A Momentum-enabled Treadling Methodology to Improve Gait and Enhance Mobility in Patients With Peripheral Arterial Disease
Phase: NA
Conditions: Peripheral Arterial Disease
Sponsor: University of North Carolina, Chapel Hill

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PROTOCOL DOCUMENT 
 
 
Complete Title: Momentum-enabled Treadling Methodology to Improve Gait and Enhance Mobility 
 
Short Title: Treadling Intervention Study 
FDA IND/IDE (if applicable): Not Applicable.  
Sponsor: Treadwell Corporation via Subaward (National Institutes of Health) 
Protocol Date: November 26, 2018 
NCT Number: NCT03891641 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Principal Investigator (Jason R. Franz) 
10206C Mary Ellen Jones Building 
Chapel Hill, NC 27514 
Phone 919-966-6119 
email: jrfranz@email.unc.edu 
 
PROTOCOL TITLE:  
Momentum-enabled Treadling Methodology to Improve Gait and Enhance Mobility 
Short Title:  
Treadling Intervention Study  
Lead Investigator: 
Jason R. Franz, Ph.D. 
 University of North Carolina at Chapel Hill 
Version Date: November 26, 2018 
 
I confirm that I have read this protocol and understand it.    
Principal Investigator Name:  
 
 
Jason R. Franz  
 
 
 
Principal Investigator Signature:  
 
 
 
 
 
 
 
Date:   
 
 
 
 
 
November 2018 
 
 
 
 
 
 
 
 
 
 
 
 

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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 
Momentum-enabled Treadling Methodology to Improve Gait and 
Enhance Mobility 
Funder 
Treadwell Corporation via Subaward (National Institutes of Health) 
Clinical Phase 
Pilot 
Study Rationale 
Mobility impairment is a significant concern for the over 617 million 
people aged over 65 worldwide, with 17%, 28% and 47% of people aged 
65-74, 75-84, and 85+ years respectively reporting that difficulty walking 
interferes with their daily activities. While there is a heterogeneous 
mixture of causes for mobility loss in older adults, peripheral arterial 
disease (PAD) is a significant concern. PAD is predominately a disease of 
the elderly, affecting 20 – 30%adults aged over 65 years old with 
prevalence increasing with age. 
Elderly individuals with PAD experience significant mobility impairment, 
including lower walking speed, reduced walking distance, and lower 
physical activity levels, often caused by pain associated with intermittent 
claudication (IC), which leads to reduced independence and decreased 
quality of life. Furthermore, older adults with PAD experience 73% more 
falls than healthy counterparts and a greater prevalence of stumbling and 
unsteadiness, likely due to luminal narrowing of the lower extremity 
arteries, which results in impaired perfusion of skeletal muscles and 
worsening motor skills. 
There is a significant need for treatments that improve mobility in elderly 
individuals with PAD. Current therapies attempt this in a variety of ways. 
Rigorous exercise is the gold standard to improve mobility, pain-free 
walking time, and independence and may delay disease progression in 
patients with PAD. However, pain significantly complicates this 
treatment. Pain occurs on exertion, only diminishes with rest, and returns 
upon re-exertion, which limits exercise in 35 – 50% of PAD patients. As a 
result, patients fail to comply with prescribed exercises, likely explaining 
why studies exploring at-home exercise have mixed results for 
demonstration of efficacy. 
Accelerating progress to and improving compliance with rigorous 
exercise treatment has the potential to substantially improve patient 
mobility and independence. In this proposal, Treadwell will explore the 
ability of a novel treadling methodology, facilitated by the company’s 
innovative device (the TREDLRTM) to improve exercise tolerance and 
mobility in patients with PAD. Treadling improves lower extremity 
hemodynamics by activating the calf pump muscle, targeting the 
plantarflexors, which are the most affected area in PAD. These muscles 
are also critical for walking performance as they provide more than 50% 
of the mechanical power needed for walking. The plantarflexor muscles 
also generate 70%–80% of the mechanical power needed for forward 

