Multiple Sclerosis
Conditions
Brief summary
In this project the investigators will be using non-invasive brain stimulation on people with multiple sclerosis (PwMS) to improve leg muscle function. Two groups of participants will be recruited. One group will perform strength testing with and without the brain stimulation. The second group of participants will perform a fatigue task, pulling against a wire at a low level of force, with and without the brain stimulation. This type of brain stimulation has been shown to transiently improve strength and fatigue measures in other populations, e.g. aged, Parkinson's, and improve cognitive abilities in people with multiple sclerosis. It is the investigator's hope that the increases in performance seen in other patient groups will also occur in people with multiple sclerosis. Future investigations will look to apply the non-invasive brain stimulation technique during physical rehabilitation to improve short and long term outcomes related to physical function.
Interventions
DEVICEtDCS
Less than 10V of Transcranial Direct Current Stimulation. Sham 0V of Transcranial Direct Current Stimulation.
Sponsors
Colorado State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
30 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Medically diagnosed with MS * Moderate disability (Patient Determined Disease Steps score 2-6) * Self-reported differences in function between the legs (2-5 on a 1-5 scale) * People with MS with physician clearance
Exclusion criteria
* A relapse of disease symptoms in the last 60 days * A condition unrelated to MS that would exacerbate fatigue, such as anemia, hypothyroidism, shiftwork-related fatigue, B12 deficiency, major sleep disorder, or major depressive disorder * Medical diagnosis or condition that makes participating in exercise training dangerous, such as major renal, pulmonary, hepatic, cardiac, gastrointestinal, HIV, cancer (other than treated basal cell cancer), other neurological disorders, or pregnancy * History of heart attack or current diagnosis of cardiovascular disease * History of seizure disorders (or on medications known to lower seizure threshold), hydrocephalus (buildup of fluid in the brain), or diabetes * Alcohol dependence or abuse (\>2 drinks/day), or present history (last six months) of drug abuse * History of significant traumatic brain injury or hydrocephalus * Pregnancy * Recent hospitalization (within the last 3 months) or enforced bed rest/sedentary state. * Presence of metal is present or implanted device or metal object that is not safe for TMS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Leg Muscle Strength With and Without tDCS. | At session 1 and minimum of 7 days later | Knee extensor strength will be tested with tDCS (less than 10V) and sham stimulation (0V). Participants performed maximal voluntary contractions (MVCs) with the knee extensors to objectively determine the weaker leg as more-affected, which was afterwards confirmed by the subject's self-report and used for the subsequent endurance task. This task consisted of a sustained isometric contraction at 15% MVC until volitional task termination and was immediately followed by a post MVC. During tDCS, stimulation intensity was ramped up to 2 mA, started 90 second prior to the task, and extended until task failure or a maximum stimulation length of 20 minutes. For Sham, the current was ramped up to 2 mA, but turned off after 30 seconds. |
| Leg Muscle Endurance With and Without tDCS. | At session 1 and minimum of 7 days later. | Knee extensor endurance (fatigue) will be tested with tDCS (less than 10V) and sham stimulation (0V), as reported as time to failure. During tDCS, stimulation intensity was ramped up to 2 mA, started 90 second prior to the task, and extended until task failure or a maximum stimulation length of 20 minutes. For Sham, the current was ramped up to 2 mA, but turned off after 30 seconds. |
| 6 Minute Walk Test | At session 1 and minimum of 7 days later | After completion of the tDCS/Sham strength assessment participants will perform a 6 minute walk test. The test will be performed in a cordoned off hallway with 2 cones placed 30 meters apart. Once the participants begin walking, a timer will be started and the distance covered every min will be recorded. Participants are allowed to stop and rest during the test if required. Every minute during the walk test participants will be asked their rating of perceived exertion (RPE, 0-10 scale). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Separated by a minimum of 7 days, participants will perform leg muscle strength and fatigue testing once with tDCS and once with Sham in a counterbalanced order.
Leg muscle strength testing will be measured by performing a series of maximal effort knee extension, knee flexion, plantar/dorsi-flexion trials. Note: the 6 minute walk test was not conducted.
The fatigue testing will be measured by time to fatigue with isometric contraction of the knee extensors.
tDCS: Less than 10V of Transcranial Direct Current Stimulation
Sham tDCS: Sham 0V of Transcranial Direct Current Stimulation | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 2 Participants | — |
| Age, Categorical Between 18 and 65 years | 12 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 11 Participants | — |
| Sex: Female, Male Male | 3 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 |
| other Total, other adverse events | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 14 | 0 / 14 |
Outcome results
Primary
6 Minute Walk Test
After completion of the tDCS/Sham strength assessment participants will perform a 6 minute walk test. The test will be performed in a cordoned off hallway with 2 cones placed 30 meters apart. Once the participants begin walking, a timer will be started and the distance covered every min will be recorded. Participants are allowed to stop and rest during the test if required. Every minute during the walk test participants will be asked their rating of perceived exertion (RPE, 0-10 scale).
Time frame: At session 1 and minimum of 7 days later
Population: No data was collected
Primary
Leg Muscle Endurance With and Without tDCS.
Knee extensor endurance (fatigue) will be tested with tDCS (less than 10V) and sham stimulation (0V), as reported as time to failure. During tDCS, stimulation intensity was ramped up to 2 mA, started 90 second prior to the task, and extended until task failure or a maximum stimulation length of 20 minutes. For Sham, the current was ramped up to 2 mA, but turned off after 30 seconds.
Time frame: At session 1 and minimum of 7 days later.
Population: Crossover design
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Study Participants | Leg Muscle Endurance With and Without tDCS. | tDCS Stimulation | 1087 seconds | Standard Error 938 |
| All Study Participants | Leg Muscle Endurance With and Without tDCS. | Sham Stimulation | 872 seconds | Standard Error 547 |
Primary
Leg Muscle Strength With and Without tDCS.
Knee extensor strength will be tested with tDCS (less than 10V) and sham stimulation (0V). Participants performed maximal voluntary contractions (MVCs) with the knee extensors to objectively determine the weaker leg as more-affected, which was afterwards confirmed by the subject's self-report and used for the subsequent endurance task. This task consisted of a sustained isometric contraction at 15% MVC until volitional task termination and was immediately followed by a post MVC. During tDCS, stimulation intensity was ramped up to 2 mA, started 90 second prior to the task, and extended until task failure or a maximum stimulation length of 20 minutes. For Sham, the current was ramped up to 2 mA, but turned off after 30 seconds.
Time frame: At session 1 and minimum of 7 days later
Population: Crossover design
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Study Participants | Leg Muscle Strength With and Without tDCS. | tDCS Stimulation | 323 Newtons | Standard Error 15 |
| All Study Participants | Leg Muscle Strength With and Without tDCS. | Sham Stimulation | 330 Newtons | Standard Error 98 |