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Principal Investigator: Dorian K Rose
Organization: VETERANS HEALTH ADMINISTRATION
Fiscal Year: 2024
Funding agency: Veterans Affairs
Background/Purpose: Physical rehabilitation of walking post-stroke is designed to improve individuals' mobility
in the presence of motor, sensory and balance impairments. Effective strategies to improve balance and
decrease fall risk continue to be a need in stroke rehabilitation. To address this, our laboratory has studied a
novel Backward Walking Training program (BWTraining) to improve both forward and backward walking speed
as well as balance in individuals with both acute and chronic stroke. Our prior published work has
demonstrated that this intervention is safe, feasible and effective, however, critical questions remain
unanswered regarding how best to deliver this intervention for optimal impact. The primary aim of this proposal
is to establish dosage effects of BWTraining for maximizing gains in forward walking speed, backward walking
speed, and dynamic balance. Additionally, we will determine baseline brain MRI predictors of response to
BWTraining intervention and explore changes in brain activity as a result of this behavioral intervention. We are
interested in understanding how individual differences in structural and functional brain measurements might
distinguish between responses to BWTraining. This information will promote prudent decision-making as to
which patients are good candidates for this novel intervention. We will conduct a randomized controlled trial
with three specific aims to test the 1) Dose effect of number of BWTraining sessions on walking speed and
balance, 2) the ability of resting state Functional Connectivity (rs-FC) between specified brain regions and
Blood Oxygen Level-Dependent (BOLD) activation of brain Regions Of Interest (ROIs) during task-based fMRI
to predict BWTraining outcomes and 3) changes in both rs-FC and BOLD activation during contralateral ankle
motion following BWTraining intervention compared to baseline.
Study Design: This is a randomized single-blind controlled trial.
Subjects: Forty-eight individuals, 2-4 months post-stroke, will meet the following study criteria: 1) ambulatory
with gait speed < 0.8 m/s; 2) community-dwelling; 3) Berg Balance Scale < 42; 4) absence of other
neurological conditions; 5) stable cardiac status; 6) absence of lower extremity orthopedic impairments or pain
that limits gait ability; 7) absence of metal and Magnetic Resonance sensitive implanted medical devices.
Methods: Following baseline Assessment A, participants will be randomized to an 18 or 27 session
BWTraining group. BWTraining intervention (3X/week for 6 or 9 weeks) consists of 20–30 minutes of step
training using a Body Weight Support and Treadmill system followed by 20 minutes of overground gait training.
Assessment B will occur after the final training session for each group. Assessment C will occur 6-weeks post-
intervention and Assessment D at six months post-intervention for both groups. Magnetic Resonance Imaging
of the brain consisting of rs-FC and BOLD blood flow in ROI's during an ankle motor task will be assessed at
Assessments A and B to address Specific Aim 2 and Specific Aim 3 respectively.
Outcome Measures: Primary outcome measure is forward gait speed. Secondary measures include backward
walking gait speed, dynamic balance measured by the Functional Gait Assessment and Center of Mass
Asymmetry, fall self-efficacy and spatial-temporal gait measures.
Data Analysis Plan: A sample size of 48 (24/group) provides 80% statistical power to detect a 0.11 m/s
difference in post-intervention gait speed between the 18- and 27-session groups at a 5% significance level
using a two-sample t-test. To assess training dose effect, a two-sample t-test will be performed on the primary
outcome, forward walking speed. The ability of rs-FC and BOLD activation of ROI's conducted pre-intervention
to predict intervention response will be assessed based on the correlation with gait speed change. Mean
connectivity strength for each network and mean signal intensity strength for each ROI will be compared pre-
to post-intervention.