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propulsion and swing initiation and are critical for modulating speed and 
step length in walking. For these reasons, we hypothesize treadling will 
improve plantarflexor-mediated mechanisms, leading to improved 
exercise tolerance and mobility in patients with PAD. In addition, the 
TREDLRTM is momentum-enabled; we hypothesize that this will result in 
less muscle engagement to activate the calf-pump mechanism, which 
may affect time to onset of pain. These collective hypotheses will be 
addressed in this research effort. 
Study Objective(s) 
The investigate the joint and muscle kinematic difference between 
treadling and conventional exercise, to explore improvements in mobility 
and exercise capacity in individuals who treadle compared to a control 
group, and to assess user affect and compliance with the device. 
Test Article(s) 
(If Applicable) 
The TREDLRTM involves an internal flywheel that generates momentum 
while the user initiates repetitive ankle flexion and extension 
movements. 
Study Design 
 
A randomized control design in which participants are randomly assigned 
to a 6-week treadling intervention or 6-weeks of usual physical activity. 
Subject Population 
key criteria for Inclusion 
and Exclusion: 
Inclusion Criteria 
1. Age: 65+ years 
2. Be able to walk without an assistive aid (i.e., walker, cane) 
3. Have the capacity the provide written informed consent 
4. Have previously diagnosed peripheral arterial disease (by self-
sport) (for PAD subjects) 
Exclusion Criteria 
1. Lower extremity injury or fracture within the last 6 months 
2. Have a leg prosthesis 
3. Prisoners 
4. Individuals clearly lacking the capacity to provide informed 
consent 
5. vestibular impairment 
 
Number of Subjects  
 
Up to 30 
Study Duration 
Subjects will participate in up to 20 total contacts, including 2 laboratory 
sessions (each lasting up to 3 hours) and, for those assigned to receive 
the treadling intervention, 3 sessions per week for 6 weeks). 
The entire study is expected to last three years, including time for study 
conduct and data analysis. 
Study Phases 
Screening 
Study Treatment 
Follow-Up   
 (1) Screening and baseline laboratory visit: 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 and complete Session 1 – a 
laboratory visit designed to establish baseline measures for all outcome 
measures. 

