expanded Disability Status Scale (EDSS) 
score 3 to 6.5, or be able to walk 30 metres with or without aids, good understanding of 
French, have already completed a 6-minute walking test, be able to give consent by 
signature. 
Exclusion: Lung disease, heart disease, co-morbidity preventing 6minWT, relapse in the 
last 3 months, chronic fatigue ≥ at 8 (Visual Analog Score-Fatigue). 
Number of 
Participants 
with Rationale 
21 participants will be needed to obtain a good correlation coefficient, which is the 
objective of the validation of the new version of the 6MWT. The alpha was set at 0.01, the 
power at 0.9 for a correlation of 0.8 
Study 
Intervention 
Test under study: People have to walk for 6 minutes without stopping when possible. 
Control 
Intervention 
No control intervention. 
Study 
procedures 
Eligible patients will be recruited by their treating physiotherapist or through the 
presentation of the project to the regional groups of the Swiss MS Society. The patients 
will be interns at the Institution or will come to the Institution of Lavigny for 2 times 1 hour 
and 20 minutes of testing at one week intervals. On the first day (Day1), they will perform 
the 6MWT6, followed by a 15-45 minutes lying down break, then they will perform the 360 
Degree Turn Test. On the second day (Day2), they will perform the 6MWT30 and then the 
6MWT6, interspersed with a 15-45 minutes break. 
Study Duration 
and Schedule 
March to November 2020 
Investigator(s) 
Sylvie Ferchichi-Barbey, physical therapist Bsc, student in Master of Sciences.  
21 years of experience with multiple sclerosis patients 
Study Center(s) 
Insitution de Lavigny, Rte du Vignoble 60 - 1175 Lavigny 
Tél. 021 821 46 17  
Switzerland 

Ethical 
consideration 
1. 
The results of this study would be generalized to the population of MS walkers 
with an EDSS between 3 and 6.5. They will allow the use of a valuable tool, the 6MWT6, 
in previously impossible contexts, i.e. in the practices and at patients' homes. Participants 
will benefit directly from feedback on their abilities, be able to compare these results to 
previous results and use this data for their phyisotherapeutic follow-up. Performing the 
tests will contribute to their training in walking and in the physical activity recommended 
for their situation. The indirect benefits are the satisfaction of being able to help research 
on the disease that impacts them directly. The main risk is a temporary increase in fatigue. 
2. 
The proposed methodology is ethical because, in order to evaluate the reliability 
and validity of a test, while excluding the fatigue bias, it would be necessary to call the 
patient 3 times at a few days interval. In this context, it was attempted to do it in 2 days 
rather than 3 and the impact of fatigue was minimized through the systematization of the 
breaks in lying position with adjustable duration according to the patient's condition. 
GCP 
Statement 
This study will be conducted in compliance with the protocol, the current version of the 
Declaration of Helsinki, the ICH-GCP, the HRA as well as other locally relevant legal and 
regulatory requirements. A clinical trial covered by ClinO Chapter 4 may be conducted in 
accordance with other rules than ICH-GCP guidelines, provided that such rules are 
recognised in the specialty in question and the protection of participants and data quality 
and security are guaranteed (ClinO Art. 5, Abs 2). If the clinical trial is not conducted 
according to ICH-GCP guidelines, the paragraph above must be adapted accordingly.