Reducing Fatigue in People With Multiple Sclerosis by Treatment With TENS

Study Overview
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Brief Summary
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The objective of the randomized, sham-controlled trial will be to evaluate the effectiveness of treatment with transcutaneous electrical nerve stimulation (TENS) at reducing the level of fatigue experienced by people with MS.

Detailed Description
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We will compare the changes in self-reported levels of fatigue (symptom intensity) and measures of fatigability (work capacity) from before to after a 6-week intervention. Participants (18-65 yrs) will be randomly assigned to one of two groups: one group will receive an effective dose of TENS and the other group (control) will be given a sham dose of TENS. The treatment will be applied during 18 sessions (3x/week for 6 weeks) and delivered through electrodes placed on the skin overlying the dorsiflexor (tibialis anterior) and hip flexor (rectus femoris) muscles of both legs. Participants will be evaluated before (Week 0), during (Week 4), and after (Weeks 7 and 11) the 6-week intervention. Our long-term goal is to develop strategies that can reduce the impact of fatigue on the daily activities of persons with MS. The objective of the randomized, sham-controlled trial will be to evaluate the effectiveness of treatment with TENS at reducing the level of fatigue experienced by people with MS. Our central hypothesis is that treatment with TENS applied to selected leg muscles in people with MS will produce superior improvements in self-reported and measured levels of fatigue and fatigability compared with a sham dose of TENS.

Official Title
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Reducing Fatigue in People With Multiple Sclerosis by Treatment With Transcutaneous Electrical Nerve Stimulation

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: Men and women18-65 yrs Able to read, understand, and speak English to ensure safe participation in the project Clinical diagnosis of relapsing-remitting MS Self-reported difficulty with walking On stable doses of Ampyra, provigil, or other symptomatic-treating medications No relapse or systemic steroids within the last 30 days Able to arrange transportation to the Boulder campus Exclusion Criteria: Vision or hearing problems that have not been corrected Problems with sensations to temperature, pressure, or pain Any arm or leg problems that would influence the ability to hold a weight Surgery to the arms or legs that continues to bother the participant Metal implants Medical diagnosis or condition that is considered to be an absolute or relative contraindication to participating in exercise training, such as major renal, pulmonary, hepatic, cardiac, gastrointestinal, HIV, cancer (other than treated basal cell cancer), other neurological disorders, or pregnancy History of head injury or stroke Taking antidepressants, anticholinergics, stimulants, sedatives, cannabis, illicit drugs or medications to treat herpes or neurologic pain. Diagnosis of diabetes mellitus Poorly controlled hypertension History of seizure disorders ≥2 alcoholic drinks/day, or present history (last 6 months) of drug abuse Spasticity that requires the individual to change intended activities more often than once a week Skin diseases or sensation problems in the legs or hands that influences some activities more often than once a week Inability to attend exercise 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Effective dose<br>• The effective dose of TENS will be set at an intensity to elicit slight contractions in each target muscle, as we have done previously. It will be delivered as 5-Hz bursts (7 pulses at 100 Hz/burst) and applied during the light exercises. The applied current (<20 mA) will differ slightly for each of the four muscle groups and will be determined while the person is standing. The current will be set at the beginning of every treatment session for both groups of participants. | Device: Transcutaneous electrical nerve stimulation<br>* Electrical stimulation applied over selected leg muscle will activate sensory receptors that will transmit signals back into the central nervous system.<br>|
| Sham Comparator: Sham dose<br>• The current intensity for the sham dose will be set at sensory threshold, which will be less than that used for the effective dose. After beginning each exercise set, the current for the sham dose will decay to 0 mA within 30 s. In a preliminary study that included a sham dose of TENS, we found that only two of the experienced dancers in the sham group detected the gradual decline in TENS current from its initial value slightly above motor threshold when performing prescribed exercises. | Device: Transcutaneous electrical nerve stimulation<br>* Electrical stimulation applied over selected leg muscle will activate sensory receptors that will transmit signals back into the central nervous system.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Questionnaire scores - PROMIS Fatigue (MS) 8a | Changes at Weeks 4, 7, and 11 | 
| Walking limitations | Questionnaire scores - MS Walking Scale-12 | Changes at Weeks 4, 7, and 11 | 
| Walking endurance | 6-min walk test in meters | Changes at Weeks 4, 7, and 11 | 
| Mobility | Assessment of static and dynamic balance with Mobility Lab, APDM Inc | Changes at Weeks 4, 7, and 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life questionnaire | Questionnaire scores | Changes at Weeks 4, 7, and 11 | 
| Muscle strength | Maximal force in newtons applied by the dorsiflexors and hip flexors of each leg | Changes at Weeks 4, 7, and 11 |