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Protective Stepping in People With MS

Effects of Protective Step Training in People With Multiple Sclerosis

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03551665
Acronym
PRO-STEP
Enrollment
57
Registered
2018-06-11
Start date
2019-02-22
Completion date
2024-08-01
Last updated
2025-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Sclerosis

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

VA Office of Research and Development
Lead SponsorFED
Arizona State University
CollaboratorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

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

Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
Yes

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

MeasureTime frameDescription
Training-related Change in Margin of StabilityBaseline 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 TestBaselineThe 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

MeasureTime frameDescription
Training-related Changes in Reactive Step LengthBaseline 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 LatencyBaseline 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

ArmCount
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
Total44

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyLost to Follow-up112

Baseline characteristics

CharacteristicStep Training (MS Group)Step Training (Control Group)Total
Age, Continuous56.49 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 Participants3 Participants3 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
27 Participants14 Participants41 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants1 Participants
Race (NIH/OMB)
Black or African American
2 Participants0 Participants2 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants1 Participants1 Participants
Race (NIH/OMB)
White
25 Participants15 Participants40 Participants
Sex: Female, Male
Female
16 Participants11 Participants27 Participants
Sex: Female, Male
Male
11 Participants6 Participants17 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 270 / 17
other
Total, other adverse events
0 / 270 / 17
serious
Total, serious adverse events
0 / 270 / 17

Outcome results

Primary

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

ArmMeasureValue (MEAN)Dispersion
Step Training (MS Group)Symbol Digit Modality Test42.44 Units on a scaleStandard Deviation 10.33
Step Training (Control Group)Symbol Digit Modality Test51.88 Units on a scaleStandard Deviation 8.44
Comparison: We correlated cognition (SDMT; above) to the improvement in performance (margin of stability) to to determine whether cognition predicted improvement in stepping outcomes.p-value: 0.92Spearman Correlation
Primary

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)

ArmMeasureValue (MEAN)Dispersion
Step Training (MS Group)Training-related Change in Margin of Stability0.0289 metersStandard Deviation 0.0777
Step Training (Control Group)Training-related Change in Margin of Stability0.0217 metersStandard Deviation 0.119
Comparison: These data are the immediate improvements (base 2 - post 1) in the MS group.p-value: 0.03695% CI: [0.002, 0.056]Regression, Linear
Secondary

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)

ArmMeasureValue (MEAN)Dispersion
Step Training (MS Group)Training-related Change in Reactive Step Latency-0.0414 secondsStandard Deviation 0.1047
Step Training (Control Group)Training-related Change in Reactive Step Latency0.0047 secondsStandard Deviation 0.05
Comparison: We assessed the change in reactive step latency before (Baseline 2) to immediately after (post 1) training in the MS groupp-value: 0.01295% CI: [-0.073, -0.009]Regression, Linear
Secondary

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)

ArmMeasureValue (MEAN)Dispersion
Step Training (MS Group)Training-related Changes in Reactive Step Length0.026 metersStandard Deviation 0.086
Step Training (Control Group)Training-related Changes in Reactive Step Length0.023 metersStandard Deviation 0.063
Comparison: We assessed the change in reactive step length before (Baseline 2) to immediately after (post 1) training in the MS groupp-value: 0.11995% CI: [-0.007, 0.059]Regression, Linear

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026