The Sensorimotor Locus of Balance Control in Elderly Gait
Phase: NA
Conditions: Ambulation Difficulty, Gait, Unsteady, Fall, Position Sense Disorders
Sponsor: University of North Carolina, Chapel Hill

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PROTOCOL TEMPLATE: INTERVENTIONAL STUDY (PILOT) 
 
 
Complete Title: The sensorimotor locus of balance control in elderly gait 
 
 
Short Title: Optical flow perturbation training 
FDA IND/IDE (if applicable): Not Applicable.  
Sponsor: National Institutes of Health (Investigator Initiated) 
Protocol Date: September 1, 2017 
NCT Number: NCT03341728 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Principal Investigator (Jason R. Franz) 
328 Taylor Hall 
Chapel Hill, NC 27514 
Phone 919-966-6119 
email: jrfranz@email.unc.edu 
 
PROTOCOL TITLE:  
The sensorimotor locus of balance control in elderly gait 
Short Title:  
Optical flow perturbation training 
Lead Investigator: 
Jason R. Franz, Ph.D. 
 University of North Carolina at Chapel Hill 
Version Date: September 1, 2017 
 
I confirm that I have read this protocol and understand it.    
Principal Investigator Name:  
 
 
Jason R. Franz  
 
 
 
Principal Investigator Signature:  
 
 
 
 
 
 
 
Date:   
 
 
 
 
 
September 2017 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
Protocol Synopsis ........................................................................................................... 4 
1 
BACKGROUND  AND RATIONALE.................................................................................................................... 6 
2 
STUDY OBJECTIVES ......................................................................................................................................... 7 
3 
INVESTIGATIONAL PLAN ................................................................................................................................. 7 
4 
STUDY PROCEDURES ...................................................................................................................................... 8 
5 
STUDY EVALUATIONS AND MEASUREMENTS ................................................................................................ 8 
6 
STATISTICAL CONSIDERATIONS ...................................................................................................................... 8 
7 
STUDY INTERVENTION (DEVICE OR OTHER INTERVENTION) ......................................................................... 9 
9 
SAFETY MANAGEMENT .................................................................................................................................. 9 
10  DATA COLLECTION AND MANAGEMENT ........................................................................................................ 9 
11 RECRUITMENT STRATEGY ............................................................................................................................ 10 
12 CONSENT PROCESS ...................................................................................................................................... 10 
13 PUBLICATION................................................................................................................................................ 10 
14 REFERENCES ................................................................................................................................................. 10 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SYNOPSIS 
 
Study Title 
The sensorimotor locus of balance control in elderly gait 
Funder 
National Institutes of Health 
Clinical Phase 
Pilot 
Study Rationale 
One third of adults age 65 and older fall annually with 20-30% of falls 
resulting in serious injuries. In 2009 alone, falls in older adults resulted in 
nearly 2.2 million emergency room visits. In 2000, direct medical cost of 
non-fatal falls in adults over age 65 was $19 billion, and in 2007 that cost 
was projected to increase to $54.9 billion/year by 2020. However, despite 
considerable efforts, falls rates over this time have been highly resistant 
to change. Thus, there is a critical need for more effective diagnostic 
efforts to identify older adults at risk of falls and rehabilitative efforts to 
successfully mitigate that risk once identified. Consistent with studies on 
the postural control of standing, our recent findings suggest that older 
adults prioritize visual feedback to control balance in walking. 
Accordingly, older adults are more susceptible than young adults to 
optical flow perturbations applied in the safety of virtual reality (VR). 
These perturbations elicit the visual perception of walking instability, and 
provide the opportunity to practice walking balance corrections in a 
controlled environment. The purpose of this proof of concept study is to 
investigate the propensity for time-dependent tuning of walking balance 
control and the presence of aftereffects in older adults following a single 
session of optical flow perturbation training. 
Study Objective(s) 
To investigate the propensity for time-dependent tuning of walking 
balance control and the presence of aftereffects in older adults following 
a single session of optical flow perturbation training. 
Test Article(s) 
(If Applicable) 
Mediolateral (ML; i.e., side-to-side) optical flow perturbations applied 
during treadmill walking using a projection-based virtual reality system. 
Study Design 
 
