Clinical trial NCT02607020: Self-Management Program Based on Physical Exercises in People With Multiple Sclerosis
Official title: Self-Management Program Based on Physical Exercises for People With Multiple Sclerosis With Mild Neurological Impairment: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Hôpital Raymond Poincaré
name: CHU de Reims
First posted: 2015-11-17
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* A diagnosis of MS performed by a specialized neurologist (revised McDonald criteria, 2010), regardless of the form of the disease (relapsing-remitting, primary progressive, secondary progressive);
* An EDSS score less than or equal to 3.5, with a functional score less than or equal to 2 for the pyramidal and cerebellar functions;
* An age between 18 and 65 years.

Exclusion Criteria:

* An affection of one or both lower limbs limiting their ability to walk;
* Another illness contraindicating the practice of exercises (ACSM criteria, 2011);
* An episode of relapse within the 4 weeks prior to inclusion;
* Participation in a study targeting rehabilitation, within the 3 months prior to inclusion;
* Modification of drug treatment of MS (disease-modifying treatment and symptomatic treatment) in the 3 months prior to inclusion;
* Change in the physiotherapy prescription within the 3 months prior to inclusion.
* Pregnancy
* Participation in a regular exercise program at least 3 times a week for at least 30 minutes for more than 6 months.

Primary outcomes:
measure: Fatigue
timeFrame: 28 days
measure: Change in fatigue
timeFrame: Evaluation at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
Secondary outcomes:
measure: Safety (Number of patients with adverse events related to treatment).
timeFrame: Through study completion, an average of 9 months
measure: Change in MS-specific health related quality of life
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
measure: Change in MS-specific health related quality of life
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
measure: Change in walking capacity
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
measure: Change in plasmatic cytokines: IFNg
timeFrame: Baseline and immediately after the intervention
measure: Change in plasmatic cytokines: TNFa
timeFrame: Baseline and immediately after the intervention
measure: Adherence
timeFrame: Weekly through the intervention (during 3 months)
measure: Adherence
timeFrame: Weekly through the intervention (during 3 months)
measure: Amount of physical activity performed
timeFrame: From the first day after the completion of the treatment, every 3 months up to 6 months.
measure: Change in Cardiorespiratory fitness
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
measure: Change in Cardiorespiratory fitness
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
measure: Change in Lower limbs spasticity
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
measure: Change in objective walking endurance
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
measure: Change in static and dynamic balance
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
measure: Change in Neurological Disability
timeFrame: 2 evaluations at baseline, one immediately after the intervention program, one 3 months afterward and the last one 6 months after the end of the intervention
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques universitaires Saint-Luc
Study officials:
affiliation: UCL
name: Maxime VALET, MD
role: PRINCIPAL_INVESTIGATOR
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