Multiple Sclerosis
Conditions
Keywords
multiple sclerosis, physical therapy, white matter integrity, neuroproprioceptive facilitation, inhibition, functional recovery, network reorganization, neurohormones, dehydroepiandrosterone
Brief summary
This study investigates whether neuroproprioceptive facilitation, inhibition physical therapy induces plastic and adaptive processes of the CNS (white matter integrity changes), if they relate to clinical improvement, and whether therapeutic effect differs between different kinds of therapies.
Detailed description
In the Multi-Arm Parallel-Group Exploratory Trial, patients with multiple sclerosis were divided into three groups by an independent study coordinator, and underwent three kinds of neuroproprioceptive facilitation, inhibition physical therapy. At baseline and after the end of the two months' therapeutic program, a blinded assessor evaluated clinical outcomes and data from DTI .
Interventions
BEHAVIORALMotor program activating therapy
Pacients underwent two months' therapy consisted of 16 face-to-face sessions (1 hour, twice a week for two months).
BEHAVIORALVojta's reflex locomotion
Pacients underwent two months' therapy consisted of 16 face-to-face sessions (1 hour, twice a week for two months).
BEHAVIORALFunctional electric stimulation
Pacients uderwent two months' therapy. They used the whole time Functional electric stimulation during activities of daily living and underwent 2 individual sessions of Motor program activating therapy.
Sponsors
Charles University, Czech Republic
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
* prevailed spastic paraparesis, stable clinical status and treatment in the preceding 3 months determined by neurologist, * Expanded Disability Status Scale score (EDSS) max. 7.5
Exclusion criteria
* other neurological disease or conditions disabling movement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| White Matter Integrity | 2 months | Magnetic resonance imaging on a 3T magnetic resonance scanner (Siemens Trio Tim, Erlangen, Germany) using a 12-channel phased-array head coil. A diffusion tensor was fitted to each voxel of the brain, and a fractional anisotropy (FA) map was created for each subject. The images were further analyzed using tract-based spatial statistics (TBSS). Fractional anisotropy (FA) is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. FA is a measure often used in diffusion imaging where it is thought to reflect fiber density, axonal diameter, and myelination in white matter. The FA is an extension of the concept of eccentricity of conic sections in 3 dimensions, normalized to the unit range. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Berg Balance Scale, BBS | 2 months | 14 items objective measure of static balance and risk of falls (0 the best, 56 the worse) |
| Timed up and go Test, TUG | 2 months | time necessary to stand up, go 3 meters, turn around, go back and sit to chair (longer time in seconds is worse function) |
| the 12-item Multiple Sclerosis Walking Scale, MSWS - 12 | 2 months | The Multiple Sclerosis Walking Scale is a self-assessment scale which measures the impact of MS on walking. It consists of 12 questions concerning the limitations to walking due to MS during the past 2 weeks. Each item can be answered with 5 options, with 1 meaning no limitation and 5 extreme limitation. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores. |
| the 29-item Multiple Sclerosis Impact Scale, MSIS -29 | 2 months | a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 not at all to 5extremely. Each of the two scales are scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates greater impact of disease on daily function (worse health). |
Participant flow
Recruitment details
Recruitment was realized between May 2015 and May 2017 at Department of Neurology, Facuty Hospital Royal Vineyard. MS patients were divided into three groups by an independent study coordinator according to availability of each therapist (in Groups 1 and 2) and amount of FES devices to borrow (in Group 3), and underwent three kinds of PT.
Pre-assignment details
120 people were initially assessed for eligibility. 24 people did not fit to inclusion criteria, 1 did decline to participate and 1 injured. 92 were allocated into three groups.
Participants by arm
| Arm | Count |
|---|---|
| Motor Program Activating Therapy MPAT is method developed and verified by our team. In this therapy, patients are corrected into a postural position where the joints are functionally centered. Somatosensory (manual and verbal) stimuli are then applied to activate motor programs in the brain, which then lead to the co-contraction of the patient's whole body when laying, sitting, standing up or moving forward.
16 face-to-face sessions (1 hour, twice a week for two months). Group 3 used the whole time Functional electric stimulation during activities of daily living and underwent 2 individual sessions. | 42 |
| Vojta's Reflex Locomotion VRL is a standard approach for patients with MS in the Czech Republic. In the therapy, global patterns of the reflex locomotion are activated by stimulation of specific zones, with the individual placed in a precisely determined initial position (supine, prone and side laying, low kneeling position).
16 face-to-face sessions (1 hour, twice a week for two months). Group 3 used the whole time Functional electric stimulation during activities of daily living and underwent 2 individual sessions. | 29 |
| Functional Electric Stimulation Functional electric stimulation in the postural corrected position was developed at our workplace. Participants first underwent individual two-hour session consisting of postural correction using MPAT and the device (The WalkAide® System, Innovative Neurotronics Inc., 4999 Aircenter Circle, Suite 103 Reno, NV 89502, USA) programming (28). Patients received the device to use as much as they felt they were able to during their normal daily living activities thereafter.