Terms: <Active Follow-up><Acute><Address><Adopted><Ankle><Apoplexy><Area><Balance training><Behavior Conditioning Therapy><Behavior Modification><Behavior Therapy><Behavior Treatment><Behavioral><Behavioral Conditioning Therapy><Behavioral Mechanisms><Behavioral Modification><Behavioral Therapy><Behavioral Treatment><Blood flow><Body Weight><Brain><Brain Nervous System><Brain Vascular Accident><Brain Vascular Disorders><Brain imaging><Brain region><Cardiac><Caring><Cell Communication and Signaling><Cell Signaling><Cerebral Stroke><Cerebrovascular Apoplexy><Cerebrovascular Disease><Cerebrovascular Disorders><Cerebrovascular Stroke><Characteristics><Clinical><Clinical Trials><Communities><Conditioning Therapy><Contralateral><Data Analyses><Data Analysis><Decision Making><Dose><Education for Intervention><Educational Intervention><Effectiveness><Encephalon><Equilibrium><Evidence based practice guidelines><Functional MRI><Functional Magnetic Resonance Imaging><Gait><Gait speed><Hospital Admission><Hospitalization><Impairment><Individual><Individual Differences><Infarction><Inpatients><Instruction Intervention><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Intracranial Vascular Diseases><Intracranial Vascular Disorders><Knowledge><Laboratories><Learning><Lesion><Lower Extremity><Lower Limb><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance><Magnetic Resonance Imaging><Measurement><Measures><Mechanisms of Behavior and Behavior Change><Medical Device><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Medical Rehabilitation><Medical center><Membrum inferius><Metals><Methods><Motion><Motor><NMR Imaging><NMR Tomography><Neuro rehabilitation><Neurologic><Neurological><Neurorehabilitation><Nuclear Magnetic Resonance Imaging><Orthopedic><Orthopedic Surgical Profession><Orthopedics><Outcome><Outcome Measure><Pain><Painful><Participant><Patients><Performance><Persons><Physical Rehabilitation><Prediction of Response to Therapy><Publishing><Randomized><Randomized, Controlled Trials><Recovery><Recovery of Function><Regio tarsalis><Rehabilitation><Rehabilitation therapy><Research><Research Design><Research Resources><Resources><Rest><Sample Size><Sampling><Self Efficacy><Sensory impairment><Signal Transduction><Signal Transduction Systems><Signaling><Single-Blind Study><Single-blind><Specific qualifier value><Specified><Step retraining><Step training><Stroke><Study Type><System><Testing><Therapeutic Intervention><Training><Training Intervention><Training Programs><Veterans><Walking><Work><Zeugmatography><active followup><acute cerebrovascular accident><acute stroke><after stroke><ambulatory rehabilitation><balance><balance disorder><balance function><balance impairment><behavior intervention><behavior mechanism><behavior response><behavioral intervention><behavioral response><biological signal transduction><blood oxygen level dependent><blood oxygenation level dependent><brain MR imaging><brain MRI><brain attack><brain magnetic resonance imaging><brain vascular disease><brain vascular dysfunction><brain visualization><cerebral MR imaging><cerebral MRI><cerebral magnetic resonance imaging><cerebral vascular accident><cerebral vascular disease><cerebral vascular dysfunction><cerebrovascular accident><cerebrovascular dysfunction><chronic stroke><clinical applicability><clinical application><clinical care><clinical practice><compare intervention><comparison intervention><cost estimate><cost estimation><data interpretation><design><designing><disturbed balance><dosage><effectiveness study><equilibration disorder><equilibrium disorder><evidence based guidelines><evidence based recommendations><fMRI><fall risk><falls><follow up><follow-up><followed up><followup><functional recovery><gait recovery><gait rehab><gait rehabilitation><gait retraining><gait training><improved><improved mobility><indexing><infarct><insight><instructional intervention><interest><intervention program><intervention therapy><interventional strategy><intracranial vascular dysfunction><measurable outcome><medical implant><mobility enhancement><mobility improvement><motor impairment><motor recovery><movement impairment><movement limitation><neural network><neurological rehab><neurological rehabilitation><neurophysiological><neurophysiology><neurorehab><neurorehabilitative><novel><optimized mobility><outcome measurement><personalization of treatment><personalized medicine><personalized therapy><personalized treatment><physical rehab><post intervention><post stroke><poststroke><predict responsiveness><predict therapeutic response><predict therapy response><predicting response><primary outcome><randomisation><randomization><randomized control trial><randomly assigned><rehab research><rehab therapy><rehabilitation after stroke><rehabilitation research><rehabilitative><rehabilitative therapy><response><restoration of walking ability><secondary analysis><skills><stroke rehab><stroke rehabilitation><stroked><strokes><study design><therapeutic effectiveness><therapy prediction><train balance><treadmill><treatment prediction><treatment response prediction><walking pace><walking rehabilitation><walking speed>