Transcranial Direct Current Stimulation and Walking in Multiple Sclerosis

Can Transcranial Direct Stimulation Improve Walking in Multiple Sclerosis?

Weakness on one side of the body is a hallmark of Multiple Sclerosis (MS), which has been determined to be a significant cause of progressive worsening of walking abilities. Currently, there are no efficient rehabilitation strategies available to target strength asymmetries and walking impairments. Many of the current treatments, including pharmaceuticals, are only mildly effective and are often very expensive. Thus, the development of practical, inexpensive, and effective adjunct treatments is needed.

The study is to examine the efficacy of different tDCS protocols at improving walking in PwMS. Although the details of the studies slightly vary, the global aspects of the experimental procedures are identical with the exception that the tDCS stimulation parameter timing differs between the groups. The study will be double-blind, sham-controlled, randomized cross-over design.

Maximal voluntary contractions (MVCs) of the right and left knee extensors, knee flexors, hip flexors, and dorsiflexors will be performed to determine the more-affected leg.

The study compromises 2 groups of subjects which will attend the lab for three sessions. In the first session subjects will be consented, complete the PDDS, the Fatigue Severity Scale (FSS), and a 6 minute walk test (6-MWT) for baseline performance. The second session will involve a 6 MWT performed in association with 2 conditions. Group 1: DURINGtDCS, DURINGSHAM. Group 2: BEFOREtDCS, BEFORESHAM. The conditions in each group will be in a randomized order. Intensity of tDCS will be 2mA for both groups. Group 1 will receive the conditions during the 6 MWT. tDCS for 6 min has been shown to be sufficient to induce cortical excitability. Group 2 will receive 13 min of tDCS or sham, which results in after effects lasting through the completion of the 6 MWT. tDCS will be applied to the motor cortex (M1) corresponding to the more-affected leg either before or during the 6 min walk test

Study Overview

• Status: Completed
• Conditions: Transcranial Direct Current Stimulation
• Intervention / Treatment: Device: tDCS; Device: SHAM

Detailed Description

Prospective participants, men and women with MS, will be recruited. To accomplish this study, each of the two groups of participants will need to complete 3 sessions at the INPL, each separated by 5-8 days. The duration of each session will be approximately one hour. The investigators expect data collection to last 6 months.

The study compromises 2 groups of subjects which will attend the lab for three sessions. In the first session subjects will be consented, complete the Patient Determined Disease Steps (PDDS) questionnaire, the Fatigue Severity Scale (FSS), and a 6MWT for baseline performance. The second session will involve a 6 MWT performed in association with 2 conditions. Group 1: DURING_tDCS, DURING_SHAM. Group 2: BEFORE_tDCS, BEFORE_SHAM. tDCS will be applied first follwed by SHAM in each group. Intensity of tDCS will be 2mA for both groups. Group 1 will receive the conditions during the 6 MWT. tDCS for 6 min has been shown to be sufficient to induce cortical excitability. Group 2 will receive 13 min of tDCS or sham which results in after effects lasting through the completion of the 6MWT. tDCS will be applied to the motor cortex (M1)corresponding to the more-affected leg either before or during the 6 min walk test. Leg strength, 6 MWT, and tDCS: Maximal voluntary contractions (MVCs) of the right and left knee extensors, knee flexors, hip flexors, and dorsiflexors will be performed to determine the more-affected leg. When leg strength difference is less than 10%, the more affected side will be based on self-report. For the 6 MWT, participants will be asked to walk as far as they can in 6 minutes. The 6 MWT is well established in MS research and, in order to measure fatigability as a secondary outcome, the literature suggest using a 6MWT rather than a 2MWT.Participants will walk in a cordoned off hallway between two cones placed approximately 30 meters apart. The primary outcome measure will be the distance covered in the 6 MWT. Since the investigators hypothesize that tDCS will alter the utilization of their more-affected leg, standard gait metrics during the 6MWT including gait speed, cadence, stride length and time, step length and time will be assessed with inertial sensors (OPAL system) for tDCS and SHAM (secondary outcomes). Furthermore, the investigators will calculate the distance walked index (DWI, distance Min 1 - distance Min 6), which is an objective measure of fatigability. A tDCS device (ActivaDose II) will deliver a small direct current through two sponge surface electrodes (5cm × 5cm,soaked with 15 mM NaCL). The positive electrode will be placed over the motor cortex representation of the more affected leg, and a second electrode will be placed on the forehead above the contralateral orbit. The following sessions will be performed in randomized order. Group 1 (During) - (A) The participant will receive tDCS or SHAM throughout the walking. In the tDCS trial the intensity will start at 0 mA and will be increased to 2mA over a 30 second period of time. At the 6:30 minute time point (immediately after walking) the current will gradually be reduced from 2 mA to 0 mA. (B) In the sham condition the participants will only receive the initial 30 seconds of stimulation, after which the current will be set to 0. Group 2 (Before) - (C) After a 30s ramp-up, tDCS will be delivered for 13 minutes at an intensity of 2 mA before the 6 min walk test. At the 13:00 minute time point the current will gradually be reduced from 2 mA to 0 mA. (D) Participants who undergo a sham condition will only receive the initial 30 seconds of ramp-up, after which the current will be set to 0 (D). In session 3, the condition not performed during session 2 will be performed. E.g., if a patient in Group 1 was randomly assigned DURING_SHAM for session 2, the patient will perform DURING_tDCS in session 3. All other testing conditions will be the same as session 2.

There will be no long-term follow up.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• medically diagnosed with Multiple Sclerosis,
• moderate disability (Patient Determined Disease Steps (PDDS) core 2-6), -self-- reported differences in function between legs, able to walk for 6min. -

Exclusion Criteria:

• relapse within last 60 days,
• high risk for cardiovascular disease (ACSM risk classification),
• changes in disease modifying medications within last 45 days,
• concurrent neurological/neuromuscular disease,
• hospitalization within last 90 days,
• diagnosed depression, inability to understand/sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Before Walking tDCS first then SHAM; To investigate the effects of tDCS applied before walking versus during to evaluate effectiveness of the intervention.	Device: tDCS; Brain Stimulation; Device: SHAM; Placebo device
Experimental: During Walking tDCS first then SHAM; To investigate the effects of tDCS applied before walking versus during to evaluate effectiveness of the intervention.	Device: tDCS; Brain Stimulation; Device: SHAM; Placebo device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distance Walked on a Treadmill With tDCS	6 min walk test	one week
Distance Walked on a Treadmill With SHAM	6 min walk test	one week

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leg Strength Data	Leg extensor strength and Leg flexor strength data were obtained but have not been used for data analysis.	one week

Collaborators and Investigators

• Sponsor: Thorsten Rudroff
• Investigators: Principal Investigator: Thorsten Rudroff, University of Iowa

Publications and helpful links

General Publications

• Workman CD, Kamholz J, Rudroff T. Transcranial Direct Current Stimulation (tDCS) to Improve Gait in Multiple Sclerosis: A Timing Window Comparison. Front Hum Neurosci. 2019 Nov 28;13:420. doi: 10.3389/fnhum.2019.00420. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): July 7, 2019
• Study Completion (Actual): July 7, 2019

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: November 26, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Multiple Scerosis
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis
• Other Study ID Numbers: 201810705

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
• product manufactured in and exported from the U.S.: Yes