Patients used the whole time Functional electric stimulation during activities of daily living and underwent 2 individual sessions. | 21 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 7 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 8 | 3 |
Baseline characteristics
| Characteristic | Motor Program Activating Therapy | Vojta's Reflex Locomotion | Functional Electric Stimulation | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants | 29 Participants | 21 Participants | 92 Participants |
| Age, Continuous | 51 years STANDARD_DEVIATION 10.7 | 42.3 years STANDARD_DEVIATION 10.5 | 46.15 years STANDARD_DEVIATION 10.1 | 48.11 years STANDARD_DEVIATION 11 |
| EDSS | 4 units on a scale | 4 units on a scale | 4 units on a scale | 4 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 29 Participants | 21 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| length of disease | 14.2 years STANDARD_DEVIATION 7.4 | 8.38 years STANDARD_DEVIATION 5.1 | 13.15 years STANDARD_DEVIATION 6.1 | 12.72 years STANDARD_DEVIATION 7 |
| Region of Enrollment Czechia | 35 participants | 13 participants | 13 participants | 61 participants |
| Sex: Female, Male Female | 30 Participants | 19 Participants | 12 Participants | 61 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 9 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 42 | 0 / 21 |
| other Total, other adverse events | 0 / 29 | 0 / 42 | 0 / 21 |
| serious Total, serious adverse events | 0 / 29 | 0 / 42 | 1 / 21 |
Outcome results
Primary
White Matter Integrity
Magnetic resonance imaging on a 3T magnetic resonance scanner (Siemens Trio Tim, Erlangen, Germany) using a 12-channel phased-array head coil. A diffusion tensor was fitted to each voxel of the brain, and a fractional anisotropy (FA) map was created for each subject. The images were further analyzed using tract-based spatial statistics (TBSS). Fractional anisotropy (FA) is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. FA is a measure often used in diffusion imaging where it is thought to reflect fiber density, axonal diameter, and myelination in white matter. The FA is an extension of the concept of eccentricity of conic sections in 3 dimensions, normalized to the unit range.
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motor Program Activating Therapy | White Matter Integrity | 0.5023 score on a scale | Standard Deviation 0.0293 |
| Vojta's Reflex Locomotion | White Matter Integrity | 0.5168 score on a scale | Standard Deviation 0.0266 |
| Functional Electric Stimulation | White Matter Integrity | 0.4747 score on a scale | Standard Deviation 0.0293 |
Secondary
Berg Balance Scale, BBS
14 items objective measure of static balance and risk of falls (0 the best, 56 the worse)
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motor Program Activating Therapy | Berg Balance Scale, BBS | 49.79 score on a scale | Standard Deviation 8.1 |
| Vojta's Reflex Locomotion | Berg Balance Scale, BBS | 47.92 score on a scale | Standard Deviation 9.8 |
| Functional Electric Stimulation | Berg Balance Scale, BBS | 32.76 score on a scale | Standard Deviation 11.2 |
Secondary
the 12-item Multiple Sclerosis Walking Scale, MSWS - 12
The Multiple Sclerosis Walking Scale is a self-assessment scale which measures the impact of MS on walking. It consists of 12 questions concerning the limitations to walking due to MS during the past 2 weeks. Each item can be answered with 5 options, with 1 meaning no limitation and 5 extreme limitation. A total score can be generated and transformed to a 0 to 100 scale by subtracting the minimum score possible (12) from the patient's score, dividing by the maximum score possible minus the minimum possible (60-12 or 48), and multiplying the result by 100. Walking improvement on the MSWS-12 is indicated by negative change scores.
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motor Program Activating Therapy | the 12-item Multiple Sclerosis Walking Scale, MSWS - 12 | 61.57 score on a scale | Standard Deviation 12.7 |
| Vojta's Reflex Locomotion | the 12-item Multiple Sclerosis Walking Scale, MSWS - 12 | 59.77 score on a scale | Standard Deviation 18.4 |
| Functional Electric Stimulation | the 12-item Multiple Sclerosis Walking Scale, MSWS - 12 | 73.94 score on a scale | Standard Deviation 20.2 |
Secondary
the 29-item Multiple Sclerosis Impact Scale, MSIS -29
a 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on day-to-day life in the past two weeks. All items have 5 response options: 1 not at all to 5extremely. Each of the two scales are scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates greater impact of disease on daily function (worse health).
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motor Program Activating Therapy | the 29-item Multiple Sclerosis Impact Scale, MSIS -29 | 32.93 score on a scale | Standard Deviation 8.7 |
| Vojta's Reflex Locomotion | the 29-item Multiple Sclerosis Impact Scale, MSIS -29 | 33.38 score on a scale | Standard Deviation 13.3 |
| Functional Electric Stimulation | the 29-item Multiple Sclerosis Impact Scale, MSIS -29 | 43.47 score on a scale | Standard Deviation 12.6 |
Secondary
Timed up and go Test, TUG
time necessary to stand up, go 3 meters, turn around, go back and sit to chair (longer time in seconds is worse function)
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motor Program Activating Therapy | Timed up and go Test, TUG | 10.15 sec | Standard Deviation 5.8 |
| Vojta's Reflex Locomotion | Timed up and go Test, TUG | 10.31 sec | Standard Deviation 5.6 |
| Functional Electric Stimulation | Timed up and go Test, TUG | 16.88 sec | Standard Deviation 10.8 |