Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Falls, Posture, Rehabilitation, Cognition, Neuroimaging
Brief summary
Falls are common in Veterans with multiple sclerosis (MS), and current rehabilitation approaches to reduce falls are inadequate. Protective step training (in which a person is exposed to repeated slips) is a promising tool to reduce falls in older adults. However, whether this approach is effective in people with MS is unknown. Investigating the effect of promising therapies, such as protective step training, will enhance our ability to treat Veterans with MS who are at risk for falls. Therefore, we will assess whether people with MS improve postural control and reduce falls through protective step training. we will also determine whether cognitive ability or brain structure can predict who will improve most. These data will inform clinical treatment strategies in people with MS at risk for falls.
Detailed description
Current rehabilitation strategies to prevent falls in people with MS are inadequate. Protective step training is a novel and promising treatment in which people are exposed to repeated slips. This training aims to improve automatic postural control including quick, protective steps, which are a critical aspect of fall avoidance, and are delayed in people with MS. This therapy has been shown to prevent falls in healthy older adults. However, the effectiveness of perturbation training in Veterans with MS is unknown. Identifying effective methods of fall prevention in people with MS, such as perturbation training, can lead to fewer falls in this population. People with MS often exhibit considerable variability in their responsiveness to rehabilitation. Said differently, improvement in performance through training is variable across individuals. The ability to predict responsiveness to treatment would be extremely beneficial for clinicians; improving the efficiency by which they provide care. Recent work suggests cognitive ability and structural brain connectivity may predict responsiveness to motor rehabilitation. However, the degree to which these characteristics predict responsiveness in people with MS is currently unknown. Therefore, the overall goals of this project are to understand 1) whether people with MS can improve postural control and reduce falls through perturbation training, and 2) whether the investigators can predict (via cognitive testing and neuroimaging), who will benefit most from treatment. The investigators will achieve these goals through three specific aims. Aim 1: identify whether people with MS can improve protective stepping, a critical skill for fall prevention, through 2 weeks of protective step training. Aim 2: determine if cognitive capacity predicts postural improvement through training in people with MS. Aim 3: determine if brain structural connectivity predicts postural improvements through training. The imaging data collected will also allow the investigators to investigate whether MS-related changes in brain connectivity contributes to postural response dysfunction. The efficacy of perturbation training in people with MS (Aim 1) will be studied by measuring protective stepping performance before and after a 2-week perturbation training protocol. In addition, the investigators will gather prospective falls data through a falls calendar over the course of 8 weeks prior to and 8 weeks after the perturbation training to gain preliminary data regarding the effect of this training on falls. To determine which baseline characteristics predict responsiveness to training (Aims 2 and 3), the investigators will also assess baseline cognitive capacity and brain structural integrity (via diffusion tensor imaging; DTI). The investigators will determine whether these baseline participant characteristics predict which participants exhibit the most improvement through the course of training. This project will provide insight into 1) the effectiveness of a promising fall prevention intervention, and 2) the ability to predict which patients will benefit most from the intervention. This knowledge will be an important step toward improving care of people with MS who are at risk for falls.
Interventions
Participants will undergo 2 weeks of training, in which they will be exposed to repeated slips on a treadmill. This approach is aimed at improving protective steps.
Sponsors
Study design
Masking description
Primary outcomes are objective (i.e. assessed via computer algorithms), thus reducing the need for masking.