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(2) Training: Subjects that provide written informed consent and 
randomly assigned to receive the treadling intervention will complete 15-
min treadling sessions 3x/week for 6 weeks.  
(3) Follow-up: All subjects will complete Session 2 – a laboratory visit 
designed to test for changes in all outcome measures.  
Efficacy Evaluations 
Primary Outcome Measure(s): 
1. Change in Overground Walking Speed After Intervention [Time Frame: 
Baseline, 6 weeks] 
2. Change in 6-min Walk Distance [Time Frame: Baseline, 6 weeks] 
Secondary Outcome Measure(s): 
3. Change in Stride Length [Time Frame: Baseline, 6 weeks] 
4. Change in Peak Ankle Power [Time Frame: Baseline, 6 weeks] 
Statistical Analysis Plan 
A mixed factorial will test for main effects of and interactions between 
group assignment (treadling, controls) and time (pre, post) on primary 
and secondary outcomes. 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 
subaward 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 and throughout the intervention. If the subject 
experiences any discomfort, the data collection and/or the intervention 
itself 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 
Mobility impairment is a significant concern for the over 617 million people aged over 65 worldwide, with 17%, 
28% and 47% of people aged 65-74, 75-84, and 85+ years respectively reporting that difficulty walking interferes 
with their daily activities. While there is a heterogeneous mixture of causes for mobility loss in older adults, 
peripheral arterial disease (PAD) is a significant concern. PAD is predominately a disease of the elderly, affecting 
20 – 30%adults aged over 65 years old with prevalence increasing with age. 
Elderly individuals with PAD experience significant mobility impairment, including lower walking speed, reduced 
walking distance, and lower physical activity levels, often caused by pain associated with intermittent 
claudication (IC), which leads to reduced independence and decreased quality of life. Furthermore, older adults 
with PAD experience 73% more falls than healthy counterparts and a greater prevalence of stumbling and 
unsteadiness, likely due to luminal narrowing of the lower extremity arteries, which results in impaired perfusion 
of skeletal muscles and worsening motor skills. 
There is a significant need for treatments that improve mobility in elderly individuals with PAD. Current therapies 
attempt this in a variety of ways. Rigorous exercise is the gold standard to improve mobility, pain-free walking 
time, and independence and may delay disease progression in patients with PAD. However, pain significantly 
complicates this treatment. Pain occurs on exertion, only diminishes with rest, and returns upon re-exertion, 
which limits exercise in 35 – 50% of PAD patients. As a result, patients fail to comply with prescribed exercises, 
likely explaining why studies exploring at-home exercise have mixed results for demonstration of efficacy. 
Accelerating progress to and improving compliance with rigorous exercise treatment has the potential to 
substantially improve patient mobility and independence. In this proposal, Treadwell will explore the ability of a 
novel treadling methodology, facilitated by the company’s innovative device (the TREDLRTM) to improve exercise 
tolerance and mobility in patients with PAD. Treadling improves lower extremity hemodynamics by activating the 
calf pump muscle, targeting the plantarflexors, which are the most affected area in PAD. These muscles are also 
critical for walking performance as they provide more than 50% of the mechanical power needed for walking. The 
plantarflexor muscles also generate 70%–80% of the mechanical power needed for forward propulsion and swing 
initiation and are critical for modulating speed and step length in walking. For these reasons, we hypothesize 
treadling will improve plantarflexor-mediated mechanisms, leading to improved exercise tolerance and mobility 
in patients with PAD. In addition, the TREDLRTM is momentum-enabled; we hypothesize that this will result in less 
muscle engagement to activate the calf-pump mechanism, which may affect time to onset of pain. These 
collective hypotheses will be addressed in this research effort. 
1.2 
Name and Description of Investigational Product or Intervention  
Treadwell Corporation’s technology is a patented treadling methodology facilitated by a prototype treadling 
device (US Patent 7,883,451). The device, the TREDLRTM (Fig. 1), is fabricated with an internal flywheel 
mechanism that facilitates the natural flexion and 
extension movements of the ankles by lifting the 
forefoot to assist the anterior compartment muscles, 
allowing minimal exertion from the user. As a result, 
treadling is user-initiated, non-jarring, non-fatiguing, 
and improves blood flow in the lower extremities. 
 
 
 
Fig. 1: The TREDLRTM 
The TREDLRTM device (A) and demonstration of use (B). 

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1.3 
Relevant Literature and Data 
An early version of the TREDLRTM demonstrated safety and ability to increase blood flow in the lower limbs in 
two independent studies. Hope et al[1] (2011) measured arterial and venous flow velocities with ultrasound and 
demonstrated significant increases in both arterial and venous flow velocities during treadling in comparison to 
resting and cool down periods (p< 0.001) while heart rate, blood pressure, respiratory rate, and body 
temperature remained constant. Maximum velocity in the femoral vein (FV) increased on average from 0.1 to 
0.285 m/s (~3 fold), and minimum velocity in the FV increased on average from 0.01 to 0.07 m/s within 2 
minutes of the start of treadling[1]. Hemodynamic changes also occurred in the superficial femoral artery (SFA). 
Mean end-diastolic velocity (EDV) in the SFA rose from a resting velocity of 0.01 m/s to a mean average treadling 
velocity of 0.165 m/s (1580%), and mean peak systolic velocity (PSV) values in the SFA increased from a resting 
value of 0.75 to 1 m/s (33%).  
Hope et al. (2011) replicated earlier studies conducted by Currie et al (2010)[2], who also showed that blood flow 
velocity changes induced by treadling are comparable to exercise without being fatiguing or increasing vitals 
with dynamic peripheral vascular sonography to assess hemodynamic changes during lower limb movement. All 
studies were conducted with subjects that displayed a variety of negative health symptoms (e.g. coronary artery 
disease, hypertension, PAD, and diabetics) with no reports of adverse events, indicating that the TREDLRTM is 
safe to use with a broad range of cardiovascular and metabolic diseases. 
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STUDY OBJECTIVE  
This is a pilot study of a new exercise device (TREDLR) designed to facilitate repetitive ankle flexion/extension 
movements (i.e., "treadling") through a momentum-driven internal flywheel while seated. The specific goals of 
this project are to understand the joint and muscle kinematic difference between treadling and conventional 
exercise, to explore improvements in mobility and exercise capacity in individuals who treadle compared to a 
control group. 
 