A randomized, crossover design that included a control session of normal 
unperturbed walking and an experimental session that incorporated 
mediolateral optical flow perturbations during walking. 
Subject Population 
key criteria for Inclusion 
and Exclusion: 
Inclusion Criteria 
1. Subjects Age 65+ years 
2. Be able to walk without an assistive aid (i.e., walker, cane) 
3. Have the full capacity to provide informed consent 
Exclusion Criteria 
1. Current lower extremity injury or fracture 
2. Taking medication that causes dizziness 
3. Have a leg prosthesis 
4. Prisoners 
5. Individuals lacking the capacity to provide informed consent 

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Number of Subjects  
 
Up to 20 
Study Duration 
Each subject will participate in two sessions, each lasting up to three (3) 
hours and separated by at least one week.  
The entire study is expected to last two years (approximately one year 
for data collection and another one year for data analysis) 
Study Phases 
Screening 
Study Treatment 
Follow-Up   
 (1) Screening: We will use an initial telephone screening (attached) to 
evaluate basic study eligibility. Subjects that meet inclusion/exclusion 
criteria following phone screening will be invited to participate in the 
study. 
(2) Balance training: Subjects that provide written informed consent will 
participate in the cross-over design that includes one control session and 
one session of perturbation training, separated by at least one week. 
Efficacy Evaluations 
Primary outcome measures:  
(1) Change in Postural Sway 
(2) Change in kinematic (step width) variability 
(3) Change in foot placement targeting accuracy 
Secondary outcome measures: 
(1) Change in Cognitive-motor Interference Accuracy 
(2) Change in Cognitive-motor Interference Response Time After 10 Min 
of Walking 
(3) Change in Margin of Stability Variability After 10 Min of Walking 
Statistical Analysis Plan 
A one-way, repeated-measures analysis of variance will test for effects of 
time on dependent variables collected from each session. Significance 
will be defined using an alpha level of 0.05. 
DATA AND SAFETY 
MONITORING PLAN 
This study does not meet the criteria for an independent DSMP. The PI 
(Dr. Franz) will oversee all conduct to ensure the safety of all participants 
and the integrity of the data. At least one research staff member will be 
monitoring the subjects' movement patterns during the data collection. If 
the subject experiences any discomfort, the data collection will be 
stopped immediately. If any member of the research team encounters 
unanticipated problems (including by not limited to adverse events), we 
will make necessary adjustments to the protocol and, where appropriate, 
report these events to University administrative personnel.  
 
 
 
 
 
 

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1 
BACKGROUND AND RATIONALE 
1.1 
Introduction 
Older adults are at an exceptionally high risk of debilitating falls, contributing significantly to reduced 
independence and quality of life. Despite conventional diagnostic and rehabilitative efforts, one-third 
of people over age 65 fall annually and 20-30% of these falls lead to moderate to severe injury. When 
adjusted for inflation, annual direct medical costs from non-fatal falls in older adults are expected to 
reach $67.7 billion by 2020. Moreover, three decades of falls prevention research have led to present 
guidelines that include recommendations for targeted exercise interventions. However, most of the 
programs evaluated during this time only modestly influenced the sizeable portion of our aging 
population experiencing one or more falls annually. Unfortunately, our society now faces a growing 
dilemma – evidence suggests that the rate of injurious falls is accelerating, with 2.4 million emergency 
department visits in 2011, up 46% from 2001 despite only a 17% increase in the older adult population. 
 
There is a growing appreciation that interventions designed to challenge balance are those most likely 
to have positive impact on balance integrity. Unfortunately, conventional interventions based on this 
premise elicit only modest improvements unlikely to impact the high prevalence of falls. Our research 
group is at the forefront of using optical flow perturbations applied during walking in the safety of 
virtual reality (VR) to elicit the visual perception of instability during walking. The purpose of this proof-
of-concept study is to evaluate change in walking balance in older adults responding to a single session 
of optical flow perturbation training compared to a control session of normal walking.  
 
1.2 
Name and Description of Investigational Product or Intervention  
Optical flow perturbation system and 
paradigm: Subjects walk on a treadmill 
surrounded by a semicircular curved 
screen on which a speed-matched virtual 
hallway is projected. To this motion, the 
system adds pseudo-random mediolateral 
(ML, side-to-side) oscillations of the virtual 
hallway, designed to elicit the visual 
perception of lateral instability.  
 
