Effects of the Cross-Training in Patients With Multiple Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether, in patients with multiple sclerosis presenting with marked asymmetry of strength, training the less-affected limb with a Cross-Training approach may induce a meaningful transfer of strength with neurophysiological, functional and clinical correlates, to the contralateral, more-impaired limb.

Detailed Description
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Muscle weakness is a major disability that is responsible for deeply reducing the overall quality of life (QoL) of patients with Multiple Sclerosis (MS). Research has shown that strength training (ST) has a significant positive effect on the performance of daily living activities in people with MS, resulting in an increased QoL. Several ST methods are currently employed for reducing strength impairment in MS but no one regimen has been portrayed as superior to others. When strength impairment is prominently lateralized to one limb, training is commonly addressed to the weaker side in order to balance the deficit. However, such ST may not always be applicable to a severely weakened limb that is too compromised to sustain it. For these selected patients we hypothesize that training the less affected limb with a Cross Training (CT) approach may overcome the problem, also avoiding patients' frustration and potential withdrawals from rehabilitation programs. Aim of this project is to investigate and compare in two groups of selected MS patients, with a marked asymmetry of strength, the effects induced on dynamometric, neurophysiological, functional and clinical outcomes by a CT of the less-impaired leg (CT group) compared to a ST of the more-impaired leg (ST group). In order to make comparisons with a population which is not exposed to the condition MS, a third group composed of healthy subjects will also be included in the study. The research plan will be articulated in 5 phases (recruitment, baseline assessment, 6 week-intervention phase, post-intervention assessment and follow up at 12 weeks).

Official Title
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Neurophysiological, Dynamometric, Functional and Clinical Assessment of the Cross-Training Effect in Patients With Multiple Sclerosis

Conditions
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Fatigue, Multiple Sclerosis, Weakness

Intervention / Treatment
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* Other: Cross-Training healthy subjects
* Other: Cross-Training multiple sclerosis
* Other: Standard-training multiple sclerosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-65 years Expanded Disability Status Scale (EDSS) ≤6 (Pyramidal functional system ≥3) Exclusion Criteria: Clinically relevant cognitive disorders; Disability caused by other diseases; Medication with corticosteroids within three months prior to enrolment; Medication with botulinum toxin within six months prior to enrolment; Clinically or radiologically documented exacerbation within six months prior to enrolment; Variations in disease-modifying drugs (DMD) within three months prior to enrolment; Severe ataxia and postural instability (assessed with Berg Balance Scale); Depression

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cross-Training healthy subjects<br>A cohort of healthy subjects (N=15) will undergo a phase of intervention consisting of cross-training of the stronger limb employing an isokinetic contraction regimen at maximal intensity. | Other: Cross-Training healthy subjects<br>* The phase of intervention will consist of a 6-week cross-training of the stronger limb employing an isokinetic contraction regimen at maximal intensity.<br>|
| Active Comparator: Standard-Training multiple sclerosis<br>A cohort of patients with multiple sclerosis (N=15), presenting with a marked asymmetry in limb strength, will undergo a standard-training of the more-impaired limb employing an isokinetic contraction regimen at maximal intensity. | Other: Standard-training multiple sclerosis<br>* The phase of intervention will consist of a 6-week standard strength training of the more-impaired limb employing an isokinetic contraction regimen performed at maximal intensity.<br>|
| Experimental: Cross-Training multiple sclerosis<br>A cohort of patients with multiple sclerosis (N=15), presenting with a marked asymmetry in limb strength, will undergo a cross-training of the less-impaired limb employing an isokinetic contraction regimen at maximal intensity. | Other: Cross-Training multiple sclerosis<br>* The phase of intervention will consist of a 6-week cross-training of the less-impaired limb employing an isokinetic contraction regimen at maximal intensity.<br>|
| No Intervention: Healthy Control<br>A cohort of healthy subjects (N=15) will undergo baseline assessment and a second evaluation after one month of no-intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscular strength | Strength changes in the weaker side compared to the contralateral, through isokinetic dynamometry. | Muscular strength will be assessed at baseline, within one week from the completion of the 6-week rehabilitation phase and at 12-week follow up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neural adaptations to Cross Training | Neural adaptations to CT occurring at cortical and/or spinal level, through transcranial magnetic stimulation (TMS) and peripheral electrophysiological recordings. | Neural adaptations will be assessed at baseline, within one week from the completion of the 6-week rehabilitation phase and at 12-week follow up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistance training/methods, contralateral strength training, ipsilateral strength training, Isokinetic contraction, Adaptation, Physiological/physiology, Electromyography/methods, Transcranial Magnetic Stimulation/methods, Evoked Potentials, Motor