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

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.

Study Overview

• Status: Withdrawn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

Detailed Description

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.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Augmented TENS; Transcutaneous electrical nerve stimulation applied to each leg separately while participants perform steady submaximal contractions.	Device: Transcutaneous electrical nerve stimulation; Commercially available device will be used to apply weak electrical currents to arm and leg muscles in each of 18 treatment sessions.; Other Names: Sham transcutaneous electrical nerve stimulation
SHAM_COMPARATOR: Sham; 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; Commercially available device will be used to apply weak electrical currents to arm and leg muscles in each of 18 treatment sessions.; Other Names: Sham transcutaneous electrical nerve stimulation

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University of Colorado, Boulder
• Collaborators: University of Colorado, Denver; Colorado State University
• Investigators: Principal Investigator: Roger Enoka, PhD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2020
• Primary Completion (ANTICIPATED): December 1, 2024
• Study Completion (ANTICIPATED): June 1, 2025

Study Registration Dates

• First Submitted: August 24, 2018
• First Submitted That Met QC Criteria: September 21, 2018
• First Posted (ACTUAL): September 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 6, 2020
• Last Update Submitted That Met QC Criteria: November 4, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: fatigue; walking; balance
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Fatigue
• Other Study ID Numbers: UColoradoBoulder2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share the data obtained by individual participants.

Drug and device information, study documents

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