 
 
1.3 
Relevant Literature and Data 
The investigators have a significant history 
of testing the effects of optical flow perturbations on walking balance in young and older adults and in 
patients with multiple sclerosis. Our cumulative evidence from these studies (listed below) 
demonstrate that older adults are significantly more susceptible to these perturbations than young 
Figure 1. System and disproportionate effects in older versus young adults. 

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adults (Fig. 1). Accordingly, we now know that this environment uniquely disrupts walking balance in 
older adults, thereby providing an opportunity to “practice” corrective motor adjustments relevant to 
preserving balance.  
 
2 
STUDY OBJECTIVE  
The purpose of this proof-of-concept study is to evaluate change in walking balance in older adults 
responding to a single session of optical flow perturbation training compared to a control session of 
normal walking.  
 
2.1 
Primary Objective 
Quantify the time-dependent changes in metrics of walking balance in older adults after walking with 
optical flow perturbations. 
 
2.2 
Secondary Objective 
Contrast effects of walking with optical flow perturbations to those of normal treadmill walking.  
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INVESTIGATIONAL PLAN (brief overview) 
 
3.1 
Study Design 
(Session A: Normal walking, Session B: Continuous optical flow perturbations). In a randomized cross-
over designed (assigned at enrollment using a random number generator), subjects will walk normally 
(session A) and be exposed to continuous side-to-side motions of the virtual hallway (Session B). These 
walking trials will last up to 20 min and will be separated by at least one week. 
 
3.2 
Study Duration, Enrollment and Number of Subjects 
This study will last up to 36 months. Subject recruitment and data collection will take up to 24 
months. The remaining 12 months will focus on data analysis, data interpretation, and manuscript 
preparation. We will recruit up to 20 older adults to participate.  
 
3.3 
Study Population 
Inclusion Criteria: 
1. Subjects Age 65+ years 
2. Be able to walk without an assistive aid (i.e., walker, cane) 
3. Have the full capacity to provide informed consent 
Exclusion Criteria: 
1. Current lower extremity injury or fracture 
2. Taking medication that causes dizziness 
3. Have a leg prosthesis 
4. Prisoners 
5. Individuals lacking the capacity to provide informed consent 

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STUDY PROCEDURES (what will be done) 
Subjects will be comfortably fit with a safety harness and instructed on all safety procedures. Subjects 
will then walk at their preferred speed on a force-sensing treadmill for 5 min to acclimate to the 
equipment and allow their movement patterns to stabilize. 
 
Subjects will then complete a block protocol design with pre and post measurements separated by up 
to 20 min of normal treadmill walking (Session A) or in the presence of optical flow perturbations 
(Session B).  Pre and post measurements will include baseline measurements during normal walking 
and: 
 
1) Foot placement targeting task. Subjects will be exposed to a series of footprint targets 
intermittently projected onto the treadmill belt. Subjects will be asked to direct their feet to the 
target with their next step as accurately as possible.  
 
2) Auditory ‘Stroop’ task. While wearing headphones with a microphone, subjects will hear the words 
high and low in pitches that are either high or low and asked to verbally identify the pitch of those 
words as quickly as possible.  
 
Subject Completion/ Withdrawal procedures 
If subjects are unable to complete the protocol or suffer a musculoskeletal injury before or during the 
time period when they are involved in the study, they will be withdrawn from the study. 
 
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STUDY EVALUATIONS AND MEASUREMENTS (how measurements will be made)   
3D motion capture and an instrumented treadmill will record the position and orientation of body 
segments and joints and ground reaction forces. Using custom software, we will compute the mean 
and standard deviation of step width variability, postural sway variability, and margin of stability 
variability. The outcome measure from the foot placement targeting task will be foot placement 
accuracy. The outcome measures from the auditory Stroop task will be cognitive-motor interference 
accuracy and response time. Efficacy measurements will be made using the change in each outcome 
measure after walking normally or with optical flow perturbations.  
 
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STATISTICAL CONSIDERATION    
Sample size is based on our published estimates of age-related differences in balance outcome 
measures. n=14 subjects per group would have 90% power to detect (p<0.05) a difference in dynamic 
instability during visually perturbed walking between healthy older (1.38 ± 0.20, unitless) and healthy 
young (1.20 ± 0.10, unitless) adults (Franz et al., 2015). This number of subjects would also sufficiently 
power our detecting differences in step width variability (8.92 ± 1.00 vs. 4.02 ± 0.96) (Francis et al., 
2015).  
 
