Multiple Sclerosis Clinical Trial
Official title:
Self-Management Program Based on Physical Exercises for People With Multiple Sclerosis With Mild Neurological Impairment: A Randomized Controlled Trial
Fatigue is the most chronic and disabling symptom in multiple sclerosis patients. Self-management physical exercise programs seem promising to allow patients to improve their fatigue and their deconditioning. However, the effectiveness of such programs has been poorly assessed until now. The objectives of the present study are to evaluate the relationships between fatigue and physical capacity among slightly affected MS patients, and to carry on a large trial to assess the effectiveness of a self-management exercise program in the same patients. Sixty-four patients will be included and will be asked, after an educational period, to perform at least three exercise sessions of more than 30 minutes each week, over a period of three months. Patients will be splitted in two groups : one group will perform endurance and resistance physical exercises, and the other one will perform relaxation exercises with the help of soothing music. A regular coaching will adapt the exercises and motivate the patients to continue the treatment. Assessors won't be informed of patients' treatment. Four evaluations will be done, and will notably assess muscle strength, endurance, fatigue and social participation.
Objectives: the aims of this project are two-fold:
- The first aim is to evaluate the relationships between fatigue and physical capacity,
among multiple sclerosis (MS) patients at the early stage of the disease and their
relations to plasmatic cytokines levels;
- The second aim is to assess the effectiveness of a self-management program of
physiotherapy, based on endurance and resistance physical exercises, in MS patients at
the early stage of the disease.
Rationale and scientific background:
Multiple sclerosis affects one person per thousand people in France and Belgium. Two
thousand patients are newly diagnosed in France each year. Fatigue is an early and very
disabling symptom of MS, that affects 50 to 80% of MS patients. Fatigue is described by
patients as the most chronic and the most disabling symptom and is associated with a decline
in motivation and a need for rest. Fatigue can occur spontaneously or can be induced by
physical or mental activity, acute infection, or ingestion of food. It can occur at any time
but usually worsens along the day.
Fatigue can have multiple origins in patients with MS: brain lesion load, cortical atrophy,
dysfunction of the hypothalamo-pituitary axis, depression or physical deconditioning.
Several approaches seem promising to improve fatigue: energy conservation programs, which
help patients in organizing their daily activities to avoid fatigue, cognitive behavioural
therapy, medications and physical exercise. Patients with MS show indeed a degradation of
their cardio-respiratory endurance. This degradation seems to occur early in the course of
MS, and to be already present in patients with mild neurological impairments. A
deconditioning is regularly found in patients complaining of fatigue. However, the
literature does not provide clear information about the relationship between physical
deconditioning and fatigue, at the very early stage of MS.
Exercise medicine is therefore a promising approach in the management of fatigue. Several
studies have shown an improvement of fatigue and gait ability after a program of physical
exercise. Dalgas (2008) and Sandoval (2013) have proposed recommendations on endurance and
resistance exercise in MS patients. Following their recommendations, endurance training
should be made through walking or cycling exercise, 2 to 3 times per week, at an intensity
corresponding to 60-80% of the predicted maximal heart rate. The recommended duration of
sessions is 10 to 40 minutes, depending on patients' motor impairments. Resistance training
should be preferentially supervised by therapists, at least for the first sessions. If the
training is self-managed or home-based, using the weight of the body or elastic bands seems
sufficient to bring an improvement in muscle strength. Three to four sets of exercises,
separated by 2-4 minutes rest periods, with an intensity of 8 to 15 repetitions at 70% of
the predicted maximum strength (RM), seem to be effective when carried out 2-3 times per
week. Each program should include 4 to 8 various exercises. Few studies have rated the
benefits of these programs in the long term and at the early stage of the disease. A
precocious exercise prescription could prevent deconditioning or its effects, including
fatigue.
Currently, a small number of patients benefits from physiotherapy treatments based on
physical exercise. On one hand, multidisciplinary rehabilitation programs (including
physiotherapy, occupational therapy, neuropsychology, physical exercise,...) are implemented
only when impairments are severe (e.g. immediately after a relapse), due to the strict
criteria of reimbursement established by social insurances. Therefore, patients who are only
slightly impaired cannot benefit from these programs. Moreover, the lack of rehabilitation
facilities allows only a limited number of patients to participate in multidisciplinary
programs. On the other hand, few rehabilitation centres organize face-to-face or group-based
physiotherapy programs specifically targeting physical exercise in patients with MS. Indeed,
these face-to-face programs remain mainly focused on neurodevelopmental theories (Bobath,…).
Finally, both multidisciplinary programs and specific exercise-based programs are mostly
implemented in hospitals and large centres of rehabilitation. However, such structures do
not seem necessary when the main objective is to do physical exercise, and can even be
stressful for those patients with mild impairments.
An alternative to these treatments may be self-management physical exercise programs,
supervised by physical medicine and rehabilitation teams. These programs only require a
limited cost for the patient and the society, and can be done in an ecological environment
(i.e. where the patient lives). These community-based rehabilitation programs could
therefore enable a better adhesion to treatment than hospital treatments. The effectiveness
of self-managed rehabilitation has poorly been assessed. Results of the literature are
conflicting, and the evidence is lacking. These authors pointed the need for further
randomised controlled trials.