Intervention model description
Multiple-baseline, within-subject design
Eligibility
Inclusion criteria
* Neurologist diagnosed MS (for MS participants only) * Ability to Stand for 5 minutes without aid * Ability to comprehend English * At risk for falls (determined via questionnaire; for MS participants only) * EDMUS score \<7 (determined by testers)
Exclusion criteria
* Any non-MS neurological pathology * Orthopedic impairments affecting balance * Previous cardiac events (stroke or heart attack)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Training-related Change in Margin of Stability | Baseline and Post-test (immediately after the intervention) | Margin of Stability is a measure of stepping effectiveness; characterized as the difference between the extrapolated center of mass and the base of support at the instance of first foot contact. The primary endpoint was the change in Margin of Stability before to after training (i.e. Baseline to Post-test). The units of this measure are in meters. Large values represent better steps. So, positive change scores represent improvement in stepping. |
| Symbol Digit Modality Test | Baseline | The Symbol Digit Modality Test (SDMT) is a cognitive assessment that probes processing speed. The score is the number of symbols and digits that one correctly matches over 90 seconds, and is assessed via paper and pencil. As such, the lower bound is 0, and there is no upper bound. Larger values are better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Training-related Changes in Reactive Step Length | Baseline and Post-test (immediately after the intervention) | Reactive Step Length is the length of the first step after the participant loses their balance. The primary endpoint was the immediate change in performance through training (i.e., initial training period; Base2-Post1). The primary endpoint was the change in Reactive Step Length before to after training (i.e., Baseline to Post-test). The units of this measure are in meters. Large values represent better steps. So, positive change scores represent improvement in stepping. |
| Training-related Change in Reactive Step Latency | Baseline and Post-test (immediately after 2 week intervention) | Reactive Step Latency is the time between when the balance perturbation occurs to lift-off of the foot. The primary endpoint was the change in performance through training (i.e., Baseline to Post-test). Smaller values represent faster (better) steps. So, negative change scores represent improvement in stepping through training. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Step Training (MS Group) This group of people with MS will undergo a baseline control period, as well as an intervention period. As such, they will serve as their own control subjects. | 27 |
| Step Training (Control Group) This group of people without MS will undergo a baseline control period, as well as an intervention period. As such, they will serve as their own control subjects. | 17 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 2 |
Baseline characteristics
| Characteristic | Step Training (MS Group) | Step Training (Control Group) | Total |
|---|---|---|---|
| Age, Continuous | 56.49 years STANDARD_DEVIATION 13.97 | 58.31 years STANDARD_DEVIATION 19.3 | 57.20 years STANDARD_DEVIATION 16.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 14 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 25 Participants | 15 Participants | 40 Participants |
| Sex: Female, Male Female | 16 Participants | 11 Participants | 27 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 17 |
| other Total, other adverse events | 0 / 27 | 0 / 17 |
| serious Total, serious adverse events | 0 / 27 | 0 / 17 |
Outcome results
Symbol Digit Modality Test
The Symbol Digit Modality Test (SDMT) is a cognitive assessment that probes processing speed. The score is the number of symbols and digits that one correctly matches over 90 seconds, and is assessed via paper and pencil. As such, the lower bound is 0, and there is no upper bound. Larger values are better.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Step Training (MS Group) | Symbol Digit Modality Test | 42.44 Units on a scale | Standard Deviation 10.33 |
| Step Training (Control Group) | Symbol Digit Modality Test | 51.88 Units on a scale | Standard Deviation 8.44 |
Training-related Change in Margin of Stability
Margin of Stability is a measure of stepping effectiveness; characterized as the difference between the extrapolated center of mass and the base of support at the instance of first foot contact. The primary endpoint was the change in Margin of Stability before to after training (i.e. Baseline to Post-test). The units of this measure are in meters. Large values represent better steps. So, positive change scores represent improvement in stepping.
Time frame: Baseline and Post-test (immediately after the intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Step Training (MS Group) | Training-related Change in Margin of Stability | 0.0289 meters | Standard Deviation 0.0777 |
| Step Training (Control Group) | Training-related Change in Margin of Stability | 0.0217 meters | Standard Deviation 0.119 |
Training-related Change in Reactive Step Latency
Reactive Step Latency is the time between when the balance perturbation occurs to lift-off of the foot. The primary endpoint was the change in performance through training (i.e., Baseline to Post-test). Smaller values represent faster (better) steps. So, negative change scores represent improvement in stepping through training.
Time frame: Baseline and Post-test (immediately after 2 week intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Step Training (MS Group) | Training-related Change in Reactive Step Latency | -0.0414 seconds | Standard Deviation 0.1047 |
| Step Training (Control Group) | Training-related Change in Reactive Step Latency | 0.0047 seconds | Standard Deviation 0.05 |
Training-related Changes in Reactive Step Length
Reactive Step Length is the length of the first step after the participant loses their balance. The primary endpoint was the immediate change in performance through training (i.e., initial training period; Base2-Post1). The primary endpoint was the change in Reactive Step Length before to after training (i.e., Baseline to Post-test). The units of this measure are in meters. Large values represent better steps. So, positive change scores represent improvement in stepping.
Time frame: Baseline and Post-test (immediately after the intervention)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Step Training (MS Group) | Training-related Changes in Reactive Step Length | 0.026 meters | Standard Deviation 0.086 |
| Step Training (Control Group) | Training-related Changes in Reactive Step Length | 0.023 meters | Standard Deviation 0.063 |