How Does Strength Training and Balance Training Affect Gait Function and Fatigue in Patients With Multiple Sclerosis?

Study Overview
=================
Brief Summary
-----------------
Introduction: Multiple sclerosis (MS) is characterized by decreased strength and motor control, and compromised gait function. Reduced walking speed, balance, and fatigue are the cardinal symptoms. In rehabilitation, strength and balance training are commonly used. There is increasing scientific support of strength training for improving walking function. The evidence for balance training remains flawed. It is known that neurological damage in MS leads to increased cognitive processing in the planning of movements, which predisposes fatigue. Since fatigue is also associated with impaired balance, it can be hypothesized that motoric/balance training with an emphasis on cognitive load can affect gait and fatigue. Purpose: The aim of the study is to determine whether there is a differentiated effect between strength and balance training measured by motor function, strength, balance, and fatigue.

Detailed Description
-----------------
People with MS experience a wide variety of symptoms including impaired muscle strength and balance, fatigue, impaired cognition, depression and spasticity. Of these, impaired balance and severe fatigue are described as two of the most debilitating symptoms leading to limitations in activities such as upright posture and gait. Generally, pharmacological symptomatic treatment has not proven efficient in the treatment of balance problems, fatigue and walking impairments, with the exception that Fampridine has beneficial effects on gait performance in a subgroup of patients. Consequently, non-pharmacological interventions that effectively target these symptoms are warranted. In the last decade progressive resistance training (PRT) has proven to be one of the promising interventions in patients with MS showing a consistent and positive effect on muscle strength. However, the effect of PRT on functional outcomes are heterogeneous but with promising effects on daily activities such as walking and chair rise. The evidence for a beneficial effect of PRT on balance and postural control is divergent and yet inadequately investigated. Regarding fatigue, a recent Cochrane review reported that one could expect improvements in MS fatigue after exercise interventions, despite methodological flaws in the existing literature, but only few studies evaluating PRT were located. Another promising intervention is task specific training of motor function that is widely used by physiotherapists in neurorehabilitation. In this study protocol, motor function is limited to gait related functions with a particular focus put on balance and motor control, why the term Balance and Motor Control Training (BMCT) is applied. There is no universally accepted definition of human balance, but balance defined as the inherent ability of a person to maintain, achieve or restore a specific state of balance and not to fall, with reference to the motor and sensory systems and to the physical properties of the person, is applied in this study. Effects obtained from BMCT partly result from plastic changes in the nervous system. To induce such effects, repetition of a simple task only has limited efficiency in order to improve performance. Once a task has been learned to a certain level, further practice of the same task will not be accompanied by further induction of plasticity and little is therefore gained by continued practice of the task. To provide challenges that ensures continued learning, training exercises have to progress from simple movement trajectories to more complex movements, that also incorporates goal setting. Moreover, it has been shown that shaping and variation of tasks in combination with feedback on movement quality is of great importance for the learning outcome. The underlying concept for performing BMCT is, therefore, that improved motor control will optimize the movement strategy, which further leads to improved gait function. Regarding the effects of BMCT on fatigue, there are diverging results in the literature, but the literature on BMCT for patients with MS is generally of low quality with an inadequate description of interventions, why further studies are warranted. Interestingly, the principles of task specific training do fundamentally contrast the principles of PRT, that normally consist of monotonous movement patterns performed under heavy loading for a low number of repetitions. Consequently, studies comparing the effects of BMCT and PRT on gait function would add to the current literature as no studies doing so could be located. Such a comparison would help clarify whether potential effects are overlapping or differentiated and would therefore help guiding future rehabilitation interventions in persons with MS. The primary objective of this study is, therefore, to investigate and compare the effects of 10 weeks of PRT to BMCT on gait function, balance and fatigue in mobility limited persons with MS. It is hypothesized that PRT will be superior in improving maximal straight gait speed, whereas BMCT will have a greater impact on balance, fatigue, and more complex walking tasks that include elements of balance and coordination.