The aim of our project is therefore to implement a physical exercise program in patients at
the early stage of MS, including resistance and cardio-respiratory endurance exercises. A
multicenter, single-blind, randomised controlled trial will be carried out to assess its
effectiveness. This project will also study the fitness and fatigue in patients whose
walking capacity is preserved.
It has also been noted that fatigue is related to the plasma levels of various cytokines
(e.g. Interleukin(IL)-6, IL-10, Interferon-gamma(IFNg), Tumor Necrosis Factor-alpha
(TNFa)...) and it has been suggested that physical exercise could reduce fatigue through an
effect on the transcription of the genes coding for these cytokines.
In the following sections, the term "self-management program" will refer to the whole
program, including education, exercises, and coaching of patients.
Research project:
This is a multicentre, single-blind, randomised controlled trial. All patients will
initially have a consultation with an investigator for the screening visit, two weeks before
inclusion. Inclusion and exclusion criteria will be checked, and a motivational interview of
the patient will be done. Randomisation will also be carried out during this visit, and will
be stratified to enable the equivalence of the Expanded Disability Status Scale (EDSS)
scores in both the experimental and the control groups. The randomization will be separate
for each center. The first evaluation will be performed the day of study inclusion (see
below), by another investigator. A same investigator will carry out all assessment of a same
patient. The second evaluation will take place two weeks later. Treatment will begin in the
week following this evaluation for patients of both groups. No detailed information will be
given to patients about the other group's treatment. They will only be informed that the aim
of the study is to compare two rehabilitation treatments, one based on physical exercises
and the other one based on relaxation.
Patients in the experimental group will participate in four two preliminary group-based
educational sessions of one hour. The first session, a group-based session, will aim to
explain the theoretical bases of physical exercise in MS disease (one hour). The next three
session, a face-to-face interviews will be devoted to the demonstration and initial practice
of the exercises that patients will have to perform during the self-management program
(three one hours).
Patients will have an individual appointment of thirty minutes immediately after the last
session, in order to define a program tailored to their individual goals. They will be asked
to do at least three physical exercise sessions per week, more than forty-five minutes each,
over a period of three months. The type of exercises and their intensity will be also
specified to the patient on this occasion. These exercises will be carried out through a
self-management program, and will then not be directly supervised by a therapist.
Patients in the control group will receive two four sessions (the first one in group and the
second explaining how to practice relaxation with the help of soothing music (four two
hours). They will then be invited to practice relaxation at home, for at least forty-five
minutes per day, at least three times a week, over a period of three months.
Two Three last evaluations will be conducted in patients: one within the week after the end
of the study, one six months after inclusion and one nine months after inclusion, in order
to assess the long-term effects of the treatment.
At the end of the study (nine months after the inclusion), all patients of the control group
will have the opportunity to benefit from a self-management program of exercises under
indirect supervision, comparable to the treatment received by the experimental group during
the study.
All patients will continue in parallel all other usual medical and paramedical treatments,
including physiotherapy, these treatments remaining unchanged during this project.
Protocol of exercises:
see below
Patients will have access to a virtual training book on the internet, in which they will be
asked to list all details about workouts within the hospital and at home (number, date,
duration, exercises conducted, intensity). If some patients do not have access to the
internet at home, a training logbook will be given at the inclusion, allowing them to list
the exercises details at each session.
The training will be monitored each week through the electronic training book, by a
therapist (physician or physical therapist), and recommendations on the self-management
training will be conveyed by this virtual logbook. A phone contact between the patient and
the therapist will be scheduled every two weeks. The patient will be encouraged to continue
these exercises on a regular basis. Recommendations will be tailored to patient's capacity
and to the exercises he will have been able to achieve the previous week. Every four weeks,
a group-based reminder session will take place in the referring hospital, one for the
experimental group and one for the control group, in order to check if there are some
adverse effects, if exercises are performed correctly, and if the patient remains motivated
for the continuation of support. The internet logbook of each patient will be reviewed on
this occasion by the therapist in order to adapt exercises to the patient's capabilities and
to the exercises carried out the previous weeks.
For patients who would have no internet at home, exercises will be followed and adapted each
week from a telephone contact between the patient and a therapist, and from a consultation
organised each two weeks to allow the therapist to examine the training book and to adapt
the exercises if necessary.
The relaxation sessions of the control group will be carried out with the help of soothing
music. Patients will receive a Compact Disc of soothing music at the inclusion. Patients
will also have an electronic training logbook that will be reviewed each week by a
therapist. They will have a phone contact with the therapist every two weeks, to discuss
about the treatment and adapt it if necessary. They will also have a reminder session every
four weeks.
Statistics:
Pearson and Spearman correlation coefficients will permit to study the relationships between
fatigue and physical capacity. The calculation of the intraclass correlation coefficient
will test the reproducibility of the two first evaluations. A two-factors analysis of
variance (ANOVA) will be carried out to investigate the effectiveness of the self-management
programs (Group X time). The Holm-Sidak test will be used as a post-hoc test.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment
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