Multiple Sclerosis
Conditions
Keywords
Brain Stimulation, Balance Training
Brief summary
Many people with multiple sclerosis (PwMS) have decreased balance and postural control, gait deficits, and a high frequency of falls. High fall rates and mobility impairments pose a significant risk to the independence and quality of life of PwMS. Therefore, effective interventions to improve balance and postural control are urgently needed to decrease the frequency of falls in PwMS. Balance training has been demonstrated to significantly improve postural control and gait in PwMS. One possible treatment modality to amplify the effects of balance training is transcranial direct current stimulation (tDCS), a non-invasive means to increase cortical excitability and potentially prime the brain for task specific learning. The cerebellum plays a vital role in balance and posture and may be an important target structure for tDCS studies seeking to reduce fall risk. Studies have shown that anodal cerebellar tDCS is effective in improving balance control in older adults with high fall risk and patients with chronic stroke. However, the most effective tDCS intensity and the duration of the effects on balance control has not been established. Moreover, no study has combined cerebellar tDCS and balance training to reduce fall risk in PwMS. The purpose of this study is to investigate the effects of cerebellar transcranial direct current stimulation (tDCS) on fall risk in people with relapsing-remitting multiple sclerosis. We will conduct tDCS or SHAM followed by balance training on 4 consecutive days. We will evaluate fall risk with well-established functional tasks, such as the Berg Balance Scale, Timed Up and Go (TUG), the six minute walk test (6MWT), and static posturography. Prospective participants, men and women with relapsing-remitting MS, will be recruited. To accomplish this study, 30 participants will be randomly assigned into 3 groups (2 mA tDCS, 4 mA tDCS, or SHAM). This study involves 4 daily visits at the Integrative Neurophysiology Lab at the same time of day for each subject and three follow-up visits. The duration of visit 1 will be approximately 2.5 hours and the duration of visits 2-4 will be approximately 1.5 hours. Visit 5, 6, and 7 will be approximately 24 hours, 1 week, and 3 weeks, respectively, after visit 4 and will last approximately 1.5 hours. During tDCS sessions, participants will undergo either Sham, 2 mA, and 4 mA tDCS for 20 minutes followed by balance training.
Interventions
DEVICESham Transcranial Direct Current Stimulation (tDCS)
tDCS is a non-invasive brain stimulation technique in which a very weak electrical current (2 mA) is applied to the scalp at the beginning of the session and then remains at 0 mA for the duration of the session to control for placebo-like effects. The anode and cathode will both be placed over the cerebellum.
BEHAVIORALBalance Training
The balance training protocol will include balance training exercises on both compliant (i.e., foam pad and trampoline) and firm surfaces.
tDCS is a non-invasive brain stimulation technique in which very weak electrical current (2 mA) is applied to the scalp for 20 minutes. The anode and cathode will both be placed over the cerebellum.
DEVICE4 mA Transcranial Direct Current Stimulation
tDCS is a non-invasive brain stimulation technique in which very weak electrical current (4 mA) is applied to the scalp for 20 minutes. The anode and cathode will both be placed over the cerebellum.
Sponsors
University of Iowa
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. medically diagnosed with relapsing-remitting multiple sclerosis 2. 18-70 years of age 3. moderate disability (score of 2-6 on the Patient Determined Disease Scale) 4. self-reported differences in function between legs, have fallen within the last year 5. able to walk for 6 mins, and not taking any psychoactive medication.
Exclusion criteria
1. relapse within the last 60 days 2. have changed disease modifying medications in the last 45 days 3. are currently pregnant 4. have a concurrent neurological or neuromuscular disease 5. have been hospitalized within the last 90 days 6. have any contraindications for the tDCS device (i.e., pacemakers or metal implants) 7. are unable to understand/sign the consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Score on the Berg Balance Scale | 24 hours, 2 weeks, and 4 weeks post-intervention | The BBS is a valid and reliable assessment of balance during static (e.g., standing with eyes closed) and dynamic conditions (e.g., completing a 360-degree turn) conditions. BBS scores range from 0 to 56. Lower scores indicate increased impairment in balance. A cut-off score of 44 has been established as a criterion to identify PwMS with a high fall risk. |
| Time to Complete the Timed Up and Go Test (TUG) | 24 hours, 2 weeks, and 4 weeks post-intervention | The TUG measures the time it takes for the participant to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down. Two trials were completed and the reported score is the average time between the two trials. A higher number means it took the participant more time to complete the task (i.e., worse performance). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Complete the Six Minute Walk Test (6MWT) | 24 hours, 2 weeks, and 4 weeks post-intervention | Subjects performed the 6MWT in a cordoned-off hallway with two symbols on the ground, placed 30 meters apart. Subjects were instructed to walk as far as possible between the marks for 6 minutes, walking around each symbol like a cone. Higher scores indicate more distance walked (i.e., better performance). |
| Score on the Fatigue Severity Scale (FSS) | 24 hours, 2-weeks, and 4-weeks post-intervention | The FSS consists of nine statements used to assess perceived fatigability. Subjects are asked to rate how much they felt a statement applied to them, on a 7-point scale (low value = does not apply, high value = high agreement with the statement). The questionnaire is scored by calculating the average response to the statements. Therefore, the scores will range from 1 to 7 (1 = low fatigue, 7 = high fatigue). A score ≥ 4 indicates a clinically significant level of fatigue. |
Countries
United States
Participant flow
Pre-assignment details
No participants were assigned to the 2 mA tDCS group
Participants by arm
| Arm | Count |
|---|---|
| Sham tDCS The tDCS device will perform a 30 second ramp up to 2 mA and then an immediate 30 second ramp down to 0 mA. Until the 19:30 minute time point, the tDCS will remain at 0 mA. At this time point, the tDCS will ramp up to 2 mA and then will immediately ramp back down to 0 mA.
