TENS for Multiple Sclerosis Fatigue

Overseen By Roger Enoka, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Boulder

Must be taking: Ampyra, Provigil

Must not be taking: Antidepressants, Anticholinergics, Stimulants, Sedatives

Disqualifiers: Diabetes, Hypertension, Seizure disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 20

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if transcutaneous electrical nerve stimulation (TENS) can reduce fatigue in people with multiple sclerosis (MS). Participants will receive either an active TENS treatment or a sham version for comparison. The trial seeks individuals with relapsing-remitting MS who have difficulty walking and can attend sessions in Boulder, CO. As an unphased trial, this study provides participants the chance to contribute to innovative research that could enhance MS fatigue management.

Will I have to stop taking my current medications?

The trial requires that participants are on stable doses of medications like Ampyra or Provigil, but you cannot participate if you are taking antidepressants, anticholinergics, stimulants, sedatives, cannabis, illicit drugs, or medications for herpes or neurologic pain.

What prior data suggests that TENS is safe for reducing fatigue in people with MS?

Research has shown that TENS (Transcutaneous Electrical Nerve Stimulation) is generally safe and well-tolerated. Studies have used TENS to reduce pain and fatigue in conditions like fibromyalgia and multiple sclerosis (MS). One study found that TENS significantly lessened pain and fatigue in women with fibromyalgia.

For people with MS, TENS may help with walking difficulties and reduce fatigue. The treatment involves placing a small electrical device on the skin, which might cause slight muscle twitches. These are usually manageable, with only mild discomfort reported by some.

While specific side effects aren't detailed in the sources, the general use of TENS in various conditions suggests it is quite safe. For those considering joining a trial, this information can reassure about the safety of this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Transcutaneous Electrical Nerve Stimulation (TENS) for multiple sclerosis (MS) fatigue because it offers a non-invasive, drug-free alternative to managing symptoms. Unlike traditional treatments that often involve medications like amantadine or modafinil, TENS works by delivering electrical impulses to nerves, which might help reduce fatigue by enhancing muscle activation during light exercise. This method is particularly promising since it allows for muscle-specific targeting without the side effects commonly associated with pharmacological options.

What evidence suggests that TENS is effective for reducing fatigue in MS?

Studies have shown that Transcutaneous Electrical Nerve Stimulation (TENS) can reduce tiredness in people with multiple sclerosis (MS). Research indicates that applying TENS to specific leg muscles improves movement and reduces fatigue. Other studies have found that TENS lessens pain and enhances daily activity performance. In this trial, participants will receive either an effective TENS dose, set to elicit slight muscle contractions, or a sham dose, set at a sensory threshold. This suggests that TENS might be a promising way to help people with MS feel less tired and more active. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with relapsing-remitting Multiple Sclerosis who experience walking difficulties. They must be on stable medication, have no recent MS relapses or steroid use, and can travel to Boulder campus. Excluded are those with uncorrected vision/hearing issues, certain physical conditions, metal implants, major diseases like HIV/cancer, history of head injury/stroke/seizures/drug abuse/alcoholism.

Inclusion Criteria

I have trouble walking.

I haven't had a relapse or taken steroids in the last 30 days.

I can get to the Boulder campus for my appointments.

Exclusion Criteria

I have had a head injury or stroke in the past.

Metal implants

≥2 alcoholic drinks/day, or present history (last 6 months) of drug abuse

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TENS treatment or sham dose for 6 weeks, 3 times per week

6 weeks

18 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• TENS

Trial Overview The study tests if TENS (Transcutaneous electrical nerve stimulation) can reduce fatigue in people with MS. Participants will be randomly assigned to receive either the real TENS treatment or a sham (fake) version to compare effectiveness.

How Is the Trial Designed?

Group I: Effective dose Experimental Treatment 1 Intervention

• 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.

Group II: Sham dose Placebo Group 1 Intervention

• 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.

Who Is Running the Clinical Trial?

University of Colorado, Boulder

Lead Sponsor

Trials

128

Recruited

29,600+

Published Research Related to This Trial

In a study involving 39 fibromyalgia patients, using two active TENS devices simultaneously resulted in greater pain relief and reduced fatigue compared to using one device or a placebo, with significant improvements in pain scores and quality of sleep.

Both the single TENS group and the dual TENS group reported a reduction in the use of analgesic tablets, indicating that TENS therapy can effectively manage pain without the need for additional medication, and no side effects were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the use of two simultaneously TENS devices for fibromyalgia pain. Lauretti, GR., Chubaci, EF., Mattos, AL.[2021]

Amantadine is the only medication with proven effectiveness for treating fatigue in multiple sclerosis, supported by randomized, double-blind, controlled trials.

While serotonin re-uptake inhibitors are used to address fatigue due to their link with depression, and aminopyridines may help with exercise-related fatigue, the overall mechanisms of fatigue in multiple sclerosis remain poorly understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic indications for managing symptoms: fatigue]. Waubant, E.[2022]

Transcutaneous electrical nerve stimulation (TENS) significantly reduces pain and fatigue in women with fibromyalgia, with a number needed to treat ranging from 3.3 to 5.3, indicating it is an effective intervention.

Initial response to TENS treatment, along with factors like marital status and sleep impairment, can predict long-term improvements in pain and fatigue, making TENS a clinically useful option for managing fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction in movement-evoked pain and fatigue during initial 30-minute transcutaneous electrical nerve stimulation treatment predicts transcutaneous electrical nerve stimulation responders in women with fibromyalgia. Vance, CGT., Zimmerman, MB., Dailey, DL., et al.[2023]

Amantadine has been shown to improve fatigue in multiple sclerosis patients, based on a systematic review of 11 clinical trials, indicating its potential as a treatment option.