Official Title
-----------------
How Does Strength Training and Balance Training Affect Gait Function and Fatigue in Patients With Multiple Sclerosis?

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

Intervention / Treatment
-----------------
* Other: Balance training
* Other: Strength training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Diagnosed with multiple sclerosis. Expanded Disability Status Scale (EDSS) 2.0-6.5 and min. 2.0 in the functional system pyramidal function. Able to walk 100 m. Able to manage own transportation in relation to weekly training and tests. Six spot step test score > 8 sec. or Timed 25 foot walk > 5 sec. Exclusion criteria Co-morbidity in terms of dementia and alcohol abuse. Attack within the last eight weeks. Systematic intensive rehabilitation/training within the last three months. Adjustment of medication within two months before inclusion. This applies only for medication that affects gait performance and spasticity.

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

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Balance training<br>All sessions will start with a ten minute warm-up on either a treadmill or a cycle. The balance intervention will be conducted in stations/domains where balance is challenged in the five different functions: standing, walking, sit to stand, stepping, and a station that exercises vestibular and gaze control. Progression is achieved by adding exercises with increased balance requirements and by adding additional motoric and cognitive tasks to the exercises-dual-tasking. Intensity of the exercises is defined from an error-rate where an adequate level is 20-40 percent. The intervention is conducted according to a standardized framework that describes examples of exercises and progressions. | Other: Balance training<br> <br> |
| Experimental: Strength training<br>All sessions will start with a ten minute warm-up on a stationary bicycle, followed by strength training of primary muscle synergies in the lower extremities. All exercises will be performed on machines with patients sitting or lying, adequately supported. The exercises are leg press, knee extension, hip flexion, hamstring curl, and hip extension. Exercises are performed with a fast concentric phase and a slow eccentric phase.. Set, repetition, and load: Weeks 1 and 2, 3 sets of 10 repetitions at a load of 15 repetitions maximum (RM) Weeks 3 and 4, 3 sets of 12 repetitions at a load of 12RM Weeks 5 and 6, 4 sets of 12 repetitions at a load of 12RM Weeks 7 and 8, 4 sets of 10 repetitions at a load of 10RM Weeks 9 and 10, 4 sets of 8 repetitions at a load of 8RM. | Other: Strength training<br> <br> |
| No Intervention: Control group<br>On a waitlist. After ten weeks of waiting, and intervention that contains 50 percent strength training and 50 percent balance training begins. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gait speed measured by Six Spot Step Test | Six Spot Step Test | At baseline and again after 10 weeks | 
| Change in gait speed measured by Timed 25 Foot Walk | Timed 25 Foot Walk | At baseline and again after 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Fatigue: Fatigue is measured according to the Danish version of the modified fatigue impact scale. | At baseline and after 10 weeks | 
| Endurance | Six-minute walk | At baseline and after 10 weeks | 
| Self-evaluated gait function | MS walking scale | At baseline and after 10 weeks | 
| Temporospatial measures | Gait in fastest and self-selected speed is recorded by a Qualisys system for 3D analysis. Determinants are step and stride length, step width, time in swing and stance, gait speed, and hip and knee angles during gait. | At baseline and after 10 weeks | 
| Balance - static | (modified) Clinical test for sensory interaction and balance (CTSIB). The test is conducted on a force plate that measures movement of center of pressure (COP). Outcome is length of COP trajectory and elliptic area. | At baseline and after 10 weeks | 
| Balance - functional | Mini BESTest | At baseline and after 10 weeks | 
| Balance - confidence | The Activities-specific Balance Confidence Scale | At baseline and after 10 weeks | 
| Strength | Maximum voluntary isometric contraction in knee flexion and extension. Maximum voluntary isometric and isokinetic contraction in dorsal and plantar flexion. | At baseline and after 10 weeks |