Sham Transcranial Direct Current Stimulation (tDCS): tDCS is a non-invasive brain stimulation technique in which a very weak electrical current (2 mA) is applied to the scalp at the beginning of the session and then remains at 0 mA for the duration of the session to control for placebo-like effects. The anode and cathode will both be placed over the cerebellum.
Balance Training: The balance training protocol will include balance training exercises on both compliant (i.e., foam pad and trampoline) and firm surfaces. | 9 |
| 4 mA tDCS The participants in this group will receive tDCS at 4 mA while seated comfortably. The intensity will start at 0 mA and will be incrementally increased to the target intensity (4 mA) over the initial 30 seconds. Then, the tDCS will deliver stimulation at the target intensity until the 19:30 minute time point. At this point, the current will gradually decrease back to 0 mA.
Balance Training: The balance training protocol will include balance training exercises on both compliant (i.e., foam pad and trampoline) and firm surfaces.
4 mA Transcranial Direct Current Stimulation: tDCS is a non-invasive brain stimulation technique in which very weak electrical current (4 mA) is applied to the scalp for 20 minutes. The anode and cathode will both be placed over the cerebellum. | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Total | 4 mA tDCS | Sham tDCS |
|---|---|---|---|
| Age, Continuous | 50.57 years STANDARD_DEVIATION 11.86 | 50.57 years STANDARD_DEVIATION 14.89 | 50.57 years STANDARD_DEVIATION 11.04 |
| Berg Balance Scale | 51.73 units on a scale STANDARD_DEVIATION 8.41 | 50 units on a scale STANDARD_DEVIATION 11.56 | 53 units on a scale STANDARD_DEVIATION 4.93 |
| Fatigue Severity Scale | 4.17 units on a scale STANDARD_DEVIATION 1.5 | 3.14 units on a scale STANDARD_DEVIATION 1.36 | 4.48 units on a scale STANDARD_DEVIATION 1.68 |
| Functional Gait Assessment | 23.93 units on a scale STANDARD_DEVIATION 6.77 | 23.14 units on a scale STANDARD_DEVIATION 9.04 | 24.71 units on a scale STANDARD_DEVIATION 4.86 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 7 Participants | 8 Participants |
| Region of Enrollment United States | 18 participants | 9 participants | 9 participants |
| Sex: Female, Male Female | 12 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 3 Participants |
| Six Minute Walk Test | 460.72 meters STANDARD_DEVIATION 70.4 | 481.30 meters STANDARD_DEVIATION 35.73 | 431.51 meters STANDARD_DEVIATION 86.09 |
| Timed Up and Go | 8.42 seconds STANDARD_DEVIATION 2.55 | 8.78 seconds STANDARD_DEVIATION 3.54 | 8.15 seconds STANDARD_DEVIATION 1.55 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 0 / 7 | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
Score on the Berg Balance Scale
The BBS is a valid and reliable assessment of balance during static (e.g., standing with eyes closed) and dynamic conditions (e.g., completing a 360-degree turn) conditions. BBS scores range from 0 to 56. Lower scores indicate increased impairment in balance. A cut-off score of 44 has been established as a criterion to identify PwMS with a high fall risk.