 

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6.1 
Statistical Methods 
A two-way rmANOVA will test for significant main effects and interactions between time (Pre versus 
Post) and experimental session (perturbations versus normal walking). Significance will be defined for 
each main effect using an alpha level of 0.05. 
 
6.2 
Interim Analysis 
Given the non-invasive nature of the experiment and the relative risk involved, there are no criteria that 
will be used to stop the entire study prematurely.  
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STUDY INTERVENTION (drug, device or other intervention details) 
This study uses a custom virtual reality environment described in detail elsewhere (Franz et al., 2015), 
which consists of a virtual hallway that is speed-matched to a treadmill positioned inside the projection 
screen (Fig. 1). To the speed-matched virtual hallway, we add continuous mediolateral oscillations of 
optical flow which are prescribed as the sum of three sine waves (phase, φ = 0), such that a full 0.35 m 
amplitude is applied at 0.250 Hz and half that amplitude is applied at 0.125 Hz and 0.442 Hz. 
 
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SAFETY MANAGEMENT 
If a subject needs immediate medical assistance, we will call “911” for emergency services. Should a 
subject need non-urgent medical or psychological follow-up, research members will contact UNC Health 
Care to provide referrals. 
 
At least one research staff member will be monitoring the subjects' movement patterns during the data 
collection. If the subject experiences any discomfort, the data collection will be stopped immediately. 
 
If any member of the research team encounters unanticipated problems (including by not limited to 
adverse events), we will make necessary adjustments to the protocol and, where appropriate, report 
these events to IRB personnel. Our goal with protocol adjustments will be to further lessen the likelihood 
of unanticipated problems. 
 
If subjects are unable to complete the protocol or suffer a musculoskeletal injury before or during the 
time period when they are involved in the study, they will be withdrawn from the study. 
 
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DATA COLLECTION AND MANAGMENT  
We will minimize the breach of confidentiality as follows. All research will be conducted with only 
members of the research team present. The collection of information about subjects will be limited to the 
amount necessary to achieve the aims of the research. We are not utilizing computer-generated 
questionnaires. All data will be coded with unique subject identification numbers except consent forms 
(which are directly identifiable). Only members of the core research team will have access to the list that 
pairs subject names with numbers. This list will be kept separately from electronic data on password 
protected hard drives connected to a secure network and managed by Dr. Jason Franz. Subject data 
folders will be maintained in a secure filing cabinet where only the core research team has access. This 

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filing cabinet is located in the Applied Biomechanics Laboratory. Electronic data will be stored on 
computers managed via a secure School of Medicine network with password access. 
 
 
 
  
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RECRUITMENT STRATEGY 
All subjects will be primarily identified in person by communicating with UNC students and using flyers 
posted around the UNC campus and Chapel Hill community, after receiving approval to do so. Older 
adults will be further identified in person or by using flyers posted at local retirement communities and 
senior centers after receiving approval to do so. 
 
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CONSENT PROCESS 
Only persons with a prior knowledge of the research will be approached and identified in person. This 
may include, for example, an informational gathering at retirement community. This interaction will be 
limited to information contained in the email template and recruitment flyer, or to information needed 
to address any questions asked about the research by persons in attendance. 
 
Subjects recruited using the flyer or email template will contact a member of the research team by 
phone or email if interested in being recruited to participate. Once preliminary communication has 
been established, subjects will be invited to complete the telephone screening to assess basic eligibility 
criteria. If the subjects email or leave a phone message with their contact information, the study team 
will return the message to implement the telephone script. 
 
We will emphasize to prospective subjects that participation in this study is voluntary, and any 
discussions during the recruitment process will be strictly confidential. Our phone screening script 
further informs the subject that, if they do not qualify or choose not to complete the written informed 
consent, the phone screening data will be destroyed. 
 
We will not exclude potential subjects based on race, sex, gender, or ethnicity and thus we will ensure 
equal access to participation including women and minorities. 
 
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PLANS FOR PUBLICATION 
The publication policy will be based on the relative scientific contributions of each investigator and 
other key personnel. 
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REFERENCES