Transcranial Direct Current Stimulation and Walking in Multiple Sclerosis
Condition: Transcranial Direct Current Stimulation
MeSH terms: Multiple Sclerosis
Study type: Interventional

Summary: 
      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
    

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.
    

Intervention name(s): tDCS; SHAM
Intervention type(s): Device; Device
Intervention description(s): Brain Stimulation; Placebo device
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: This study employed a double-blind, sham-controlled, parallel-randomized crossover design. Each participant attended three sessions. In the first session, participants were consented and completed the Patient-Determined Disease State and Fatigue Severity Scale questionnaires. Then, after a counter-balanced randomization into BEFORE or DURING groups, the participants completed a 6-Minute Walk Test for baseline/familiarization purposes. The second and third sessions involved brain stimulation or sham stimulation either before or during a 6-Minute Walk Test, depending on group assignment. The brain stimulation was randomly assigned to either session two or three, and sham stimulation was performed in the other session.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Multiple Scerosis