Time frame: 24 hours, 2 weeks, and 4 weeks post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham tDCS | Score on the Berg Balance Scale | 24 hours post-intervention | 54.43 units on a scale | Standard Deviation 2.37 |
| Sham tDCS | Score on the Berg Balance Scale | 2-weeks post-intervention | 54.67 units on a scale | Standard Deviation 2.07 |
| Sham tDCS | Score on the Berg Balance Scale | 4-weeks post-intervention | 54.29 units on a scale | Standard Deviation 2.56 |
| 4 mA tDCS | Score on the Berg Balance Scale | 24 hours post-intervention | 51.43 units on a scale | Standard Deviation 9.11 |
| 4 mA tDCS | Score on the Berg Balance Scale | 2-weeks post-intervention | 50.33 units on a scale | Standard Deviation 10.21 |
| 4 mA tDCS | Score on the Berg Balance Scale | 4-weeks post-intervention | 51.17 units on a scale | Standard Deviation 9.93 |
Primary
Time to Complete the Timed Up and Go Test (TUG)
The TUG measures the time it takes for the participant to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down. Two trials were completed and the reported score is the average time between the two trials. A higher number means it took the participant more time to complete the task (i.e., worse performance).
Time frame: 24 hours, 2 weeks, and 4 weeks post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham tDCS | Time to Complete the Timed Up and Go Test (TUG) | 24 hours post-intervention | 7.81 seconds | Standard Deviation 1.66 |
| Sham tDCS | Time to Complete the Timed Up and Go Test (TUG) | 2-week post-intervention | 7.55 seconds | Standard Deviation 1.43 |
| Sham tDCS | Time to Complete the Timed Up and Go Test (TUG) | 4-weeks post-intervention | 7.10 seconds | Standard Deviation 1.23 |
| 4 mA tDCS | Time to Complete the Timed Up and Go Test (TUG) | 24 hours post-intervention | 7.47 seconds | Standard Deviation 3.78 |
| 4 mA tDCS | Time to Complete the Timed Up and Go Test (TUG) | 2-week post-intervention | 6.99 seconds | Standard Deviation 3.34 |
| 4 mA tDCS | Time to Complete the Timed Up and Go Test (TUG) | 4-weeks post-intervention | 6.88 seconds | Standard Deviation 3.1 |
Secondary
Score on the Fatigue Severity Scale (FSS)
The FSS consists of nine statements used to assess perceived fatigability. Subjects are asked to rate how much they felt a statement applied to them, on a 7-point scale (low value = does not apply, high value = high agreement with the statement). The questionnaire is scored by calculating the average response to the statements. Therefore, the scores will range from 1 to 7 (1 = low fatigue, 7 = high fatigue). A score ≥ 4 indicates a clinically significant level of fatigue.
Time frame: 24 hours, 2-weeks, and 4-weeks post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham tDCS | Score on the Fatigue Severity Scale (FSS) | 24 hours post-intervention | 4.21 units on a scale | Standard Deviation 1.38 |
| Sham tDCS | Score on the Fatigue Severity Scale (FSS) | 2-weeks post-intervention | 3.81 units on a scale | Standard Deviation 1.52 |
| Sham tDCS | Score on the Fatigue Severity Scale (FSS) | 4-weeks post-intervention | 3.60 units on a scale | Standard Deviation 1.51 |
| 4 mA tDCS | Score on the Fatigue Severity Scale (FSS) | 24 hours post-intervention | 3.62 units on a scale | Standard Deviation 2.11 |
| 4 mA tDCS | Score on the Fatigue Severity Scale (FSS) | 2-weeks post-intervention | 4.39 units on a scale | Standard Deviation 1.31 |
| 4 mA tDCS | Score on the Fatigue Severity Scale (FSS) | 4-weeks post-intervention | 3.80 units on a scale | Standard Deviation 1.64 |
Secondary
Time to Complete the Six Minute Walk Test (6MWT)
Subjects performed the 6MWT in a cordoned-off hallway with two symbols on the ground, placed 30 meters apart. Subjects were instructed to walk as far as possible between the marks for 6 minutes, walking around each symbol like a cone. Higher scores indicate more distance walked (i.e., better performance).
Time frame: 24 hours, 2 weeks, and 4 weeks post-intervention
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham tDCS | Time to Complete the Six Minute Walk Test (6MWT) | 24 hours post-intervention | 464.04 meters | Standard Deviation 107.68 |
| Sham tDCS | Time to Complete the Six Minute Walk Test (6MWT) | 2-weeks post-intervention | 479.33 meters | Standard Deviation 137.44 |
| Sham tDCS | Time to Complete the Six Minute Walk Test (6MWT) | 4-weeks post-intervention | 487.44 meters | Standard Deviation 114.1 |
| 4 mA tDCS | Time to Complete the Six Minute Walk Test (6MWT) | 24 hours post-intervention | 523.31 meters | Standard Deviation 44.7 |
| 4 mA tDCS | Time to Complete the Six Minute Walk Test (6MWT) | 2-weeks post-intervention | 542.15 meters | Standard Deviation 91.86 |
| 4 mA tDCS | Time to Complete the Six Minute Walk Test (6MWT) | 4-weeks post-intervention | 545.03 meters | Standard Deviation 104.95 |