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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the treatment TENS for reducing fatigue in multiple sclerosis?

Research shows that TENS can reduce pain and fatigue in people with fibromyalgia, suggesting it might also help with similar symptoms in multiple sclerosis. Additionally, TENS has been evaluated for treating sensory complaints in MS, indicating potential benefits for managing fatigue. ^{1 2 3 4 5}

Is TENS safe for use in humans?

TENS (transcutaneous electrical nerve stimulation) is generally considered safe for humans, with minor side effects reported in some cases. In studies involving fibromyalgia, the number of people experiencing minor adverse effects from TENS was low, suggesting it is a safe option for managing pain and fatigue. ^{1 6 7 8 9}

How does TENS treatment differ from other treatments for multiple sclerosis fatigue?

TENS (Transcutaneous Electrical Nerve Stimulation) is unique because it is a non-drug therapy that uses electrical currents to relieve symptoms, unlike many treatments that rely on medications with potential side effects. It is applied externally and can be used at home, offering a convenient and side-effect-free option for managing fatigue in multiple sclerosis. ^{4 9 10 11 12}

Eligibility Criteria

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 am between 18 and 65 years old.

Able to read, understand, and speak English to ensure safe participation in the project

I have trouble walking.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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 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]

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) 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]

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]

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]

References

1. United States 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. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Electrical stimulation therapy for pain and related symptoms in multiple sclerosis: A systematic review and meta-analysis. [2023]

3. United States 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. [2020]

4. England 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. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Sensory complaints of the upper extremities in multiple sclerosis: relative efficacy of nortriptyline and transcutaneous electrical nerve stimulation. [2013]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of the use of two simultaneously TENS devices for fibromyalgia pain. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of amantadine for the treatment of fatigue in multiple sclerosis: a systematic review and meta-analysis. [2021]

8. France pubmed.ncbi.nlm.nih.gov

[Therapeutic indications for managing symptoms: fatigue]. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Systematic review of efficacy of TENS for management of central pain in people with multiple sclerosis. [2018]

10. England 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. [2017]

11. Scotland pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation: A glimmer of hope for multiple sclerosis fatigue? [2018]

12. England pubmed.ncbi.nlm.nih.gov

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