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INVESTIGATIONAL PLAN (brief overview) 
 
3.1 
Study Design 
Subjects will be randomized into a treadling group (n=15) or a control group (n=15). Treadling subjects will do so 
3x per week (15 min sessions) for 6 weeks. The control group will be instructed to continue their normal daily 
activities. Pre-Post measurements will include walking performance, leg joint biomechanics (i.e., angles, 
moments, powers), and calf muscle contractile behavior via ultrasound. 
 
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 30 older adults to participate 
 
3.3 
Study Population 
Inclusion Criteria: 
1. Age: 65+ years 
2. Be able to walk without an assistive aid (i.e., walker, cane) 
3. Have the capacity the provide written informed consent 
4. Have previously diagnosed peripheral arterial disease (by self-sport) (for PAD subjects) 
 

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Exclusion Criteria: 
1. Lower extremity injury or fracture within the last 6 months 
2. Have a leg prosthesis 
3. Prisoners 
4. Individuals clearly lacking the capacity to provide informed consent 
5. vestibular impairment 
 
4 
STUDY PROCEDURES (what will be done) 
Screening: We will use an initial telephone screening (attached) to evaluate basic study eligibility. We will not 
retain phone screening data for subjects that do not qualify for the study or for subjects that do not provide 
written informed consent. In these cases, we will destroy telephone screening data. Subjects that meet 
inclusion/exclusion criteria following phone screening will be invited to participate in the remainder of the study. 
Prospective subjects who provide written informed consent during their initial visit will then complete a more 
detailed health questionnaire (attached). 
Study Activities Schedule: All subjects will complete an initial session lasting up to 3 hours to collect baseline 
biomechanics data. Subjects will then be randomly assigned to a treadling group (n=15) or a control group (n=15). 
Those subjects assigned to the treadling group will treadle 3x per week (15 min sessions) for a total of 6 weeks. 
Control subjects will be instructed to continue their usual daily activities. Finally, all subjects will complete a final 
session lasting up to 3 hours, identical in nature to the baseline session. 
Location: Applied Biomechanics Laboratory, University of North Carolina, Chapel Hill, NC. 
Subjects will be invited to complete written informed consent, a health questionnaire, and the experimental 
procedures outlined below. 
TREDLR Device: This study makes use of a device called the TREDLR, made by Treadwell Corporation. The device 
is completely unpowered, and is essentially a simple footstool that allows the feet to rotate back and forth (like 
tapping your toes). This rotation is subtle (i.e., well within the ankle's range of motion) and is facilitated by a small 
flywheel that helps the user to "drive" these rotations more easily. 
Baseline and Follow-Up Study Measurements: We will record the following subject characteristics: 
inclusion/exclusion criteria, birth date, height, weight, and typical weekly exercise. The following measures will 
be collected during walking, cycling, and treadling trials described below: forces between subjects' feet and 
ground (measured using force-plates), the motion of subjects' torso, pelvis, and legs (measure using 3D motion 
capture), leg muscle activity patterns (measured using electromyography).  
Baseline and Follow Up Study Procedures: Subjects will first visit the Applied Biomechanics Laboratory to 
participate in the consenting process and, for those who are eligible and agree to participate, a baseline session 
that will take up to 3 hours. Subjects will first walk 30 ft three times at their self-selected preferred walking 
speed. Subjects will walk at their preferred speed on a force-sensing treadmill for 5 min. During treadmill walking, 
subjects will be comfortably fit with a safety harness and instructed on all safety procedures.  
To conclude these sessions, subjects will perform a 6 min walk test, attempting to walk as far as they safely can in 
6 min. Finally, subjects will be randomly assigned to the treadling group or the control group. The treadling group 
will be instructed on the use of the TREDLR for subsequent training. 

