Improving Mobility and Reducing Fatigue in People With Multiple Sclerosis by Electrical Stimulation Therapy

Study Overview
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Brief Summary
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The objective of the clinical trial is to quantify the capacity of a translatable protocol of electrical nerve stimulation (TENS) to improve walking performance and self-reported disabilities of persons with MS. The hypothesis is that activation of sensory nerve fibers with augmented TENS promotes recovery of sensorimotor function and improves the disability status of individuals with MS. The rationale for the proposed clinical trial is that the approach provides a low-cost therapeutic strategy for persons with MS to manage walking limitations and fatigue.

Detailed Description
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The study will involve a randomized, double-blind, controlled trial. Randomization will be accomplished by recruiting two individuals with a similar level of disability at a time and flipping a coin (two persons present) to determine the group assignment (A or B) of the person who contacted the investigators first. The participants and outcome assessors will be blinded to group assignment. Both groups will receive the treatment (real or sham) during the first 4 weeks (3 sessions/week)and then there will be an 8-week follow-up period. Participants will be evaluated at weeks 0, 4, 8, and 12.

Official Title
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Improving Mobility and Reducing Fatigue in People With Multiple Sclerosis by Electrical Stimulation Therapy

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Device: Transcutaneous electrical nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to read, write, and speak English to ensure safe participation in the project Clinical diagnosis of multiple sclerosis Mild-to-moderate level of disability On stable doses of symptom-treating medications No MS exacerbations within the last 30 day Healthy enough to complete the protocol as indicated by the absence of a medical diagnosis or condition that is considered to be an absolute or relative contraindication to participating in tests that involve electrical nerve stimulation (e.g., not implanted devices or internal metal) Able to arrange own transportation to Boulder campus Exclusion Criteria: Documented MS-related relapse within the last 30 days Medical diagnosis or condition that is considered to be a contraindication to participating in the intervention, such as major renal, pulmonary, hepatic, cardiac, gastrointestinal, HIV, cancer (other than basal cell cancer), other neurological disorders, or pregnancy. Vestibular disorder Musculoskeletal disorder History of seizure disorders >2 alcoholic drinks/day,or present history (last 6 months) of drug abuse Spasticity that requires the individual to change an activity more than once a week Skin disease or sensation problems in the legs or hands that influence some activities more than once a week Claustrophobia Metallic implants Inability to attend treatment sessions 3 days per week for 6 weeks

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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No

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 |
| --- | --- |
| Experimental: Augmented TENS<br>Transcutaneous electrical nerve stimulation applied to each leg separately while participants perform steady submaximal contractions. | Device: Transcutaneous electrical nerve stimulation<br>* Commercially available device will be used to apply weak electrical currents to arm and leg muscles in each of 18 treatment sessions.<br>* Other names: Sham transcutaneous electrical nerve stimulation;|
| Sham Comparator: Sham<br>Transient (10 s) application of transcutaneous electrical nerve stimulation applied to each leg separately while participants perform steady submaximal contractions . | Device: Transcutaneous electrical nerve stimulation<br>* Commercially available device will be used to apply weak electrical currents to arm and leg muscles in each of 18 treatment sessions.<br>* Other names: Sham transcutaneous electrical nerve stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Gait Speed | Time to walk 25 ft as quickly as possible | Change from baseline at weeks 4, 8, and 12. | 
| Change in Walking Endurance | Distance walked in 6 min when walking at a brisk pace | Change from baseline at weeks 4, 8, and 12 | 
| Change in Dynamic Balance | Score achieved on the four components of the 14-item Mini-Balance Evaluation Systems Test (Mini-BESTest). The maximum score for each subscale are: anticipatory = 6, reactive postural control = 6, sensory orientation = 6, dynamic gait = 10. The subscales are added to provide a total score with a maximum of 28. | Change from baseline at weeks 4, 8, and 12 | 
| Change in Patient Determined Disease Steps | A questionnaire with a self-assessment scale of disease status. The scores range from 0 = normal to 8 = bedridden. | Change from baseline at weeks 4, 8, and 12 | 
| Change in Modified Fatigue Impact Scale | A questionnaire that assesses the impact of fatigue experienced by persons with MS. Each of the 21 items is rated from 0 = Never to 5 = Almost always. The maximum total score = 105 | Change from baseline at weeks 4, 8, and 12. | 
| Change in MS Walking Scale-12 | A 12-item, patient-rated measure of how much MS compromises walking ability. Each item is rated from 1 = Not at all to 5 = extremely. The maximum total score = 60. | Change from baseline at weeks 4, 8, and 12. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Romberg Quotient | Ratio of the total sway area when standing with the eyes closed relative to that when the eyes are open. The test will be performed while standing on a firm surface and a foam surface. | Change from baseline at weeks 4, 8, and 12. | 
| Change Conditioned H-reflex Amplitude | Comparison of the percent reduction in the amplitude of the conditioned H-reflex amplitude in soleus while seated, standing with eyes open, and standing with eyes closed. | Change from baseline at weeks 4, 8, and 12. | 
| Change in Proprioception Tract | Change in MRI signal intensity in corticospinal tract | Change from baseline at weeks 4, 8, and 12. | 
| Change in Muscle Synergy Number | Non-negative matrix factorization will be used to identify the number of muscle synergies when subjects walk on a treadmill. | Change from baseline at weeks 4, 8, and 12 | 
| Change in Force Steadiness | The coefficient of variation for force when subjects perform steady, submaximal contractions. | Change from baseline at weeks 4, 8, and 12. | 
| Change in Muscle Synergy TIming | The timing of the muscle synergies when subjects walk on a treadmill. | Change from baseline at weeks 4, 8, and 12. | 
| Change in Discharge characteristics | The mean and coefficient of variation for the times between action potentials during steady isometric contractions. | Change from baseline at weeks 4, 8, and 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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walking, balance, fatigue