The drug is generally well-tolerated with mild side effects, but further research with larger studies and standardized fatigue measurements is needed to confirm its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of amantadine for the treatment of fatigue in multiple sclerosis: a systematic review and meta-analysis. Perez, DQ., Espiritu, AI., Jamora, RDG.[2021]

Electrical stimulation therapy (EST) has been found to be effective in reducing pain in multiple sclerosis (MS) patients, with a significant mean difference of -1.75 on the visual analog scale based on data from 267 participants across 8 trials.

The study indicates that medium-term EST treatment provides the greatest pain relief compared to short-term and long-term treatments, and importantly, no adverse events related to EST were reported, suggesting it is a safe intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation therapy for pain and related symptoms in multiple sclerosis: A systematic review and meta-analysis. Wu, F., Li, X., Liang, J., et al.[2023]

The COMBO-MS trial is designed to compare the effectiveness of cognitive behavioral therapy (CBT), modafinil, and their combination in reducing fatigue in patients with multiple sclerosis (MS) over a 12-week period, involving random assignment of participants with significant fatigue.

The study aims to determine if combination therapy is more effective than either treatment alone and to explore how factors like depression, sleep disorders, and disease severity may influence treatment outcomes, which could lead to better management strategies for MS-related fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized pragmatic trial of telephone-delivered cognitive behavioral-therapy, modafinil, and combination therapy of both for fatigue in multiple sclerosis: The design of the "COMBO-MS" trial. Kratz, AL., Alschuler, KN., Ehde, DM., et al.[2020]

In a study involving 59 people with multiple sclerosis, both nortriptyline and self-applied TENS were found to be equally effective in reducing pain and sensory complaints in the upper extremities over an 8-week treatment period.

While both treatments significantly decreased pain intensity, TENS may be preferable due to a more favorable side-effect profile compared to nortriptyline, which is important for patient safety and comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensory complaints of the upper extremities in multiple sclerosis: relative efficacy of nortriptyline and transcutaneous electrical nerve stimulation. Chitsaz, A., Janghorbani, M., Shaygannejad, V., et al.[2013]

In a study of three multiple sclerosis (MS) patients with severe fatigue, treatment with picotesla flux electromagnetic fields (EMFs) led to significant improvements in their fatigue levels, even allowing for recovery after physical activity.

The findings suggest that EMFs may help replenish neurotransmitter stores in damaged neurons, potentially improving impulse conduction in the brain and alleviating fatigue symptoms in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with weak electromagnetic fields improves fatigue associated with multiple sclerosis. Sandyk, R.[2019]

Transcutaneous electrical nerve stimulation (TENS) has been shown to be a safe and effective non-drug treatment for managing central pain in people with multiple sclerosis, with a medium-sized effect size (Hedges' g=0.35) based on a meta-analysis of four studies.

The study found that the frequency of TENS used did not significantly affect the results, indicating that TENS can be a reliable option for pain management regardless of the specific type of stimulation applied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of efficacy of TENS for management of central pain in people with multiple sclerosis. Sawant, A., Dadurka, K., Overend, T., et al.[2018]

Transcranial direct current stimulation (tDCS) has shown promise in reducing fatigue in individuals with multiple sclerosis, particularly in a randomized trial where significant fatigue reduction was observed in the active treatment group compared to sham (p=0.02).

The study involved two phases: the first with 15 participants receiving open-label tDCS showing modest fatigue reduction, and the second with 27 participants in a randomized trial demonstrating a more substantial effect, suggesting that tDCS could be a viable treatment option for managing MS-related fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remotely supervised transcranial direct current stimulation for the treatment of fatigue in multiple sclerosis: Results from a randomized, sham-controlled trial. Charvet, LE., Dobbs, B., Shaw, MT., et al.[2019]

In a study involving 25 multiple sclerosis patients, pulsed magnetic field therapy (PMFT) showed a statistically significant immediate reduction in fatigue after a single session, with an 18% decrease compared to 11% in the control group.

However, over the course of the rehabilitation program, PMFT did not lead to a significant long-term reduction in fatigue compared to sham therapy, suggesting that its benefits may be limited and overshadowed by a strong placebo effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of pulsed magnetic field therapy on the level of fatigue in patients with multiple sclerosis--a randomized controlled trial. Mostert, S., Kesselring, J.[2017]

Fatigue affects up to 90% of multiple sclerosis (MS) patients and significantly impacts their quality of life, highlighting the need for effective treatments.

Transcranial direct current stimulation (tDCS) has shown promise as a safe and effective alternative therapy for MS-related fatigue, with protocols typically involving 5 consecutive daily sessions that have yielded beneficial effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation: A glimmer of hope for multiple sclerosis fatigue? Ayache, SS., Chalah, MA.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05500963

Reducing Fatigue in People With Multiple Sclerosis by ... 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 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2211034823000457

The effect of Transcutaneous Electrical Nerve Stimulation ... In this study, it was found that interference current and TENS applications decrease pain and increase functional capacity.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03684369

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

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9611192/

Using TENS for Pain Control: Update on the State of the ... TENS was more effective than the control group in improving functional disability only in patients with follow-up of < 6 weeks. TENS was similar to the control ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2211034823006156

Electrical stimulation therapy for pain and related ... MS patients were able to maximize the effect of electrical stimulation therapy (2 weeks-4 weeks) on pain symptoms from the medium-term EST treatment. However, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7188591/

Transcutaneous Electrical Nerve Stimulation Reduces ... Active transcutaneous electrical nerve stimulation (TENS) use significantly decreased pain and fatigue in women with fibromyalgia during activity and at rest

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06432686

Neurophysiological Effects of Transcutaneous Electrical ... Transcutaneous Electrical Nerve Stimulation (TENS) is a treatment that could potentially reduce walking problems and fatigue in persons with Multiple Sclerosis.