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Within-Training Study Measurements: The following measures will be collected during each session of the 
training period from the TREDLR devices: session begin and end times and number of cycles per session. 
Within-Training Study Procedures:  We will make devices accessible to study participants to facilitate their 
regular use during supervised training sessions, which involves use of the TREDLR 3x per week for 15 min each. 
 
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 
overground walking speed, 6-min walk distance, stride length, and peak ankle power. Efficacy measurements 
will be made using the change in each outcome measure following the 6-week treadling intervention or control 
period. 
 
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STATISTICAL CONSIDERATION    
Using a conservative 80% power and an alpha level of 0.05, n = 10 subjects are required to resolve a minimal 
detectable change of 58.21 meters in 6-min walk distance (m) [3, 4]. For walking speed (m/s), the minimal 
detectable change is 0.108 m/s (80% power, alpha = 0.5, with n = 13 subjects), which would be considered 
clinically meaningful[5]. The ability to resolve these changes justifies the size selected for our intervention and 
control cohorts.   
 
6.1 
Statistical Methods 
 
A mixed factorial will test for main effects of and interactions between group assignment (treadling, controls) 
and time (pre, post) on primary and secondary outcomes. Significance will be defined 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) 
Treadwell Corporation’s technology is a patented treadling methodology facilitated by a prototype treadling 
device (US Patent 7,883,451). The device, the TREDLRTM (Fig. 1), is fabricated with an internal flywheel 
mechanism that facilitates the natural flexion and extension movements of the ankles by lifting the forefoot to 
assist the anterior compartment muscles, allowing minimal exertion from the user. Subjects randomly assigned 
to the treadling group will use the device 3x per week for 15 min each for a total of 6 weeks. 
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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. 

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At least one research staff member will be monitoring the subjects' movement patterns during the data collection 
and training sessoins. 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 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 
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. Chapel Hill is a popular community for people following 
retirement and has a high density of retirement communities and senior centers. Thus, there is a very high 
likelihood of having access to the projected number of subjects. 
 
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CONSENT PROCESS 
All study procedures will be described to the subjects prior to their visit to the lab and prior to obtaining consent. 
This includes a phone screening in which subjects will be described the details of the study purpose and 
procedures. All subjects will have ample opportunities to ask questions regarding the protocol prior to signing the 
consent. In addition, no member of the research team will recruit or consent any student from a class over which 
they preside. 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  
1. 
Hope, W.W., et al., Dynamic ultrasound and treadling: novel approaches to assess and improve lower 
extremity circulation. Am Surg, 2011. 77(8): p. 1091-3. 
2. 
Currie, L. and J. Hundley, Dynamic Peripheral Vascular Sonography: A Novel Technique. J Diagnostic 
Med Sonogr, 2010. 26: p. 130–136. 
3. 
Perera, S., et al., Meaningful change and responsiveness in common physical performance measures in 
older adults. J Am Geriatr Soc, 2006. 54(5): p. 743-9. 
4. 
McDermott, M.M. and T.S. Polonsky, Home-Based Exercise: A Therapeutic Option for Peripheral 
Artery Disease. Circulation, 2016. 134(16): p. 1127-1129. 
5. 
Goldberg, A. and S. Schepens, Measurement error and minimum detectable change in 4-meter gait 
speed in older adults. Aging Clin Exp Res, 2011. 23(5-6): p. 406-12.