Reducing Fatigue in People With Multiple Sclerosis by Treatment With TENS

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Device: Transcutaneous electrical nerve stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Roger Enoka, PhD; Phone Number: 3034927232; Email: enoka@colorado.edu

Study Locations

• United States
  • Colorado
    • Boulder, Colorado, United States, 80309
      • Recruiting
      • University of Colorado
      • Contact: Roger Enoka; Phone Number: 303-492-7232; Email: enoka@colorado.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Effective dose; • 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; Electrical stimulation applied over selected leg muscle will activate sensory receptors that will transmit signals back into the central nervous system.
Sham Comparator: Sham dose; • 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; Electrical stimulation applied over selected leg muscle will activate sensory receptors that will transmit signals back into the central nervous system.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder

Publications and helpful links

General Publications

• Enoka RM, Almuklass AM, Alenazy M, Alvarez E, Duchateau J. Distinguishing between Fatigue and Fatigability in Multiple Sclerosis. Neurorehabil Neural Repair. 2021 Nov;35(11):960-973. doi: 10.1177/15459683211046257. Epub 2021 Sep 28.
• Almuklass AM, Davis L, Hamilton LD, Hebert JR, Alvarez E, Enoka RM. Pulse Width Does Not Influence the Gains Achieved With Neuromuscular Electrical Stimulation in People With Multiple Sclerosis: Double-Blind, Randomized Trial. Neurorehabil Neural Repair. 2018 Jan;32(1):84-93. doi: 10.1177/1545968317753681. Epub 2018 Jan 24.
• Almuklass AM, Capobianco RA, Feeney DF, Alvarez E, Enoka RM. Sensory nerve stimulation causes an immediate improvement in motor function of persons with multiple sclerosis: A pilot study. Mult Scler Relat Disord. 2020 Feb;38:101508. doi: 10.1016/j.msard.2019.101508. Epub 2019 Nov 6.
• Alenazy M, Daneshgar Asl S, Petrigna L, Feka K, Alvarez E, Almuklass AM, Enoka RM. Treatment with electrical stimulation of sensory nerves improves motor function and disability status in persons with multiple sclerosis: A pilot study. J Electromyogr Kinesiol. 2021 Dec;61:102607. doi: 10.1016/j.jelekin.2021.102607. Epub 2021 Oct 13.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2023
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): November 30, 2028

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 15, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2024
• Last Update Submitted That Met QC Criteria: December 5, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 22-0394

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes