Improving Physical Activity and Gait Symmetry After Total Knee Arthroplasty
Phase: NA
Conditions: Knee Replacement, Total, Knee Arthroplasty, Total
Sponsor: University of North Carolina, Chapel Hill

 
 
Improving Physical Activity and Gait Symmetry After Total Knee Arthroplasty 
Protocol 
 
 
NCT number NCT04090125 
Document Date 10/06/2022 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Activity and Gait Symmetry: Randomized Trial of an Intervention for Patients Following  
Total Knee Arthroplasty 
 
Protocol Number: 19-0568 
 
NCT Number: 04090125 
 
Principal Investigator: Kelli D. Allen, PhD 
 
Sponsor: University of North Carolina at Chapel Hill 
 
Grant Title: Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
 
Grant Number: R21-AR074149 
 
Funded by: 
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 
 
Version Number: 11.0 
 
6 October 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
ii 
Protocol v11.0 - 20221006 
   
 
 
Summary of Changes from Previous Version: 
 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
1.1, 1.2, 4.1, 9.1, 
9.2 and 9.4 
Change made to reduce the sample 
size from 72 to 60 for the study  
Sample size reduced due to 
challenges with enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
iii 
Protocol v11.0 - 20221006 
   
Table of Contents 
 
 
STATEMENT OF COMPLIANCE.………………………………………………………..………….....1 
INVESTIGATOR’S SIGNATURE…………………………………………………………………..……2 
1  
PROTOCOL SUMMARY…………………………………………………………………………... 3 
1.1 
Synopsis………………………………………………………………………………………3 
1.2 
Schema………………………………………………………………………………………. 6 
1.3 
Schedule of Activities………………………………………………………………………..7 
2 
 INTRODUCTION… .............................................................................................................. 8 
 2.1 
Study Rationale and Background…………………………………………………………. 8 
  2.1.1  Clinical Signficance ..................................................................................................... 8 
  2.1.2  Premise………………………………………………………………………………………. 8 
  2.1.3  Prior Studies and Rationale for Development…………………………………………….9 
 2.2 
Risk/Benefit Assessment…………………………………………………………………. 10 
  2.2.1  Known Potential Risks……………………………………………………………………..10 
  2.2.2 Known Potential Benefits…………………………………………………………………. 10 
  2.2.3 Assessment of Potential Risks and Benefits 
3 
STUDY OBJECTIVES AND ENDPOINTS .......................................................................... 11 
4 
STUDY DESIGN………………………………………………………………………………… .. 13 
 4.1  
Overall Design………………………………………………………………………………13 
 4.2  
Scientific Rationale for Study Design ........................................................................ 14 
 4.3   
Justification for Intervention ...................................................................................... 14 
 4.4  
End-of-Study Definition ............................................................................................. 14 
5 
STUDY POPULATION…………………………………………………………………………….15 
 5.1  
Inclusion Criteria ....................................................................................................... 15 
 5.2  
Exclusion Criteria ...................................................................................................... 15 
 5.3  
Lifestyle Considerations ............................................................................................ 15 
 5.4  
Screen Failures……………………………………………………………………………..15 
 5.5  
Strategies for Recruitment and Retention………………………………………………. 15 
6 
STUDY INTERVENTIONS 
 6.1  
Study Intervention Administration ............................................................................. 16 
 6.2  
Fidelity ....................................................................................................................... 18 
6.3  
Measures to Minimize Bias: Randomizaiton and Blinding……………………………..18 
6.4  
Study Intervention Adherence……………………………………………………………. 18 
6.5  
Concomitant Therapy………………………………………………………………………18 
7 
STUDY INTERVENTION DISCONTINUATION AND  
 
PARTICIPANT DISCONTINUATION/WITHDRAWAL……………………………………… ... 19 
 7.1   
Discontinuation of Study Intervention…………………………………………………… 19 
 7.2   
Participant Discontinuation/Withdrawal from the Study……………………………… . 19 
 7.3   
Lost to Follow-up………………………………………………………………………… .. 19 
8 
STUDY ASSESSMENTS AND PROCEDURES……………………………………………… . 20 
 8.1  
Endpoint and Other Non-Safety Assessments………………………………………… 20 
 8.2  
Safety Assessments……………………………………………………………………… 22 
 8.3  
Adverse Events and Serious Adverse Events………………………………………… . 22 
8.3.1  Definition of Adverse Events……………………………………………………………. .22 
8.3.2  Definition of Serious Adverse Events………………………………………………….. . 22 
8.3.3  Classification of an Adverse Event……………………………………………………. ... 22 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
iv 
Protocol v11.0 - 20221006 
   
8.3.4  Time Period and Frequence for Event Assessment and Follow-up…………………..23 
8.3.5  Adverse Event Reporting………………………………………………………………. ... 24 
8.3.6  Serious Adverse Event Reporting……………………………………………………… . 24 
8.3.7  Reporting Events to Participants……………………………………………………….. . 24 
8.3.8  Events of Special Interest……………………………………………………………….. . 24 
8.3.9  Reporting of Pregnancy………………………………………………………………….. 24 
 8.4  
 Unanticipated Problems………………………………………………………………… ..24 
8.4.1  Definition of Unanticipated Problems…………………………………………………….24 
8.4.2  Unanticipated Problems Reporting……………………………………………………… 24 
8.4.3  Reporting Unanticipated Problems to Participants……………………………………. 24 
9 
STATISTICAL CONSIDERATIONS ...……………………………………………………….. .. .25 
9.1   
Statistical Hypotheses…………………………………………………………………… . 25 
9.2   
Sample Size Determination……………………………………………………………… 26 
9.3  
Populations for Analyses…………………………………………………………………. 26 
9.4  
Statistical Analyses……………………………………………………………………… .. 26 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............... 28 
 10.1 Regulatory, Ethical, and Study Oversight Considerations…………………………………. 28 
10.1.1  Informed Consent Process……………………………………………………………….. 28 
10.1.2  Study Discontinuation and Closure……………………………………………………… 28 
10.1.3  Confidentiality and Privacy………………………………………………………………. 29 
10.1.4  Future Use of Stored Specimens and Data……………………………………………. 30 
10.1.5  Key Roles and Study Governance………………………………………………………. 30 
10.1.6  Safety Oversight…………………………………………………………………………… 31 
10.1.7  Clinical Monitoring………………………………………………………………………… 31 
10.1.8  Quality Assurance and Quality Control…………………………………………………..31 
10.1.9  Data Handling and Record Keeping…………………………………………………….. 32 
10.1.10 Protocol Deviations………………………………………………………………………. 32 
10.1.11 Publication and Data Sharing Policy…………………………………………………… 32 
10.1.12 Conflict of Interest Policy………………………………………………………………… 33 
 10.2 
Additional Considerations………………………………………………………………… 33 
 10.3 
Abbreviations and Special Terms……………………………………………………… .. 34 
 10.4 
Protocol Amendment History……………………………………………………………. . 35 
11  
References………………………………………………………………………………………37 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
1 
Protocol v11.0 - 20221006  
 
 
 
STATEMENT OF COMPLIANCE 
 
 
The trial will be carried out in accordance with International Council on Harmonisation Good Clinical 
Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 
46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible for 
the conduct, management, or oversight of NIH-funded clinical trials have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the Institutional Review Board (IRB) for review and approval. Approval of both the protocol 
and the consent form(s) must be obtained before any participant is consented. Any amendment to the 
protocol will require review and approval by the IRB before the changes are implemented to the study. 
All changes to the consent form(s) will be IRB approved; a determination will be made regarding whether 
a new consent needs to be obtained from participants who provided consent, using a previously approved 
consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
2 
Protocol v11.0 - 20221006  
 
 
INVESTIGATOR’S SIGNATURE 
 
The signature below constitutes the approval of this protocol and provides the necessary assurances that this 
study will be conducted according to all stipulations of the protocol, including all statements regarding 
confidentiality, and according to local legal and regulatory requirements and applicable US federal regulations 
and ICH guidelines. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
 
 
Name:  
 
Title: 
 
 
 
 
Investigator Contact Information 
Affiliation: University of North Carolina at Chapel Hill 
Address: 3300 Thurston Bldg., CB #7280, Chapel Hill, NC  27599-7280 
Telephone:919-966-0558 
Email: kdallen@med.unc.edu 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
3 
Protocol v11.0 - 20221006  
 
 
1 
PROTOCOL SUMMARY 
 
 
1.1 
SYNOPSIS 
 
 
Title: 
Improving Physical Activity and Gait Symmetry after Total Knee 
Arthroplasty 
Grant Number: 
R21-AR074149 
Study Description: 
The overall objective of this study is to gather preliminary evidence 
on the efficacy, feasibility and acceptability of the Physical Activity 
and Symmetry (PAS) intervention.  Specific hypotheses are as 
follows: 
 
H1:   The PAS group will have greater improvement in objectively 
assessed physical activity (PA) at the 3-month and 6-month 
assessments, compared to the attention control (ATT) group. The 
main co-primary metric of interest is minutes of moderate to 
vigorous physical activity; other secondary metrics will include step 
count, minutes of any PA, and sedentary minutes.    
 
H2: The post-total knee arthroplasty (TKA) exercise group will have 
greater improvement in peak load symmetry during walking at the 
3-month and 6-month assessments, compared to the ATT group. 
 
Objectives*: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Specific Aim 1:  Obtain preliminary data on the efficacy of the PAS 
program with respect to the change in objectively assessed physical 
activity, measured via accelerometers. 
Specific Aim 2:  Obtain preliminary data on the efficacy of the PAS 
program with respect to change in peak load symmetry during 
walking, measured by a novel 3-sensor insole device. 
Specific Aim 3: Assess the feasibility and acceptability of the PAS 
program following TKA. 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
4 
Protocol v11.0 - 20221006  
Endpoints*: 
Primary Endpoints: 
One co-primary primary end- point / outcome is objectively 
assessed PA, measured via accelerometer.  The primary metric of 
interest is minutes of moderate to vigorous physical activity 
(MVPA). This will be assessed at both 3-month and 6-month follow-
up time points.   
 
The other co-primary primary end- point / outcome is peak load 
symmetry during gait.   This will be assessed at both 3-month and 
6-month follow-up time points.   
 
Secondary Endpoints: 
In addition to minutes of MVPA, secondary metrics of physical 
activity will include step count, minutes of any PA, and sedentary 
minutes. In addition to peak load symmetry during gait, peak load 
symmetry will be assessed during physical performance tests 
including the 30-second stair stand test, 40m fast-paced walk, stair 
climb test, and Timed Up and Go (TUG) test. 
 
Feasibility metrics include recruitment, retention, intervention 
delivery, and outcome assessment. Perceptions of acceptability will 
be obtained from patients and physical therapists using open-ended 
questions. 
 
Exploratory outcomes include self-reported PA, physical 
performance tests, balance, knee symptoms, and kinesiophobia. 
 
 
Study Population: 
 
N = 60 participants receiving post-TKA physical therapy (PT) at a 
University of North Carolina (UNC) Healthcare System or at 
physical therapy clinics outside of UNC. We will enroll both males 
and females, 18 years of age and older from all racial and ethnic 
backgrounds.   
 
Phase* or Stage: 
Based on the Obesity-Related Behavioral Intervention Trials 
(ORBIT) framework, this study is a Phase II Preliminary Testing 
trial. 
 
Description of 
Sites/Facilities Enrolling 
Participants: 
We will only be enrolling patients receiving post-TKA PT at a UNC 
Healthcare System clinic or at physical therapy clinics outside of 
UNC. 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
5 
Protocol v11.0 - 20221006  
Description of Study 
Intervention/Experimental 
Manipulation: 
The PAS program significantly augments usual post-TKA PT, 
specifically addressing critical gaps of physical inactivity and joint 
loading asymmetry. The PAS program will be initiated during the 
final usual care PT visits, allowing integration and capitalizing on 
the existing patient-provider relationship. PAS content will be 
included within the last two routine PT visits (Session 1 and 2, see 
Table 1, Section 6.1 Study Intervention Administration). Then, PAS 
participants will receive a follow-up call after 4 weeks (to assist with 
activity progression and problem-solving) and an additional visit 
after 8 weeks (conducted in-person if possible or remotely via an 
IRB approved video platform or by phone). 
Study Duration*: 
18 months 
Participant Duration: 
6 months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
6 
Protocol v11.0 - 20221006  
 
1.2 
SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
7 
Protocol v11.0 - 20221006  
1.3 
SCHEDULE OF ACTIVITIES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
8 
Protocol v11.0 - 20221006  
2 
INTRODUCTION 
 
2.1 
STUDY RATIONALE AND BACKGROUND 
 
 
2.1.1. CLINICAL SIGNIFICANCE  
 
TKA Rates are High and Increasing Rapidly. TKA is the most common surgical procedure involving a hospital 
stay in the United States. In 2012, TKAs accounted for >700,000 hospital stays, and rates increased 66% from 
2003-2012 1. Demand for TKA is expected to rise to 3.48 million procedures by 2030 2. About 40% of patients 
with unilateral TKA will progress to a TKA on the contralateral side within 10 years 3,4. As a result of the high 
surgical volume and the progression of disease in the contralateral limb, it is imperative that post-TKA 
outcomes are optimized through effective rehabilitation strategies.    
There are Critical Deficits in Post-TKA Outcomes. Studies have identified two key deficits in individuals’ 
activity-related trajectories following TKA. First, despite major improvements in joint pain for most patients, 
overall PA levels remain very low 5,6. Although some studies suggest that patients perceive they are more 
active after surgery than before, accelerometer-based studies demonstrate that PA levels do not increase 
meaningfully following TKA, remaining well below Department of Health and Human Services (DHHS) 
guidelines7 as well as PA levels of healthy individuals 5,8-14. For example, participants in one study spent 8.1% 
of the day in movement-related activity prior to TKA, and this increased to only 9.1% 6 months following 
surgery 10. This has negative implications not only for function and joint health but also for managing common 
comorbid diseases and improving overall physical and psychological health. Increases in body weight are also 
common during the year following TKA 15,16, and increasing PA can help to mitigate this risk. The second post-
TKA deficit highlighted in recent studies involves joint loading asymmetries. Although patients show 
improvements in pain and some aspects of physical performance following TKA and outpatient rehabilitation 
17,18, many patients continue to demonstrate movement asymmetries that result in greater load on the non-
surgical limb 19. Importantly, this likely contributes to the increased risk for TKA on the contralateral limb within 
10 years of the primary TKA procedure 17. Research indicates that joint loading asymmetries are adopted as a 
result of pre-operative pain and weakness, and the compensatory movement mechanics persist following 
surgery despite resolution of pain and completion of traditional rehabilitation programs 20; this indicates the 
importance of a re-training process, in which patients learn to correct maladaptive movement patterns that 
perpetuate joint loading asymmetries.   
Gaps in the Post-TKA Rehabilitation Process. Although outpatient PT is a standard practice following TKA, 
there is very little guidance regarding the most appropriate post-TKA rehabilitation regimen 17,21, and, as a 
result, there is substantial variability in post-TKA PT 22-24.  Importantly, neither deficit described above – overall 
PA and joint loading asymmetry – is adequately addressed in current post-TKA rehabilitation paradigms 22,23. 
Specifically, studies show lack of attention to cardiovascular training (e.g. general aerobic activity), guidance in 
exercise progression, and balance interventions 22,23. This highlights the need to optimize the post-TKA 
rehabilitation process so that these key outcomes are adequately addressed.    
Goal and Importance of this Exploratory Trial. To address these critical gaps, we will conduct an exploratory 
trial of a novel PAS intervention that focuses on the persistent deficits of physical inactivity and joint loading 
asymmetry following TKA. Randomized pilot study methods will be used to test hypotheses related to PAS 
efficacy (Aims 1 and 2) and feasibility and acceptability (Aim 3). This exploratory study is required prior to a 
larger trial because:  1) Preliminary data on the PAS intervention are needed; although we hypothesize that it 
will result in meaningful improvements in PA and symmetry, if this is not confirmed then further investment in a 
large trial would not be warranted.  2) The PAS intervention will be integrated in real-world PT settings, and 
preliminary work is needed to establish logistical procedures.  
 
 
 
2.1.2. PREMISE 
 
The PAS intervention is based on previous studies of effective strategies for improving PA and joint loading 
symmetry in various patient populations. With regard to improving PA, the PAS intervention will utilize goal 
setting, brief motivational interviewing (MI) and connection of patients with community programs and other PA 

,PSURYLQJ3K\VLFDO$FWLYLW\DQG*DLW6\PPHWU\DIWHU7RWDO.QHH$UWKURSODVW\
9HUVLRQ
3URWRFRO

2FWREHU

3URWRFROY
UHVRXUFHV:LWKUHVSHFWWRPLWLJDWLQJORDGLQJDV\PPHWULHVWKH3$6LQWHUYHQWLRQZLOOHPSOR\EDODQFH
H[HUFLVHVIRUWZRUHDVRQV)LUVWVLQFHRIWKHJDLWF\FOHLVVSHQWLQVLQJOHOHJVWDQFHLQDELOLW\WREDODQFHRQ
RQHOHJLPSDFWVJDLWRXWFRPHVDVZHOODVJDLWVWDELOLW\6WXGLHVKDYHDGGHGEDODQFHH[HUFLVHVWRHDUO\SRVW
7.$UHKDELOLWDWLRQDQGVKRZQLPSURYHPHQWVLQPXOWLSOHRXWFRPHVEXWRXUWDUJHWRIMRLQWORDGLQJ
V\PPHWU\KDVQRWEHHQH[DPLQHG6HFRQGWHDFKLQJSDWLHQWVVSHFLILFJDLWUHWUDLQLQJVWUDWHJLHVWRDGGUHVV
ORDGLQJDV\PPHWULHVLVYHU\FKDOOHQJLQJLQUHVHDUFKVHWWLQJVDQGZRXOGEHHYHQPRUHGLIILFXOWZLWKDKRPH
H[HUFLVHSURJUDP6PDOOVWXGLHVKDYHXVHGELRIHHGEDFNVLPLODUWRRXUSURSRVHGVWUDWHJ\WRKHOSSDWLHQWV
OHDUQWRSODFHHTXDODPRXQWVRIIRUFHRQULJKWDQGOHIWOHJVDIWHU7.$UHVXOWLQJLQLPSURYHPHQWVLQNQHH
PRYHPHQWGXULQJJDLW+RZHYHUWKHVHVWXGLHVXVHGWHFKQRORJLHVWKDWDUHQRWSUDFWLFDOWRLPSOHPHQW
ZLGHO\LQFOLQLFDODQGKRPHVHWWLQJVRXUDSSURDFKDGGUHVVHVWKLVOLPLWDWLRQ
35,25678',(6$1'5$7,21$/()25'(9(/230(17
'U$OOHQOHDGSULQFLSDOLQYHVWLJDWRU>3,@LVDQH[HUFLVHVFLHQWLVWDQGKHDOWKVHUYLFHVUHVHDUFKHUZKRKDVOHG
HLJKWWULDOVRILQWHUYHQWLRQVIRUSDWLHQWVZLWKRVWHRDUWKULWLV2$'U4XHHQPXOWLSOH3,LVDELRPHFKDQLVW
ZKRKDVOHGORQJWHUPRXWFRPHVVWXGLHVLQDYDULHW\RIRUWKRSDHGLFSRSXODWLRQVDVZHOODVVWXGLHVDVVHVVLQJ
ORDGLQJDQGPRYHPHQWV\PPHWU\'U+LOOLVDSK\VLFDOWKHUDSLVWZKRVHFOLQLFDODQGUHVHDUFKLQWHUHVWV
IRFXVPXVFXORVNHOHWDOFRQGLWLRQV'U6FKZDUW]LVDELRVWDWLVWLFLDQZLWKH[SHUWLVHLQDQDO\VHVRIUDQGRPL]HG
WULDOV'U+DOHVLVDQH[SHUWLQWKHXVHRIDFFHOHURPHWHUVWRPHDVXUH3$
'UV$OOHQDQG4XHHQUHFHQWO\FROODERUDWHGRQDSLORWVWXG\RIIXQFWLRQDOPRYHPHQWUHWUDLQLQJIROORZLQJWRWDOKLS
DUWKURSODVW\LQ9HWHUDQV'HSDUWPHQWRI9HWHUDQV$IIDLUV,5;3DUWLFLSDQWVQ VKRZHG
LPSURYHPHQWVLQVLQJOHOHJVWDQFHWLPHIXQFWLRQDOWHVWVDQGVHOIUHSRUWHGKLSV\PSWRPV7KHLQWHUYHQWLRQ
LQFOXGHGHOHPHQWVVLPLODUWRWKH3$6SURJUDPLQFOXGLQJWDLORULQJRIH[HUFLVHVWRSDWLHQWV¶SURJUHVVLRQ2XU
H[SHULHQFHZLWKGHOLYHULQJWKLVLQWHUYHQWLRQDVZHOODVUHFUXLWLQJDQGUHWDLQLQJWKLVSRVWVXUJLFDOJURXS
IROORZXSFRPSOHWHGSURYLGHYDOXDEOHH[SHULHQFHIRUWKHSURSRVHGVWXG\
'UV$OOHQ+LOODQG6FKZDUW]FROODERUDWHGRQDUDQGRPL]HGWULDOFRPSDULQJ37ZLWKLQWHUQHWEDVHGH[HUFLVH
WUDLQLQJIRULQGLYLGXDOVZLWK2$2IKLJKUHOHYDQFHWRWKHSURSRVHGVWXG\IRXU37SUDFWLFHV81&DQG
VXUURXQGLQJFRPPXQLWLHVGHOLYHUHGWKHVWXG\LQWHUYHQWLRQWRSDUWLFLSDQWVWKLVLOOXVWUDWHVRXUDELOLW\WRHQJDJH
SK\VLFDOWKHUDSLVWVLQWKLVW\SHRIUHVHDUFKDQGDGGUHVVORJLVWLFDOLVVXHVUHODWHGWRLQWHJUDWLQJUHVHDUFKLQWR
FOLQLFDOSUDFWLFH7KLVVWXG\DOVRXVHGVLPLODUDQDO\WLFVWUDWHJLHVLQFOXGLQJPXOWLSOHLPSXWDWLRQ
'U4XHHQKDVSLORWWHVWHGQRYHOVHQVRULQVROHVORDGVRO
1RYHO(OHFWURQLFV6W3DXO01WKDWZLOOEHXVHGIRU
PHDVXULQJMRLQWORDGLQJV\PPHWU\7KLVKDVLQFOXGHG$
SDUWLFLSDQWVWXG\VKRZLQJWKDWWKHPD[LPXPIRUFH
JHQHUDWHGGXULQJZDONLQJZDVFRPSDUDEOHZKHQPHDVXUHG
E\ORDGVROLQVROHVDQGDQHPEHGGHGIRUFHSODWH,QWUDFODVV
&RUUHODWLRQ&RHIILFLHQW,&& ORDGVROLQVROHVDOVR
KDGH[FHOOHQWEHWZHHQGD\UHOLDELOLW\,&& $
VWXG\RIILYHSDWLHQWVZLWKNQHH2$GHPRQVWUDWLQJVLGHWR
VLGHDV\PPHWULHVPHDVXUHGZLWKWKHORDGVROGXULQJ
ZDONLQJDQGVWDLUFOLPELQJ2IKLJKUHOHYDQFHWRWKH
SURSRVHGVWXG\PHDVXUHPHQWRIMRLQWORDGLQJDV\PPHWULHV
GXULQJJDLWDPRQJSDWLHQWVIROORZLQJ7.$)LJXUHLVDQ
H[DPSOHRIDSDWLHQWZLWKMRLQWDV\PPHWU\SHUVLVWLQJILYH
\HDUVDIWHUDVXFFHVVIXOULJKW7.$
)LJXUH/RDGVRO0HDVXUHG-RLQW/RDG'XULQJ
*DLW<HDUVDIWHU5LJKW7.$
J
0
0.2
0.4
0.6
0.8
1
1.2
1.4
Left
Right
%RG\:HLJKW

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
10 
Protocol v11.0 - 20221006  
2.2 
RISK/BENEFIT ASSESSMENT 
 
2.2.1  KNOWN POTENTIAL RISKS 
 
Emotional distress: it is unlikely that the types of questions participants will be asked in this study will result 
in emotional distress, but we understand that participants may be uncomfortable with answering questions 
about some aspect of their health or other things about them. To minimize this risk, we will let participants 
know they may choose not to answer any study questions and can still be involved in the study. 
 
Breach of confidentiality: we will be collecting some elements of personal health information (PHI) necessary 
for the study. To minimize breaches of confidentiality, all data will be stored on a secure UNC server or a UNC 
IRB approved platform for sharing PHI (with Virginia Tech), and paper 
information will be stored in locked filing cabinets in the office of a study team member.  Only approved study 
personnel will have access to those data. 
 
Risks of Exercise: Injury associated with mild-to-moderate physical activity is rare or infrequent. Because 
participants will all be post TKA, mild-to-moderate PA may be associated with short-term increases in pain or 
discomfort; we estimate short-term likelihood to be "common." However, longer-term increases in pain or 
discomfort after this type of activity is "infrequent" when PA is done appropriately. To minimize all of these 
risks, we will ensure that participants are given instructions for safe and appropriate physical activity levels and 
techniques for individuals post TKA. Participants will be given information on how to manage activity-related 
pain or discomfort. They will also be instructed that if pain is still elevated two hours after PA, they should 
reduce the intensity level during the next activity session. 
 
2.2.2 KNOWN POTENTIAL BENEFITS 
 
Participants may experience improved physical function, decreased pain, increased PA and 
improved joint loading symmetry. It is possible that this study may not benefit participants directly, but 
participation in this study may lead to information that can benefit others receiving post-TKA PT. 
 
 
2.2.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
This is a minimal risk study with risks that are comparable to those that would be encountered during typical 
PT or exercise programs in clinical or community settings.  Functional tests also mirror activities conducted 
during normal daily routines (e.g., walking, chair stands).  Although muscle or joint soreness may occur 
following assessments or intervention sessions, all of the activities being conducted are necessary for the 
scientific rigor of the study.  In particular, the function tests being conducted are those recommended by the 
Osteoarthritis Research Society International (OARSI).  Section 8.2 on Safety Assessments describes the 
study team’s plans to minimize risks associated with intervention sessions and outcome assessment.  Given 
the high and increasing rate of TKAs, the persistent deficits of physical inactivity and joint loading asymmetry, 
and the lack of a standard, evidence-based approach to address these deficits in rehabilitation settings, we 
believe the value of the information to be gained outweighs the risks of participation in the study.  
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
11 
Protocol v11.0 - 20221006  
3  
STUDY OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary 
Obtain preliminary data 
on the efficacy of the 
PAS program with 
respect to the change in 
objectively assessed 
physical activity, 
measured via 
accelerometers. 
H1:   The PAS group will 
have greater improvement 
in objectively assessed 
physical activity at the 3-
month and 6-month 
assessments, compared to 
the ATT control group. The 
main co-primary metric of 
interest is MVPA.  
 
One co-primary primary end- 
point / outcome is objectively 
assessed PA, measured via 
accelerometer.   This will be 
assessed at both 3-month 
and 6-month follow-up time 
points.  The rationale for 
these time points is 
described in the Overall 
Design section, and the 
rationale for sample size and 
analysis including co-primary 
outcomes is described in the 
Statistical Considerations 
Section.   
This is a co-primary outcome because it 
addresses one of the key deficits being 
addressed in the PAS intervention:  physical 
inactivity.  MVPA was particularly chosen as 
the primary metric because it corresponds to 
DHHS PA recommendations.     
Obtain preliminary data 
on the efficacy of the 
PAS program with 
respect to change in 
peak load symmetry 
during walking, 
measured by a novel 3-
sensor insole device.  
H2: The post-TKA exercise 
group will have greater 
improvement in peak load 
symmetry during walking 
at the 3-month and 6-
month assessments, 
compared to the ATT 
control group. The main 
co-primary outcome of 
interest will be the peak 
load - limb symmetry index 
during level walking. 
The other co-primary primary 
end- point / outcome is peak 
load symmetry during 
walking.   This will be 
assessed at both 3-month 
and 6-month follow-up time 
points.  The rationale for 
these time points is 
described in the Overall 
Design section, and the 
rationale for sample size and 
analysis including co-primary 
outcomes is described in the 
Statistical Considerations 
Section.   
This is a co-primary outcome because it 
addresses one of the key deficits being 
addressed in the PAS intervention:  joint load 
asymmetry during gait.   
Secondary 
Obtain preliminary data 
on the efficacy of the 
PAS program with 
respect to the change in 
secondary metrics of 
objectively assessed PA, 
In addition to minutes of 
MVPA, secondary metrics 
will include step count, 
minutes of any PA, and 
sedentary minutes 
These secondary metrics will be assessed 
because they measure aspects of PA that are 
complementary to minutes of MVPA and also 
have clinical relevance.  

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
12 
Protocol v11.0 - 20221006  
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
measured via 
accelerometers 
Obtain preliminary data 
on the efficacy of the 
PAS program with 
respect to change in 
peak load symmetry 
during additional 
activities, measured by a 
novel 3-sensor insole 
device.  
 
 
In addition to peak load 
symmetry during gait, peak 
load symmetry will be 
assessed during physical 
performance tests including  
the 30-second stair stand 
test, 40m fast-paced walk, 
stair climb test, and TUG 
test. 
 
These secondary metrics of load symmetry 
are being included because they are 
complement the primary measure of load 
symmetry during gait.  The physical 
performance tests being assessed represent 
typical daily activities, in which it is important 
to understand patterns of joint loading.  
Assess the feasibility 
and acceptability of the 
PAS program following 
TKA. 
 
Feasibility metrics include 
recruitment, retention, 
intervention delivery, and 
outcome assessment. 
Perceptions of acceptability 
will be obtained from 
patients and physical 
therapists using open-ended 
questions.  
This information if important for planning for a 
future, larger trial and for refining the PAS 
intervention as needed.  
Tertiary / Exploratory  
Obtain preliminary data 
on the efficacy of the 
PAS program with 
respect to the change in 
exploratory outcomes 
relevant to post-TKA 
recovery.  
Exploratory outcomes 
include self-reported PA, 
physical performance tests, 
balance, knee symptoms, 
and kinesiophobia. 
These exploratory outcomes were chosen 
because they are recommended for trials 
involving knee OA and / or represent patient-
centered outcomes relevant to post-TKA 
recovery. 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
13 
Protocol v11.0 - 20221006  
4  
STUDY DESIGN 
 
4.1  
OVERALL DESIGN   
 
The overall objective of this study is to gather preliminary evidence on the efficacy, feasibility and acceptability 
of the PAS intervention.  Specific aims are: 
Specific Aim 1:  Obtain preliminary data on the efficacy of the PAS program with respect to the change 
in objectively assessed physical activity, measured via accelerometers. 
H1:   The PAS group will have greater improvement in objectively assessed PA at the 3-month and 6-month 
assessments, compared to the ATT control group. The main co-primary metric of interest is minutes of MVPA; 
other secondary metrics will include step count, minutes of any PA, and sedentary minutes.    
Specific Aim 2:  Obtain preliminary data on the efficacy of the PAS program with respect to change in 
peak load symmetry during walking, measured by a novel 3-sensor insole device.  
H2: The post-TKA exercise group will have greater improvement in peak load symmetry during walking at the 
3-month and 6-month assessments, compared to the ATT control group. The main co-primary outcome of 
interest will be the peak load - limb symmetry index during level walking; secondary outcomes will be peak load 
- limb symmetry index values during additional physical performance tasks.       
Specific Aim 3: Assess the feasibility and acceptability of the PAS program following TKA. 
3a. Measure feasibility metrics related to recruitment, retention, intervention delivery, and outcome 
assessment.  
3b. Assess perceptions of acceptability of the intervention from patients and physical therapists and refine the 
intervention based on this feedback.  
 
This will be an exploratory, single site randomized controlled trial with 60 patients equally allocated to the PAS 
intervention or an ATT control group (see Schema section above).  Based on the ORBIT framework (which has 
application beyond the topic area of obesity), this study is a Phase II Preliminary Testing trial. Randomization 
will be stratified according to gender and presence of self-reported pain (≥3 on a 10 point scale) in any lower 
extremity joint (hip, knee or ankle) in addition to the surgical knee, to ensure that the groups are balanced in 
these respects.  We chose patient-level randomization because it is a straight-forward design that avoids 
potential biases and challenges of cluster randomization, such as imbalances in participant characteristics 
across study arms and attrition of study physical therapists 41,42.  With this design, each study therapist can 
treat patients in both study arms.  Although the PAS program will involve discrete components that are distinct 
from usual post-TKA PT (which will be delivered to the ATT control group), we acknowledge the risk of 
contamination of intervention delivery. To mitigate this risk, we will employ an intensive fidelity monitoring 
process, described below and in the Intervention Documents. If we find in this exploratory study that 
contamination is a concern, clinic-level randomization will be considered for a larger trial. The typical length of 
post-TKA PT is about 12 weeks. We will enroll patients approximately 4 weeks from initiation of outpatient PT, 
allowing time for randomization and notification of the treating therapist to begin the PAS intervention before 
PT is complete. Follow-up assessments will be conducted 3 months after the beginning intervention visits 
(shortly following to the end of the PAS intervention) and after 6 months (sustainability end point).  Regarding 
the 3-month follow-up time point, we selected this interval because it will: 1) allow for several weeks for 
participants to act on content delivered in the 8-week intervention visit and 2) allow sufficient time for 
scheduling first follow-up assessments after all intervention visits have been complete.  Longer term outcomes 
will be included in a larger trial.  
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
14 
Protocol v11.0 - 20221006  
4.2   
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
The ATT control group was selected to account for potential effects of intervention-related contacts (e.g., 
“attention”) that are not specific to the PAS program components (e.g., the specific rehabilitation and exercise 
program being delivered in the PAS intervention). Additional comments regarding rationale for the study design 
are described in Section 4.1. 
 
4.3  
JUSTIFICATION FOR INTERVENTION 
 
The intervention is described in detail in Section 6.  The number, frequency and types of contacts were 
selected based on ability to deliver the PAS content, as well as feasibility of administration in real-world clinical 
settings. We chose for the first 2 PAS visits to be included within the context of routine post-TKA PT so that it 
would be integrated into routine care.  The 4-week and 8-week contacts were selected to include a reasonable, 
feasible amount of contact – beyond the typical post-TKA time period – to follow up with patients regarding 
their progress with components of the PAS intervention.  Because this intervention includes only 4 contacts, 
we have not defined a separate “minimum-acceptable” participation in the intervention.  Ideal participation 
includes participation in all visits.  As part of this exploratory trial, we will be monitoring the feasibility and rates 
of visit completion, in preparation for a larger trial. In this study, primary analyses will include all randomized 
participants, regardless of amount of intervention completion.  However, we may conduct additional exploratory 
analyses that account for different patterns of intervention completion.  
 
4.4  
END-OF-STUDY DEFINITION 
 
A participant is considered to have completed the study if he or she has completed 6-month follow-up 
assessment. As noted above, there is no minimum number of intervention visits required to meet at definition 
of “completion,” but patterns of intervention completion will be assessed.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
15 
Protocol v11.0 - 20221006  
5 
  
STUDY POPULATION  
 
5.1  
INCLUSION CRITERIA 
 
All participants must be receiving post-TKA PT from a physical therapist at a UNC Healthcare System clinic or 
at physical therapy clinics outside of UNC. We will include individuals with OA in other lower extremity joints to 
maximize generalizability and help inform the larger trial.   
 
5.2  
EXCLUSION CRITERIA 
 
Exclusion criteria are:  significant cognitive impairment, neurological disorders affecting gait, systemic 
rheumatic disease; hospitalization for a cardiovascular condition the past six months; psychosis; substance 
abuse disorder; lower extremity surgery in the past year; planning total joint replacement in next 6 months; any 
other health conditions determined to be contraindications to a home exercise program. 
 
5.3  
LIFESTYLE CONSIDERATIONS 
N/A 
 
5.4  
SCREEN FAILURES 
 
Screen failures are defined as participants who consent to participate in this study but are not subsequently 
assigned to the study intervention or entered in the study. Individuals who do not meet the criteria for 
participation in this trial (screen failure) because of meeting one or more exclusion criteria (e.g., development 
of an exclusionary health condition) will not be rescreened.  This is because of the brief period of time in which 
participants are eligible to participate in the study (e.g., time between initial screening and beginning of the 
intervention, which starts at the end of routine post-TKA PT).  It is unlikely that any exclusionary health 
conditions, resulting in screen failure, will resolve during that period of time.  
 
5.5.  
STRATEGIES FOR RECRUITMENT AND RETENTION  
For UNC Healthcare clinics, we will identify potential participants though regular medical record searches of 
patients initiating outpatient post-TKA PT. About 10 patients initiate post-TKA PT at our target clinics monthly. 
Although we expect this will be sufficient to meet our sample size goal, we also have existing partnerships with 
and processes for working with other local PT clinics 37. Potentially eligible patients will be mailed a recruitment 
letter (including an opt-out telephone number) from the study team, followed by a telephone call about 1 week 
later from a study team member to assess eligibility and interest. A UNC provider (physical therapist or 
orthopedic surgeon) may also discuss the study with a patient and will notify a study team member, if the 
patient agrees to be contacted.  For non UNC Healthcare physical therapy clinics, staff will provide verbal 
information and / or recruitment flyers to participants regarding the study.  With patients’ verbal permission, a 
clinic team member may provide our UNC study team with contact information (telephone number, address) for 
the patient, so that we may contact them about the study.  Patients may also directly contact the UNC study 
team, using the phone number provided on the flyer.  Interest and eligibility of these patients will also be 
assessed via telephone.  
Eligible patients will be asked to meet with a study team member to complete a baseline visit including 
informed consent, Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization and 
baseline assessments. We may review the informed consent and HIPAA over the phone prior to the baseline 
visit. At the end of the baseline visit, participants will be given an accelerometer to wear for one week and 
return via mail.  Following receipt of the accelerometer, participants will be called by an un-blinded study team 
member with their randomization assignment, and the treating therapist will be notified accordingly. 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
16 
Protocol v11.0 - 20221006  
6.0  
STUDY INTERVENTIONS  
6.1  
STUDY INTERVENTION ADMINISTRATION 
  
PAS Intervention Administration  
Overview. Traditional post-TKA PT focuses on reducing pain and swelling and increasing range of motion 
(ROM) and strength. The PAS program significantly augments usual post-TKA PT, specifically addressing 
critical gaps of physical inactivity and joint loading asymmetry. The PAS program will be initiated during the 
final usual care PT visits, allowing integration and capitalizing on the existing patient-provider relationship. This 
is strategic timing because patients typically make substantial progress in traditional metrics (strength, ROM, 
pain) by this time point and are embarking on the independent phase of the recovery process. We will aim for 
PAS content to be included within the last two routine PT visits and will orchestrate this timing with study 
physical therapists. The course of PT may end slightly sooner or later than expected, and this exploratory 
study will allow us to fine tune processes for beginning delivery of PAS. PAS participants will then receive a 
follow-up call after 4 weeks (to assist with activity progression and problem-solving) and an additional visit 
(conducted in-person if possible or remotely via an IRB approved video platform or by phone if needed) after 8 
weeks (to visually monitor exercise performance and re-assess proportional weight-bearing ability). Each of the 
contacts for the PAS intervention is summarized in Table 1 and described below. Participants will be asked to 
track performance of specific exercises and overall PA through Physiotec, a web-based tracking page. 
Physical therapists will have access to these pages to facilitate accountability and intervention delivery.  If 
participants prefer not to log their exercise using Physiotec the study team will offer paper logs that can be 
used instead.  In these cases, participants will be reminded to bring in their exercise logs for in-person 
sessions, and physical therapists will ask participants to refer to their logs during the 4-week phone call.  For 
participants who do not have regular  
internet access (expected 9-10%) 37, 
we will provide an iPad and data plan 
for the intervention period.  Physical 
therapists will also track information 
from PAS sessions through a study 
clinic note template in the participant’s 
medical record. 
 
PAS Content: Counseling to Increase 
General Physical Activity  
Specific content will be as follows: 
Session 1 (In-Person if possible, or via 
video platform or phone if needed): 
The PT will:  (1) Emphasize the 
importance of PA in TKA recovery 
using key points. (2) Work with 
participants to establish a SMART 
(Specific, Measurable, Attainable, Relevant, Time-bound) goal regarding overall PA. (3) Incorporate MI 
principles to elicit motivations and / or ambivalence toward PA 69-71. (4) Provide a list of community-based and 
other resources to support overall PA. These materials will be emailed to the participant if the visit is conducted 
remotely.   
Session 3 (4-Week Phone Session): The PT will: (1) Assess progress with overall PA using standard 
questions, referring to the web-based PA log. (2) Help participants to develop strategies to address any 
barriers they experienced in their PA. (3) Apply MI principles to elicit motivations and / or ambivalence toward 
PA. (4) Work with participants to establish a new SMART PA goal for the next four weeks, with appropriate 
progression. (5) Discuss PA resources and facilitate connection of participants to these resources.   
Table 1. Overview of PAS Intervention Session Content 
Session # 
PA Counseling Content 
Balance Exercise (Loading 
Symmetry) Content 
Total 
Minutes 
1 (In-Person  
or via video 
platform or 
phone if 
needed)) 
Overview of PA post-TKA, goal-
setting, MI 
-- 
15-20 
2 (In-Person,  
or via video 
platform or 
phone if 
needed ) 
-- 
50% weight-bearing 
exercise, assign home 
exercises 
20-25 
3 (Phone) 
4-weeks  
Assess PA, address barriers, 
goal-setting, MI, community 
resources 
Assess progress with 
exercises, advise on 
progression 
25 
4 (In-Person,  
or via video 
platform or 
phone if 
needed ) 
8-Weeks 
Assess PA, dealing with 
setbacks, MI long-term goal 
setting 
Demonstration of 
exercises, advise on 
progression 
40 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
17 
Protocol v11.0 - 20221006  
Session 4 (8-Week Session In-Person if possible or remotely via an IRB approved video platform or by phone 
if needed): Activities will mirror those for Session 3 with two modifications. First, the physical therapist will 
discuss strategies for dealing with setbacks in PA.  Second, SMART goal setting will be more long term in 
nature, focusing on the next six months.   
PAS Content: Balance Exercises to Improve Joint Loading Symmetry.  
Although usual post-TKA PT aims to improve overall function, the PAS intervention differs substantially in its 
targeted approach to help patients detect side-to-side joint loading asymmetries and re-learn how to equalize 
loads across limbs. The content for this component of PAS will be as follows: 
Session 2 (Second Session In-Person if possible, remotely via an IRB approved video platform or by phone if 
needed): If session is conducted in person, participants will undergo a process enabling them to detect when 
50% weight bearing is achieved on each leg. The foot of the post-surgical limb will be placed on an analog 
bathroom scale and the contralateral foot on a small step of equivalent height. The participant will then shift 
weight between legs so that it feels as if 50% of weight is on each foot. The therapist will inform the participant 
of the actual weight distribution and assist the participant with achieving 50% weight bearing stance through 
verbal and tactile cues. The participant will then perform a series of 10 weight shifts off of the post-surgical limb 
and attempt to return to 50% weight bearing for a 10 second hold in that position. Participants who cannot 
successfully assume equal weight bearing within 5% for 8 of 10 trials will be given a scale and a step of equal 
height to continue practice at home by performing 10 repetitions of the weight shifting activity daily.  
Next, the PT will prescribe balance 
exercises – one static and two dynamic 
(see Intervention Documents) - which 
supplement the general strengthening 
exercises assigned as part of usual post-
TKA PT.  The initial balance exercises 
prescribed will be the highest level at which 
the participant can perform at a minimal 
standard (defined in Table 2).  If the visit is 
conducted remotely, the PT will be 
instructed to begin with the lowest level of 
balance exercises and to increase the level 
once they meet the progression criterion 
shown in Table 2.  Participants will be 
given or emailed handouts and access to a 
website that displays proper exercise form. 
Participants will be instructed to perform 
exercises once daily. Static balance 
exercises will be performed bilaterally in an alternating leg manner for three repetitions, 30-seconds each, with 
use of hand support as needed to maintain balance. Dynamic balance exercises will be performed bilaterally 
for 10 repetitions per set for three sets, with use of hand support as needed.  
Session 3 (4-Week Telephone Session): The PT and participant will discuss recent performance of balance 
exercises (e.g, frequency, progression, problems with specific exercises) using standard questions (see 
Intervention Documents). This will ensure exercise performance is of appropriate intensity and frequency to 
achieve improvement. The therapist will encourage the participant to advance to the next level of an exercise 
has become too easy, based on criteria in Table 2. 
Session 4 (8-Week Session In-Person if possible or remotely via an IRB approved video platform or by phone 
if needed): The PT and participant will discuss performance of balance exercises using standard questions 
(see Intervention Documents). Participants will demonstrate current exercises if the session is conducted in 
person or via video platform, and the therapist will correct form as needed. Progression of exercises will be 
promoted as described above. If session is delivered in-person, the therapist will also reassess participants’ 
abilities to stand with equal weight bearing as described above in Session 2.  
Table 2.   PAS Intervention Balance and Functional Strength Exercises 
STATIC BALANCE 
DYNAMIC BALANCE* 
Initial Exercise: most 
challenging position that can be 
held for 3 repetitions, 10 seconds 
Initial Exercise: most challenging activity that 
can be performed for 10 consecutive repetitions 
without a loss of balance 
Progression Criterion: hold for 
30 seconds, 3 repetitions 
Progression Criterion: perform 3 sets of 10 
repetitions without a loss of balance 
Exercises (in order of difficulty) 
Staggered stance 
Weight shift in staggered 
stance 
Forward lunge  to 45 
degrees knee flexion 
and return 
Narrow staggered stance 
Weight shift in tandem 
stance 
Walking forward lunge 
Tandem stance 
Tandem walk with arms 
outstretched 
March with single leg 
hold for 3 seconds 
Single leg stance 
Tandem walk with arms 
crossed over chest 
Walking forward lunge 
with 3 seconds hold 
during transition 
*Physical therapist will assign 1 exercise from each column. 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
18 
Protocol v11.0 - 20221006  
ATT Control Intervention Administration . The ATT control group will receive usual in-person post-TKA 
care, without the additional PAS components described for Sessions 1 and 2 in Table 1. To account for non-
specific effects (e.g. therapists “attention”) of the two additional visits in the PAS intervention (4-week phone 
call and 8-week visit), the ATT control group will receive visits at the same intervals but differing in content.  
Specifically, the 4-week phone call will include: information on typical recovery benchmarks for this time point, 
assessment of participants’ daily activities, and reminders about symptoms that should trigger contacting a 
medical professional.  The 8-week visit (conducted in-person if possible or remotely via an IRB approved video 
platform or by phone) will be primarily evaluative, including assessment of ROM, strength, and function when 
possible. If the visit is delivered via video, performance tests will be conducted, when feasible.  Participants will 
be given or emailed a report summarizing these assessments. Participants will also be instructed to continue 
the home exercise program prescribed by their PT at discharge. This information may be delivered whether the 
visit is conducted in-person, via video or by phone. Neither of these contacts will include PA counseling or 
promotion of symmetrical loading of lower extremities, which are key components of the PAS intervention.   
 
6.2  
FIDELITY 
Physical therapists will be trained by Drs. Allen (PA counseling) and Hill (balance exercises) and will conduct 
mock sessions of all PAS visits prior to study initiation.  The study team and physical therapists will establish a 
formal description of usual care PT components, to help ensure the in-person ATT visits are distinct from the 
PAS visits.  Study physical therapists will also be trained in delivery of the 4- and 8-week ATT control sessions.  
Since contamination between interventions is a challenge of this study design, we will aim to conduct 
monitoring of 75% of PT sessions to evaluate fidelity and the feasibility of using this approach for a larger trial.   
 
6.3  
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING  
 
The randomization scheme will be generated by the study statistician and stored within the study database.  
The database will be configured so that blinded study personnel (e.g., those conducting follow-up 
assessments) will not have access to randomization information. The participants will not be notified of 
randomization assignment until all baseline assessments are complete.  In addition an individual participant’s 
randomization assignment will not be known to any study personnel until baseline assessments are complete. 
Randomization will be stratified according to gender and presence of self-reported pain (≥3 on a 10 point 
scale) in any lower extremity joint (hip, knee or ankle) in addition to the surgical knee, to ensure that the groups 
are balanced in these respects.   
 
6.4  
STUDY INTERVENTION ADHERENCE  
 
The study database will be used to track participants’ completion of all assessment visits, as well as all 
intervention visits.  Intervention visits will be logged in the UNC electronic medical record (EMR), and the study 
coordinator or other unblinded study team member will monitor these records for study participants to 
determine intervention adherence (and document the information in the study database).  The study team will 
also maintain close communication with study physical therapists.  If participants miss intervention visits, an 
unblinded study team member may assist the study physical therapist in contacting and rescheduling visits, as 
needed.  
 
6.5  
CONCOMITANT THERAPY 
  
Participants will be permitted to continue any other post-TKA treatment (e.g., pain medications) during the 
course of the study.  
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
19 
Protocol v11.0 - 20221006  
7  
STUDY INTERVENTION/ DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1  
DISCONTINUATION OF STUDY INTERVENTION 
 
When a participant discontinues from the PAS intervention but not from the study, remaining study procedures 
will be completed as indicated by the study protocol.  If a clinically significant finding is identified (including, but 
not limited to changes from baseline) after enrollment, the investigator or qualified designee will determine if 
any change in participant management is needed; the treating study physical therapist may be involved with 
these recommendations. Any new clinically relevant finding will be reported as an adverse event (AE). The 
data to be collected at the time of study intervention discontinuation will include the reason(s) for discontinuing 
the participant from the intervention, and methods for determining the need to discontinue. 
 
7.2  
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY  
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue a participant from the study for the following reasons: 
 
• 
Lost-to-follow up; unable to contact subject  
• 
Any event or medical condition or situation occurs such that continued collection of follow-up  study 
data would not be in the best interest of the participant or might require an additional treatment that 
would confound the interpretation of the study 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) that 
precludes further study participation 
The reason for participant discontinuation or withdrawal from the study will be recorded in the study database.   
Participants who discontinue or are withdrawn will be replaced up to the point of randomization assignment 
being given to the participant.  Once participants are given their randomization assignment, they will be 
counted toward the total study sample size and not replaced.  
 
7.3  
LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to return for the final, 6-month follow-up 
assessment.  If a participant misses intervention visits or misses the 3-month follow-up assessments and 
cannot be contacted during the time frame, the study team will still attempt to contact the participant for 
remaining visits / assessments. The study team must attempt to contact a participant at least 3 times, on 
different days of the week, different times of day, and across at least 2 weeks, before they are considered to 
have missed a visit / assessment or are lost to follow-up.  These contact attempts will be documented in the 
study database.  
 
8   
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1  
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
Measures will be collected at baseline, 3 months and 6 months by a trained research assistant blinded to 
randomization assignment. Participants will be paid $50 for completing baseline questionnaire and $15 for 
wearing and returning an accelerometer. Then, up to $40 at 3 month and 6 month time point: $25 for 
completing questionnaires and functional measures and $15 for wearing and returning an accelerometer. 
Due to COVID-19 safety measures, we may conduct a briefer set of measures focused on the primary 
functional assessments.  We will explain to the participant during the consent process that the measures may 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
20 
Protocol v11.0 - 20221006  
be more limited in order to minimize in-person visit time. Also, we may schedule a time to call the participant 
after the in-person visits (at baseline and 3 month and 6 month follow-up) to complete the questionnaires over 
the phone.   
  
Efficacy (Aims 1 and 2) 
Co-Primary Efficacy Outcome: Objectively Assessed Physical Activity (accelerometer). Our specific primary 
outcome of interest is MVPA per week, since this corresponds to DHHS recommendations and is a known 
predictor of outcomes in patients with OA 7. We will also examine step counts, minutes of any PA and 
sedentary minutes as secondary outcomes 72,73. Participants will wear the waist-worn Actigraph GT3X+ 
(Pensacola, FL) for 7 days 74. Following previously established thresholds, outcomes will only be computed for 
participants who wear the accelerometer for 4+ days with 10+ hours of wear. Accelerometers will be given to 
participants during in-person visits at each time point and mailed back to the study team, using our procedures 
from prior studies that have resulted in very high adherence rates (89-93%). If participants are not able to 
complete follow-up assessments in person but complete questionnaires by telephone, we may mail an 
accelerometer for wear and return via mail. Accelerometer data will be processed using standard procedures 
75-78.   
Co-Primary Efficacy Outcome: Peak Joint Load Symmetry During Walking. We will use a novel, 3-sensor in-
shoe load measurement device (loadsol) to measure joint load symmetry. The loadsol® builds on the reliable 
pedar-X® in-shoe measurement system 79 but importantly collects data on a handheld device without any 
external cabling, facilitating measurement during a variety of dynamic tasks. The loadsol® requires minimal 
training, making it ideal for clinical settings. Participants will complete a 10 meter walking test (three trials 
averaged) 80, while load beneath each foot is recorded. Walking speed will also be recorded and will be used 
as a covariate since this may impact the loading metrics. Loading symmetry (peak ground reaction force) will 
be assessed using the limb symmetry index (LSI (|Surgical/Non-Surgical|*100), which has been associated 
with adverse outcomes such as re-injury of the anterior cruciate ligament (ACL); values lower than 100% 
indicate less loading of the surgical limb 81-84. LSI was selected based on its current use in the clinical setting 
and the ease of calculation.  
Secondary Efficacy Outcomes 
Self-reported Physical Activity:  Modified version of the CHAMPS (Community Health Activities Model Program 
for Seniors) Physical Activity Measure 85.   This measure complements the accelerometer-based data by 
providing additional information on the contexts and types of activities in which participants are engaging. This 
modified version of the CHAMPS includes items tailored for this participant group.  For each item, participants 
first indicate whether they have done the activity for 10 or more minutes during the past week.  If they respond 
“yes,” they will be asked the number or days and minutes per week. This questionnaire will be supplemented 
with individual items to assess sitting behavior and sleep.   
 
Physical Performance Tests. We will administer tests recommended by OARSI for clinical trials of knee OA: 
30-second stair stand test, 40m fast-paced walk, stair climb test, and TUG test 86 . Participants will wear the 
loadsol bilaterally for all functional tests. This will allow us to assess loading symmetry while patients are 
performing each of these common daily tasks.  In addition, for the 30-second chair stand test, TUG, and 10m 
walk (described above), we will collect additional measures for the purpose of developing field-based methods 
for assessing knee joint kinematics and spatiotemporal gait mechanics.   
 
Data capture via video cameras discontinued in December 2021 Three high speed cameras will be used to 
record participants completing the function tests. All cameras will be placed on tripods held 60 cm off the floor. 
One camera will be placed facing the participant and 150 cm beyond the line in which they turn during the 
TUG. The other two cameras will be placed to the left and right of the middle of the TUG path approximately 
350 cm away from the path. Participants will be equipped with 6 reflective markers, which will be placed 
bilaterally over the lateral aspect of the femoral epicondyle, in the middle of the shank in-line with the lateral 
femoral epicondyle and lateral malleoli, and in the middle of the thigh in-line with the lateral femoral epicondyle 
and greater trochanter. Each camera will be equipped with an external light source (flash), which will cause the 
reflective markers to shine very brightly and be easily tracked throughout the video. The cameras will collect 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
21 
Protocol v11.0 - 20221006  
wide view videos at 120 frames per second. The wide view video will result in a ‘Fish-Eye’ effect in the video 
data, which will be corrected and converted to a linear image using previously developed methods23, 26 and the 
individual cameras lens coefficients. Each marker will be tracked in both the frontal and sagittal view videos 
after de-warping the fish-eye effect. The XY position of each marker will be used to create knee angles. Before 
movement trials, a 1 second static trial will be recorded from both views, and the knee angle during quiet 
stance will be used to normalize knee angle during the movement trials (i.e. knee flexion and valgus will be 
considered zero during quiet stance). 
 
Balance. We are conducting a limited set of tests due to COVID precautions. We will administer two tests from 
the Berg Balance Scale: tandem stance and 10 sec single leg stance 87. We will also administer one test from 
the Brief Balance Evaluation Systems Test:  Stance With Eyes Closed, on Foam Surface 88.   
 
Knee injury and Osteoarthritis Outcome Score (KOOS).  The KOOS is a widely used and validated patient-
reported outcome that includes five separately scored subscales (42 items total): pain, symptoms, activities of 
daily living, sports and recreation, and knee-related quality of life  90.  The KOOS pain subscale will also be 
assessed at each intervention visit, so that we can assess potential associations between pain and PA.   
 
Tampa Scale for Kinesiophobia. Fear of movement is a key concern for patients following TKA, associated with 
poorer clinical outcomes 91,92.  This is a 17-item measure of multiple domains of fear of movement 93.   
Feasibility and Acceptability (Aim 3) 
 
Feasibility Metrics, The following are feasibility metrics, as well as “targets” that will indicate success, when 
appropriate: 
- Number of potentially eligible patients identified from the medical record during the recruitment period. There 
is no standard benchmark for “success” for this metric.  Rather, this information is important in planning for a 
future, larger trial.  When planning for that trial, a sample size / power analysis will be conducted.  Based on 
information gathered from this metric, we will be able to ascertain the feasibility of conducting a single site trial 
vs. moving to a multi-site trial (and understanding the number / size of sites that would be needed).  
- Proportion of patients who are eligible and enroll, along with ineligibility and refusal reasons. Similarly, there 
is no standard benchmark for success for this metric, but it will be used to determine feasibility and site(s) for a 
future trial.  However, based on our prior studies, we expect an enrollment rate of at least 20%39,94.  An 
enrollment rate below this threshold will signal a need to closely evaluate study requirements for participants, 
as well as recruitment and enrollment methods. Information gathered on ineligibility and refusal reasons will 
guide this process. 
- Proportion of participants completing each intervention contact and follow-up assessment (overall and by 
study arm). Because this is a brief intervention, completion of all 4 visits is optimal. However, we recognize 
there are reasons that participants cannot complete visits. With regard to the first two intervention visits (which 
take place during routine post-TKA PT), we will consider the approach to be successful if ≥80% of participants 
complete both visits; a proportion below this threshold will signal a need to re-evaluate our approach of how 
these interventions are embedded into routine post-TKA PT.  With regard to the 4-week and 8-week follow-up 
intervention visits, we will also consider the approach to be successful if 80% of participants complete both 
visits; a proportion below this will signal a need to re-evaluate aspects including the timing of the visits and 
whether the final visit should remain in-person vs. via telephone.  Our participant questionnaires on 
intervention feedback will provide insight into these issues.  
 
Acceptability. We will ask study participants and therapists a series of open-ended questions to assess 
intervention acceptability and obtain suggestions for improving the intervention95,96.   
Patient Characteristics. We will collect information on age, race / ethnicity, education, work and marital status, 
body mass index, comorbid illnesses 97, joints with arthritis symptoms, and duration of knee symptoms.  
Symptoms and Events in the Non-Surgical Limb.  Although the 6-month follow-up period is not sufficient to fully 
assess impacts on the non-surgical limb, we will measure changes in pain (10-point visual analog scales 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
22 
Protocol v11.0 - 20221006  
specific to the contralateral knee, assessing average, worst and least pain in the past 2 weeks), injuries, and 
progression in plans for TKA. This will be assessed for a longer period in the subsequent larger trial. 
 
8.2  
SAFETY ASSESSMENTS 
Study physical therapists will be experienced clinical personnel who are familiar with standard clinical practice 
for protecting patient safety during visits.  Study-specific intervention content is within the scope of PT practice, 
so we do not believe any special procedures are needed to protect participants’ safety, beyond adherence to 
usual procedures.  For the weight-shifting exercise to be conducted in 2 of the PAS visits, we will provide 
physical therapists with in-person training and a video (to refer to at later points) to show procedures, including 
prevention of falls if a participant loses their balance during the test.  In addition, when participants are shown 
balance exercises, the physical therapists will instruct them to perform these in a place where they can easily 
grab on to a stable item if they begin to lose balance.  Any AEs that occur during PT visits or in the course of 
participants’ home exercise will be documented on the Adverse Events form, as described below.  
 
For the Physical Performance Tests, the testing administrator will be trained to monitor patient safety during 
testing. This will include following slightly behind and off to one side of the patient but not to pace or impede 
them, as well as allowing the patient to stop and rest if they become tired, if necessary.   
 
8.3  
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS  
 
8.3.1 DEFINITION OF ADVERSE EVENTS 
This protocol uses the definition of adverse event from DHHS Office for Human Research Protections (OHRP): 
Any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for 
example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the 
subject’s participation in the research, whether or not considered related to the subject’s participation in the 
research (modified from the definition of adverse events in the 1996 International Conference on 
Harmonization E-6 Guidelines for Good Clinical Practice). 
 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
This protocol uses the definition of serious adverse event from DHHS OHRP: any adverse event that results in 
death; is life-threatening (places the subject at immediate risk of death from the event as it occurred); results in 
inpatient hospitalization or prolongation of existing hospitalization; results in a persistent or significant 
disability/incapacity; results in a congenital anomaly/birth defect; or based upon appropriate medical judgment, 
may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the 
other outcomes listed in this definition (examples of such events include allergic bronchospasm requiring 
intensive treatment in the emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse). 
 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
 
 
 
8.3.3.1 SEVERITY OF EVENT 
All AEs will be assessed by the PI or co-investigators, if the PI is not available.  The following guidelines will be 
used to describe severity:  
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
23 
Protocol v11.0 - 20221006  
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic measures. 
Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy or 
other treatment. Severe events are usually potentially life-threatening or incapacitating.  Of note, the 
term “severe” does not necessarily equate to “serious”.] 
 
 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
All AEs will have their relationship to study procedures, including the intervention, assessed by the PI or co-
investigators based on temporal relationship and his/her clinical judgment. The degree of certainty about 
causality will be graded using the categories below.  
 
• 
Related – The AE is known to occur with the study procedures, there is a reasonable possibility that 
the study procedures caused the AE, or there is a temporal relationship between the study procedures 
and the event. Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study procedures and the AE. 
• 
Not Related – There is not a reasonable possibility that the study procedures caused the event, there 
is no temporal relationship between the study procedures and event onset, or an alternate etiology has 
been established. 
 
 
 
8.3.3.3 EXPECTEDNESS 
A clinician with appropriate expertise in post-TKA patients and recovery (Olcott or Hill) will be responsible for 
determining whether an AE is expected or unexpected. An AE will be considered unexpected if the nature, 
severity, or frequency of the event is not consistent with the risk information previously described for the study 
procedures. 
 
 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an AE or serious adverse event (SAE) may come to the attention of study team members 
during study visits.  All AEs, not otherwise precluded per the protocol, will be captured on the Adverse Event 
Form.  Information to be collected includes event description, time of onset, clinician’s assessment of severity, 
relationship to study procedures (assessed only by those with the training and authority to make a diagnosis), 
and time of resolution/stabilization of the event. All AEs occurring while on study will be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
Any medical or psychiatric condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition deteriorates at 
any time during the study, it will be recorded as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event at 
each level of severity to be performed. Documentation of onset and duration of each episode will be 
maintained for AEs characterized as intermittent. 
The Project Coordinator will record events with start dates occurring any time after informed consent is 
obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation.  
Participants are identified in the EMR as a study participant and for each AE/SAE occurrence, research team 
members will receive an alert through EMR. AEs or SAEs may also be reported to study physical therapist 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
24 
Protocol v11.0 - 20221006  
during the course of intervention visits.  Events will be followed for outcome information until resolution or 
stabilization. 
 
 
8.3.5  ADVERSE EVENT REPORTING 
Once Dr. Allen (or a co-investigator) is contacted about the adverse event, she / he will make a determination 
about the reporting requirements in accordance with UNC IRB guidelines.   
The PI will report all adverse events to the Safety Officer (SO) on a biannual basis, or as requested. 
Additionally, the PI or a co-investigator will report any AEs that suggest new or increased risk to participants or 
others within 7 calendar days of when the PI became aware of the information.  For AEs that are not related to 
participation in the research and do not suggest new or increased risks to the participant, these will be reported 
at continuing review.    
 
 
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING 
Once Dr. Allen (or a co-investigator) is contacted about a serious adverse event, she / he will make a 
determination about the reporting requirements in accordance with UNC IRB guidelines.  This will include 
notification of the UNC IRB, as well as the SO, within 24-hours if a study-related death and within 48 hours if 
another SAE.  
 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS 
N/A 
 
 
8.3.8  EVENTS OF SPECIAL INTEREST 
N/A 
 
 
8.3.9 REPORTING OF PREGNANCY   
N/A 
 
8.4. 
UNANTICIPATED PROBLEMS 
 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
 
Unanticipated Problems (UPs) are not included in the 45 CFR part 46, but are defined by the OHRP as any 
incident, experience or outcome that meets all of the following requirements:  
 
(1) Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures that are 
described in the IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the participant population being studied; 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
25 
Protocol v11.0 - 20221006  
(2) Related or possibly related to participation in the research. Possibly related means there is a reasonable 
possibility that the incident, experience, or outcome may have been caused by the procedures involved in 
the research); and 
 
(3) Suggests that the research places participants or others at a greater risk of harm (including physical, 
psychological, economic, or social harm) than was previously known or recognized. 
 
OHRP recognizes that it may be difficult to determine whether a particular incident, experience, or outcome is 
unexpected and whether it is related or possibly related to participation in the research.  OHRP notes that an 
incident, experience, or outcome that meets the three criteria above generally will warrant consideration of 
substantive changes in the research protocol or informed consent process/document or other corrective 
actions in order to protect the safety, welfare, or rights of participants or others.   
 
The following corrective actions or substantive changes that could be considered in response to an 
unanticipated problem include:  
 
o 
Changes to the research protocol initiated by the investigator prior to obtaining IRB approval to 
eliminate apparent immediate hazards to subjects;  
o 
modification of inclusion or exclusion criteria to mitigate the newly identified risks; 
o 
implementation of additional procedures for monitoring subjects; suspension of enrollment of new 
subjects;  
o 
suspension of research procedures in currently enrolled subjects;  
o 
modification of informed consent documents to include a description of newly recognized risks;  
o 
provision of additional information about newly recognized risks to previously enrolled subjects. 
 
Only a small subset of adverse events occurring in human subjects participating in research will meet these 
three criteria for an unanticipated problem. Furthermore, there are other types of incidents, experiences, and 
outcomes that occur during the conduct of human subjects research that represent unanticipated problems but 
are not considered adverse events.  For example, some unanticipated problems involve social or economic 
harm instead of the physical or psychological harm associated with adverse events.  In other cases, 
unanticipated problems place subjects or others at increased risk of harm, but no harm occurs.   
 
 
8.4.2 UNANTICIPATED PROBLEMS REPORTING 
All UPs will be reported to the NIAMS and the SO (through KAI) within 48 hours of the PI becoming aware of 
the event. 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS 
Participants will be given any new information gained during the course of the study that might affect their 
willingness to continue participation in the study.  
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
26 
Protocol v11.0 - 20221006  
9  
STATISTICAL CONSIDERATIONS 
 
9.1  
STATISTICAL HYPOTHESES 
 
Specific Aim 1:  Obtain preliminary data on the efficacy of the PAS program with respect to the change 
in objectively assessed physical activity, measured via 
accelerometers. 
H1:   The PAS group will have greater improvement in objectively 
assessed physical activity at the 3-month and 6-month assessments, 
compared to the ATT control group. The main co-primary metric of 
interest is MVPA; other secondary metrics will include step count, minutes of any PA, and sedentary minutes.    
Specific Aim 2:  Obtain preliminary data on the efficacy of the PAS program with respect to change in 
peak load symmetry during walking, measured by a novel 3-sensor insole device.  
H2: The post-TKA exercise group will have greater improvement in peak load symmetry during walking at the 
3-month and 6-month assessments, compared to the attention control group. The main co-primary outcome of 
interest will be the peak load - limb symmetry index during level walking; secondary outcomes will be peak load 
- limb symmetry index values during additional physical performance tasks.       
 
9.2  
SAMPLE SIZE DETERMINATION 
 
No adjustment for co-primary outcomes is made since this is a pilot study.  We do not necessarily expect this 
exploratory study to be highly powered. Table 3 shows a range of effect sizes and corresponding statistical 
power for a comparison of intervention versus control group means, for the projected total of n=54 participants 
at the two-sided 0.05 significance level. We chose n=54 because this is reasonable to complete within the time 
frame of this exploratory trial and will allow sufficient experience to inform a larger trial.  We are allowing for a 
10% attrition rate, so n=60 participants will be enrolled. Data from this study are crucial for informing sample 
size estimates for a larger trial; however, preliminary calculations indicate that for a standardized effect size of 
0.35-0.40 standard deviation units, a sample size of 100-130 per group may be required.  This sample size is 
reasonable to enroll within the time frame of this exploratory trial, and it will allow sufficient experience with 
intervention delivery to inform the larger trial.   Our analytic strategy (described below) will also accommodate 
dropout, missed visits, and loss-to-follow-up.  Information regarding the actual observed extent of dropout, 
missed visits, and loss-to-follow-up in this study will also be useful for the subsequent large-scale trial. 
 
9.3  
POPULATIONS FOR ANALYSES 
 
The primary analyses will be conducted using an intent-to-treat approach.  Supportive exploratory analyses 
may be conducted to consider samples with greater completion of study intervention visits.  Since this is a 
preliminary, exploratory analysis, the nature of these supportive analyses will be based on observed patterns 
of intervention visits. However, likely approach is to assess outcomes among participants who completed at 
least 3 of the 4 study visits.  
 
9.4  
STATISTICAL ANALYSES PLAN  
 
Preliminary analyses will include generating descriptive statistics for demographic variables, as well as 
baseline characteristics and follow-up measures.  This includes means and standard deviations for continuous 
variables, and frequencies and percentages for categorical variables.  Ranges will also be examined for 
outliers and to ensure data integrity. Demographics and baseline characteristics will also be described 
separately by randomized group.  Statistical tests will be performed to compare each of these by randomized 
group to determine the extent of random imbalance by t-test of chi-square testing, as appropriate.  However, 
the p-values generated by these tests are considered as descriptive rather than as inferential.  We would 
Table 3. Statistical power according to effect 
size, assuming 27 patients per group 
Effect Size (SD units) 
0.5 
0.6 
0.7 
0.8 
0.9 
1.0 
0.44 
0.66 
0.58 
0.82 
0.90 
0.95 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
27 
Protocol v11.0 - 20221006  
expect some imbalance between the groups by random chance, owing to the limited sample size.  Variables 
exhibiting imbalance may be considered as covariates in the statistical models described below. 
 
The co-primary outcome of MVPA will be analyzed across the follow-up time points through a general linear 
mixed model (GLMM).  Specifically, the MVPA values at 8 weeks and at 6 months for a given patient will form 
their response vector for this model.  Fixed effects for the primary model will include an indicator for PAS 
group, an indicator for the 6-month follow-up time point, their interaction (group by time), and baseline MVPA 
value; a supporting model will also include any covariates that exhibit random imbalance between groups at 
baseline. Random effects for patients will account for the within-patient correlation induced by the repeated 
measures design. Formal statistical testing of the group by time interaction term will provide assessment for 
whether efficacy varies by follow-up time point. A term representing the interaction of PAS-by-baseline value 
will be included and tested to explore whether participants’ starting point might impact how much they improve; 
it will be removed if non-significant attention.  Statistical contrasts will be constructed in order to estimate the 
effect of PAS versus attention control, separately at 8 weeks and at 6 months; these estimates will inform the 
sample size estimation of the subsequent trial.  Estimated correlations among follow-up time points will also be 
useful in this regard.   
The approach outlined above will be repeated for the co-primary outcome of peak joint loading symmetry 
during gait, through fitting a separate GLMM.  The main difference will be to include walking speed as an 
additional covariate, as justified in the research strategy.  Secondary outcomes will also be analyzed using the 
same approach, each with its own GLMM.  
  
 
An exploratory analysis will include KOOS pain scores as a (time-dependent) main effect, as well as their 
interaction with PAS, to evaluate whether this variable has an impact on intervention effects. This exploratory 
analysis will be repeated, but using participant-specific changes in KOOS pain scores, to examine how our 
primary outcomes (MVPA and peak load symmetry during walking) are associated with those changes.  
  
If any of the co-primary or secondary outcomes exhibit distributions that deviate markedly from normality, 
alternatives will be considered.  First, transformations, such as the natural logarithm, will be applied in an 
attempt to normalize the distribution.  If this is not successful in remedying the non-normality, alternatives such 
as categorizing the variable and applying appropriate categorical data analysis, such as logistic mixed models 
(with a similar specification as described above for the GLMMs) or logistic models utilizing generalized 
estimating equations methodology can be fitted. 
 
A two-sided 0.05 significance level will be applied to each co-primary outcome, as well as each secondary 
outcome; no adjustment for multiple comparisons will be applied.  This is consistent with the trial’s objective as 
a pilot study to generate estimates useful for the large-scale trial to follow. 
 
An additional advantage to using the GLMM approach is its ability to accommodate missing data (including 
dropouts, missed visits, and lost-to-follow-up) under a missing at random paradigm.  All available follow-up 
data will be utilized in an intent-to-treat manner.  If a participant is missing one of the follow-up time points, that 
participant is not completely excluded from the analysis. A supportive analysis will be conducted using multiple 
imputation to produce multiple datasets that have complete data for all n=60 participants, where missing 
values (due to dropouts, missed visits, and lost-to-follow-up) have been imputed.  The statistical models will be 
fitted to each of the complete datasets; results of each model will be synthesized in a manner that accounts for 
both between and within imputation variation to produce final estimates to address the research questions. 
 
Feasibility metrics will be computed as proportions, along with 95% confidence intervals to describe the level of 
uncertainty of the estimates.  Lower confidence bounds of these proportions will be useful in considering worst-
case scenarios when planning the subsequent large-scale trial. Acceptability data are primarily open-ended 
questions, and responses will be summarized to inform appropriate modifications to the PAS intervention. For 
the brief questionnaires on acceptability, appropriateness, and feasibility 95,96, we will calculate mean and 
median scores and distributions across each domain.   

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
28 
Protocol v11.0 - 20221006  
 
10  
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Consent forms describing in detail the study intervention, study procedures, and risks will be given to the 
participant and written documentation of informed consent will be completed prior to starting the study 
intervention.  The following consent materials are submitted with this protocol: Adult Consent Form.  
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
Once a potential participant meets the medical record and telephone screening criteria for eligibility, and is 
interested in participating, a study team member will email or mail the potential participant a copy of the 
informed consent form and HIPAA for them to review.  The study team member will set up a time to call the 
potential participant no more than 24 hours before the baseline visit to conduct the COVID-19 wellness 
screening.  During the phone call, the study team member will review the IRB approved consent form with the 
potential participant and provide an opportunity for him/her to ask any questions that they may have about the 
research study.  
 
We will use a UNC IRB approved consent form with included language that satisfies the HIPAA requirements 
and outlines the protection of health information utilized in the study.  No other study activities will occur until 
the consent process is completed.   
 
We anticipate this process to take approximately 20 minutes, but this time will not be limited should a 
participant have additional questions or concerns regarding the study.  During this phase of the consent 
process, it will be stressed that the participant is not obligated to participate in the study, that participation is 
completely voluntary, and that he/she may withdrawal from the study at any time without penalty.  Also, 
potential risks from participating in the study will be outlined in the consent form, as are the measures taken to 
protect against study specific risks.  Once the information in the consent from is fully reviewed and understood 
by the individual, he/she will be asked to decide at that time if they would like to voluntarily participate in the 
research study.  If the individual does choose to participate in the study, they will be asked to print, sign and 
date the consent form and HIPAA, and bring the documents with them to the baseline visit.  If the participant is 
unable to print or bring the documents, copies will be available at the baseline visit for them to complete.  Both 
the individual and the study team member will sign and date the consent form.  Each enrolled participant will 
then receive a signed copy of their consent form to keep for their records.   
 
If after reviewing the consent form, the potential participant is not sure they would like to participate in the study 
at this time, they may choose to consider the study further at home, and then contact the study team if they 
decide later that they would like to participate.  
 
Participants will only be included if they have capacity to give legally effective consent. Additionally, this study 
will only recruit participants whom are English speakers.   
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
29 
Protocol v11.0 - 20221006  
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to study participants, investigator, funding agency, and regulatory authorities. 
If the study is prematurely terminated or suspended, the PI will promptly inform study participants, the IRB, and 
sponsor/funding agency and will provide the reason(s) for the termination or suspension. Study participants will 
be contacted, as applicable, and be informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
The study may resume once concerns about safety, protocol compliance, and data quality are addressed, and 
satisfy the funding agency, sponsor, IRB or other relevant regulatory or oversight bodies (OHRP, SO). 
 
10.1.3 CONFIDENTIALITY AND PRIVACY 
 
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their staff, the 
safety and oversight monitor(s), and the sponsor(s) and funding agency. This confidentiality is extended to the 
data being collected as part of this study. Data that could be used to identify a specific study participant will be 
held in strict confidence within the research team. No personally-identifiable information from the study will be 
released to any unauthorized third party without prior written approval of the sponsor/funding agency.  
 
All research activities will be conducted in as private a setting as possible in the EXSS Lab or at a study PT 
clinic. 
 
The study monitor, other authorized representatives of the sponsor or funding agency, representatives of the 
IRB, regulatory agencies or representatives from companies or organizations supplying the product, may 
inspect all documents and records required to be maintained by the investigator, including but not limited to, 
medical records (office, clinic, or hospital) and pharmacy records for the participants in this study.  
 
The study participant’s contact information will be securely stored on a secure study database for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as long a 
period as dictated by the reviewing IRB, Institutional policies, or sponsor/funding agency requirements. 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will be 
stored on a secure UNC server. The study data entry and study management systems used by research staff 
will be secured and password protected. At the end of the study, all study databases will be de-identified and 
archived on a secure UNC server. 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
30 
Protocol v11.0 - 20221006  
Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data Sharing Policies  
It is NIH policy that the results and accomplishments of the activities that it funds should be made available to 
the public (see https://grants.nih.gov/policy/sharing.htm). The PI will ensure all mechanisms used to share data 
will include proper plans and safeguards for the protection of privacy, confidentiality, and security for data 
dissemination and reuse (e.g., all data will be thoroughly de-identified and will not be traceable to a specific 
study participant). Plans for archiving and long-term preservation of the data will be implemented, as 
appropriate.  
 
Certificate of Confidentiality  
To further protect the privacy of study participants, the Secretary, Health and Human Services (HHS), has 
issued a Certificate of Confidentiality (CoC) to all researchers engaged in biomedical, behavioral, clinical or 
other human subjects research funded wholly or in part by the federal government.  Recipients of NIH funding 
for human subjects research are required to protect identifiable research information from forced disclosure per 
the terms of the NIH Policy (see https://humansubjects.nih.gov/coc/index). As set forth in 45 CFR Part 
75.303(a) and NIHGPS Chapter 8.3, recipients conducting NIH-supported research covered by this Policy are 
required to establish and maintain effective internal controls (e.g., policies and procedures) that provide 
reasonable assurance that the award is managed in compliance with Federal statutes, regulations, and the 
terms and conditions of award. It is the NIH policy that investigators and others who have access to research 
records will not disclose identifying information except when the participant consents or in certain instances 
when federal, state, or local law or regulation requires disclosure. NIH expects investigators to inform research 
participants of the protections and the limits to protections provided by a Certificate issued by this Policy. 
 
10.1.4 FUTURE USE OF STORED DATA 
 
Data collected for this study will be analyzed and stored on a secure UNC server. After the study is completed, 
the de-identified data will be made available to other researchers, available by request to the PI. Investigators 
requesting study data must adhere to regulatory requirements for data use (e.g., IRB approvals, data use 
agreements). No biological samples are collected for this study. 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Independent Safety Monitor 
Kelli D. Allen, PhD 
Kurt P. Spindler, M.D. 
Vice-Chair of Research, Orthopaedic &   
Rheumatologic Institute (ORI) 
University of North Carolina at 
Chapel Hill  
Cleveland Clinic Sports Health Center 
3300 Thurston Bldg, CB #7280 
Chapel Hill, NC  27599-7280 
5555 Transportation Blvd. Garfield 
Heights, OH 44125 
919-966-0558 
 
kdallen@med.unc.edu 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
31 
Protocol v11.0 - 20221006  
 
 
10.1.6 SAFETY OVERSIGHT 
Safety oversight will be under the direction of the NIAMS appointed SO. The SO will be independent from the 
study conduct and free of conflict of interest. On a biannual basis, the PI will provide to the SO a study 
summary, a report of all AEs, and any problems or issues that have been identified.   
 
10.1.7 CLINICAL MONITORING 
 
Since this is a single site study there will not be site visits conducted by the PI or co-investigators.  
However, we will employ an intensive fidelity monitoring process for the study physical therapists.  
Physical therapists will be trained by the PI and a co-investigator (Hill) and will conduct mock 
sessions of all PAS and ATT control intervention sessions prior to study initiation.  Since 
contamination between interventions is a challenge of this study design, we will aim to conduct 
monitoring of 75% of PT sessions to evaluate fidelity and the feasibility of using this approach for a 
larger trial.   KAI may conduct a site visit on behalf of the NIAMS, however, KAI will not have the 
responsibility of the overall clinical monitoring for this study.  
 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Quality control (QC) procedures will be implemented as follows: 
 
Informed consent --- During the consenting process, the study team member will review the completed consent 
document to ensure the participant has signed and dated the consent form accurately prior to completing any 
other study activities.   
 
Source documents and the electronic data --- Data from the Physical Performance Tests will be initially 
captured on source documents and will ultimately be entered into the study database; all other data from study 
measures will be entered directly into the study database.  To ensure accuracy site staff will compare a 
representative sample of source data against the database. 
 
Intervention Fidelity — Consistent delivery of the study interventions will be monitored throughout the 
intervention phase of the study. Procedures for ensuring fidelity of intervention delivery are described in Section 
6.2  
 
Protocol Deviations – The study team will review protocol deviations on an ongoing basis and will implement 
corrective actions when the quantity or nature of deviations are deemed to be at a level of concern. 
 
Should independent monitoring become necessary, the PI will provide direct access to all trial related sites, 
source data/documents, and reports for the purpose of monitoring and auditing by the sponsor/funding agency, 
and inspection by local and regulatory authorities. 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
32 
Protocol v11.0 - 20221006  
 
10.1.9 DATA HANDLING AND RECORD KEEPING 
 
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
Study data will be stored on a secure UNC server in a folder accessible only to IRB-approved study team 
members. We will use REDCap to store all patient information and dispositions, responses to screening and 
outcome assessments. REDCap is a secure web application supported at UNC that can be used to build and 
manage case report forms, surveys, and other data capture mechanisms.  Additionally, a data set will be 
shared with Dr. Queen at Virginia Tech for the purpose of this research. This data set will include information 
from the loadsol measurements, for which Dr. Queen has specialized programs for analysis, along with a 
participant ID so that the processed loadsol data can be linked back with other participant data at UNC. There 
will be no additional identifiable data elements included in the data set sent to Virginia Tech.  
 
 
10.1.9.2 STUDY RECORDS RETENTION 
 
Research study records will be maintained for no less than 6 years following the completion of the study, after 
which time personal identifying information will be removed.  Research information in a subject’s medical 
record will be kept indefinitely. No records will be destroyed without the written consent of the sponsor/funding 
agency, if applicable. It is the responsibility of the sponsor/funding agency to inform the investigator when 
these documents no longer need to be retained. 
 
 
10.1.10 PROTOCOL DEVIATIONS 
 
This protocol defines a protocol deviation as any noncompliance with the clinical trial protocol,  
ICH GCP, or Manual of Procedures (MOP) requirements. The noncompliance may be either on the part of the 
participant, the investigator, or the study site staff. As a result of deviations, corrective actions will be 
developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
Section 4.5 Compliance with Protocol, subsections 4.5.1, 4.5.2, and 4.5.3  
• 
Section 5.1 Quality Assurance and Quality Control, subsection 5.1.1  
• 
Section 5.20 Noncompliance, subsections 5.20.1, and 5.20.2.  
 
It will be the responsibility of the site investigator to use continuous vigilance to identify and report deviations 
that impact participant safety to the NIAMS and the SO (through KAI) within 48 hours of the PI becoming 
aware of the event and to the UNC IRB within 7 business days of the time the PI becomes aware to the event, 
if the protocol deviation harmed participant(s) or others or placed participant(s) or others at increased risk of 
harm. Otherwise, protocol deviations/violations that occur but do not affect participant safety will be submitted 
with the routine safety reports as noted. Protocol deviations will be sent to the reviewing IRB per their policies. 
The site investigator will be responsible for knowing and adhering to the reviewing IRB requirements. Further 
details about the handling of protocol deviations will be included in the MOP. 
 
 
10.1.11 PUBLICATION AND DATA SHARING POLICY 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
- 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to 
the published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
33 
Protocol v11.0 - 20221006  
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, 
this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to 
ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals.  Data 
from this study may be requested from other researchers after the completion of the primary endpoint by 
contacting the study PI.  Considerations for ensuring confidentiality of these shared data are described in 
Section Error! Reference source not found. 
 
 
10.1.12 CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual conflict 
of interest of persons who have a role in the design, conduct, analysis, publication, or any aspect of this trial 
will be disclosed and managed. Furthermore, persons who have a perceived conflict of interest will be required 
to have such conflicts managed in a way that is appropriate to their participation in the design and conduct of 
this trial. The study leadership in conjunction with the NIAMS has established policies and procedures for all 
study group members to disclose all conflicts of interest and will establish a mechanism for the management of 
all reported dualities of interest. 
 
10.2 
ADDITIONAL CONSIDERATIONS 
N/A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
34 
Protocol v11.0 - 20221006  
10.3  ABBREVIATIONS 
 
ACL 
Anterior Cruciate Ligament 
AE 
Adverse Event 
ATT 
Attention Control  
DHHS 
Department of Health and Human Services 
CoC 
Certificate of Confidentiality 
CHAMPS 
Community Health Activities Model Program 
for Seniors 
CFR 
Code of Federal Regulations 
EMR 
Electronic Medical Record 
EXSS 
Exercise and Sports Science 
GLMM 
General Linear Mixed Model 
GCP 
Good Clinical Practice 
HHS 
Health and Human Services  
HIPAA 
Health Insurance Portability and 
Accountability Act of 1996 
ICH 
International Council on Harmonisation  
IRB 
Institutional Review Board 
KOOS 
Knee injury and Osteoarthritis Outcome 
Score 
LSI 
Limb Symmetry Index 
MOP 
Manual of Procedures 
MI  
Motivational Interviewing  
MVPA 
Moderate to Vigorous Intensity Physical 
Activity 
NIH  
National Institutes of Health 
OA 
Osteoarthritis 
OARSI 
Osteoarthritis Research Society International  
OHRP 
Office for Human Research Protections 
ORBIT 
Obesity-Related Behavioral Intervention 
Trials 
PA 
Physical Activity 
PAS 
Physical Activity and Symmetry 
PT 
Physical Therapy 
PI 
Principal Investigator 
QC 
Quality Control 
ROM 
Range of Motion 
SAE 
Serious Adverse Event 
TKA 
Total knee arthroplasty 
UNC 
University of North Carolina 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
35 
Protocol v11.0 - 20221006  
10.4 
PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change  
Brief Rationale 
2.0 
2/13/20 
Added language for provider 
referrals; added additional 
enrollment site; removed phone 
call language from fidelity checks 
Changes made to assist with 
recruitment efforts; Removed 
phone call language since 
patients are not consented 
for recordings 
3.0 
3/24/20 
Added language to allow for 
intervention sessions to be 
conducted remotely via an IRB 
approved video platform or by 
phone if an in-person visit is not 
possible 
Change made in response to 
Temporary UNC Policy on 
Human Subjects-Related 
Research Visits at UNC-
Chapel Hill during COVID-19 
Outbreak 
4.0 
5/12/20 
Added language to further explain 
data being shared with Virginia 
Tech, which includes video 
recordings and that participant 
faces will be blurred prior to 
sending. 
Change made in response to 
New Safety Information (NSI) 
submission to IRB   
5.0 
5/20/20 
Personnel change 
Changes made in response 
to Daniel Del Gaizo, MD no 
longer on the project 
personnel listing as a Co-
Investigator for this study; 
Christopher Olcott, MD 
added to the project 
personnel listing as a Co-
Investigator 
6.0  
11/20/20 
Included language to state we 
may conduct a briefer set of 
measures focused on the primary 
functional assessments and not 
conduct the balance tests 
Change made to shorten 
duration of in-person visits 
due to COVID-19 safety 
precautions 
 
 
Included language to state we will 
email or mail the consent and 
HIPAA forms for the potential 
participant to review before the 
baseline visit 
Change made to shorten 
duration of baseline visit due 
to COVID-19 safety 
precautions 
 
 
Video recordings shared with VA 
Tech will include full PHI (i.e. 
facial images)  
Amendment made to the 
subaward to include 
disclosure of full PHI 
7.0 
3/23/21 
Added language to allow study to 
recruit patients from non-UNC 
Healthcare clinics  
Change made to assist with 
recruitment efforts 
8.0 
10/12/21  
Added additional exclusion 
criteria  
Change made to eliminate 
need for the study to 
withdraw patients who may 
have joint replacement 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
36 
Protocol v11.0 - 20221006  
surgery scheduled in next 6 
months and which it would 
make them unsafe to 
continue participating 
9.0 
1/5/22 
Updated and removed language 
related to video camera data 
capture 
Video camera data collection 
was discontinued 
10.0 
2/21/22 
 
Updated language to state we will 
conduct a limited set of balance 
tests 
Balance tests were paused 
due to COVID restrictions 
and now introducing a limited 
set of tests to conduct 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
37 
Protocol v11.0 - 20221006  
 
 
REFERENCES 
 
1. 
Fingar K, Stocks C, Weiss A, Steiner C. Most Frequent Operating Room Procedures Performed in U.S. 
Hospitals, 2003-2012.  HCUP Statistical Brief #186. 2014. http://www.hcup-
us.ahrq.gov/reports/statbriefs/sb186-Operating-Room-Procedures-United-States-2012.pdf. . 
2. 
Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee 
arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007;89(4):780-785. 
3. 
McMahon M, Block JA. The risk of contralateral total knee arthroplasty after knee replacement for 
osteoarthritis. J Rheumatol. 2003;30(8):1822-1824. 
4. 
Ritter M, Mamlin LA, Melfi CA, Katz BP, Freund DA, Arthur DS. Outcome implications for the timing of 
bilateral total knee arthroplasties. Clinical Orthopaedics & Related Research. 1997(345):99-105. 
5. 
Paxton RJ, Melanson EL, Stevens-Lapsley JE, Christiansen CL. Physcial activity after total knee 
arthroplasty: a critical review. World Journal of Orthopedics. 2015;6(8):614-622. 
6. 
Hammett T, Simonian A, Austin M, et al. Changes in physical activity after total hip or knee arthroplasty: 
A systematic review and meta-analysis of 6 and 12 month outcomes. Arthritis Care Res (Hoboken). 
2017. 
7. 
U.S. Department of Health and Human Services. 2008 Physical Activity Guidelines for Americans. 
Washington, DC2008. 
8. 
Kersten RF, Stevens M, van Raay JJ, Bulstra SK, van den Akker-Scheek I. Habitual physical activity 
after total knee replacement. Phys Ther. 2012;92(9):1109-1116. 
9. 
Arnold JB, Walters JL, Ferrar KE. Does Physical Activity Increase After Total Hip or Knee Arthroplasty 
for Osteoarthritis? A Systematic Review. J Orthop Sports Phys Ther. 2016;46(6):431-442. 
10. 
de Groot IB, Bussmann HJ, Stam HJ, Verhaar JA. Small increase of actual physical activity 6 months 
after total hip or knee arthroplasty. Clin Orthop Relat Res. 2008;466(9):2201-2208. 
11. 
Brandes M, Ringling M, Winter C, Hillmann A, Rosenbaum D. Changes in physical activity and health-
related quality of life during the first year after total knee arthroplasty. Arthritis Care Res (Hoboken). 
2011;63(3):328-334. 
12. 
Harding P, Holland AE, Delany C, Hinman RS. Do activity levels increase after total hip and knee 
arthroplasty? Clin Orthop Relat Res. 2014;472(5):1502-1511. 
13. 
Vissers MM, de Groot IB, Reijman M, Bussmann JB, Stam HJ, Verhaar JA. Functional capacity and 
actual daily activity do not contribute to patient satisfaction after total knee arthroplasty. BMC 
Musculoskelet Disord. 2010;11:121. 
14. 
Walker DJ, Heslop PS, Chandler C, Pinder IM. Measured ambulation and self-reported health status 
following total joint replacement for the osteoarthritic knee. Rheumatology (Oxford). 2002;41(7):755-
758. 
15. 
Zeni JA, Jr., Snyder-Mackler L. Most patients gain weight in the 2 years after total knee arthroplasty: 
comparison to a healthy control group. Osteoarthritis Cartilage. 2010;18(4):510-514. 
16. 
Pellegrini CA, Song J, Semanik PA, et al. Patients Less Likely to Lose Weight Following a Knee 
Replacement: Results From the Osteoarthritis Initiative. J Clin Rheumatol. 2017. 
17. 
Meier W, Mizner RL, Marcus RL, Dibble LE, Peters C, Lastayo PC. Total knee arthroplasty: muscle 
impairments, functional limitations, and recommended rehabilitation approaches. J Orthop Sports Phys 
Ther. 2008;38(5):246-256. 
18. 
Piva SR, Gil AB, Almeida GJ, DiGioia AM, 3rd, Levison TJ, Fitzgerald GK. A balance exercise program 
appears to improve function for patients with total knee arthroplasty: a randomized clinical trial. Phys 
Ther. 2010;90(6):880-894. 
19. 
Alnahdi AH, Zeni JA, Snyder-Mackler L. Gait after unilateral total knee arthroplasty: frontal plane 
analysis. J Orthop Res. 2011;29(5):647-652. 
20. 
Mandeville D, Osternig LR, Chou LS. The effect of total knee replacement on dynamic support of the 
body during walking and stair ascent. Clin Biomech (Bristol, Avon). 2007;22(7):787-794. 
21. 
Westby MD, Brittain A, Backman CL. Expert consensus on best practices for post-acute rehabilitation 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
38 
Protocol v11.0 - 20221006  
after total hip and knee arthroplasty: a Canada and United States Delphi study. Arthritis Care Res 
(Hoboken). 2014;66(3):411-423. 
22. 
Oatis CA. Exercise After Total Knee Arthroplatsy:  Progressive Resistance.  How "Progressive" Are 
We?  What Phyiscal Therapy Records Show. Paper presented at: American College of 
Rheumatology2014; San Francisco, CA. 
23. 
Jones CA, Martin RS, Westby MD, Beaupre LA. Total joint arthroplasty: practice variation of 
physiotherapy across the continuum of care in Alberta. BMC Health Serv Res. 2016;16(1):627. 
24. 
Bruun-Olsen V, Heiberg KE, Wahl AK, Mengshoel AM. The immediate and long-term effects of a 
walking-skill program compared to usual physiotherapy care in patients who have undergone total knee 
arthroplasty (TKA): a randomized controlled trial. Disabil Rehabil. 2013;35(23):2008-2015. 
25. 
Boehler CE, Milton KE, Bull FC, Fox-Rushby JA. The cost of changing physical activity behaviour: 
evidence from a "physical activity pathway" in the primary care setting. BMC Public Health. 
2011;11:370. 
26. 
Bull FC, Milton KE. A process evaluation of a "physical activity pathway" in the primary care setting. 
BMC Public Health. 2010;10:463. 
27. 
Barrett EM, Hussey J, Darker CD. Feasibility of a physical activity pathway for Irish primary care 
physiotherapy services. Physiotherapy. 2016. 
28. 
AuYoung M, Linke SE, Pagoto S, et al. Integrating Physical Activity in Primary Care Practice. Am J 
Med. 2016. 
29. 
Sallis JF, Cervero RB, Ascher W, Henderson KA, Kraft MK, Kerr J. An ecological approach to creating 
active living communities. Annu Rev Public Health. 2006;27:297-322. 
30. 
Gilbert AL, Lee J, Ehrlich-Jones L, et al. A randomized trial of a motivational interviewing intervention to 
increase lifestyle physical activity and improve self-reported function in adults with arthritis Semin 
Arthritis Rheum. 2017;In Press. 
31. 
Liao CD, Lin LF, Huang YC, Huang SW, Chou LC, Liou TH. Functional outcomes of outpatient balance 
training following total knee replacement in patients with knee osteoarthritis: a randomized controlled 
trial. Clin Rehabil. 2015;29(9):855-867. 
32. 
Liao CD, Liou TH, Huang YY, Huang YC. Effects of balance training on functional outcome after total 
knee replacement in patients with knee osteoarthritis: a randomized controlled trial. Clin Rehabil. 
2013;27(8):697-709. 
33. 
Jogi P, Overend TJ, Spaulding SJ, Zecevic A, Kramer JF. Effectiveness of balance exercises in the 
acute post-operative phase following total hip and knee arthroplasty: A randomized clinical trial. SAGE 
Open Med. 2015;3:2050312115570769. 
34. 
Zeni J, Jr., Abujaber S, Flowers P, Pozzi F, Snyder-Mackler L. Biofeedback to promote movement 
symmetry after total knee arthroplasty: a feasibility study. J Orthop Sports Phys Ther. 2013;43(10):715-
726. 
35. 
Levinger P, Zeina D, Teshome AK, Skinner E, Begg R, Abbott JH. A real time biofeedback using Kinect 
and Wii to improve gait for post-total knee replacement rehabilitation: a case study report. Disabil 
Rehabil Assist Technol. 2016;11(3):251-262. 
36. 
Christiansen CL, Bade MJ, Davidson BS, Dayton MR, Stevens-Lapsley JE. Effects of Weight-Bearing 
Biofeedback Training on Functional Movement Patterns Following Total Knee Arthroplasty: A 
Randomized Controlled Trial. J Orthop Sports Phys Ther. 2015;45(9):647-655. 
37. 
Williams QI, Gunn AH, Beaulieu JE, et al. Physical therapy vs. internet-based exercise training (PATH-
IN) for patients with knee osteoarthritis: study protocol of a randomized controlled trial. BMC 
Musculoskelet Disord. 2015;16:264. 
38. 
Schrubbe LA, Ravyts SG, Benas BC, et al. Pain coping skills training for African Americans with 
osteoarthritis (STAART): study protocol of a randomized controlled trial. BMC Musculoskelet Disord. 
2016;17(1):359. 
39. 
Allen KD, Bongiorni D, Bosworth HB, et al. Group Versus Individual Physical Therapy for Veterans With 
Knee Osteoarthritis: Randomized Clinical Trial. Phys Ther. 2016;96(5):597-608. 
40. 
Allen KD, Oddone EZ, Coffman CJ, et al. Telephone-based self-management of osteoarthritis: a 
randomized, controlled trial. Annals of Internal Medicine. 2010;153:570-579. 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
39 
Protocol v11.0 - 20221006  
41. 
Allen KD, Oddone EZ, Coffman CJ, et al. Patient, Provider, and Combined Interventions for Managing 
Osteoarthritis in Primary Care: A Cluster Randomized Trial. Ann Intern Med. 2017. 
42. 
Allen KD, Yancy WS, Jr., Bosworth HB, et al. A Combined Patient and Provider Intervention for 
Management of Osteoarthritis in Veterans: A Randomized Clinical Trial. Ann Intern Med. 
2016;164(2):73-83. 
43. 
Allen KD, Sanders LL, Olsen MK, et al. Internet Versus DVD Decision Aids for Hip and Knee 
Osteoarthritis. Musculoskeletal Care. 2016;14(2):87-97. 
44. 
Queen RM, Attarian DE, Bolognesi MP, Butler RJ. Bilateral symmetry in lower extremity mechanics 
during stair ascent and descent following a total hip arthroplasty: a one-year longitudinal study. Clin 
Biomech (Bristol, Avon). 2015;30(1):53-58. 
45. 
Butler RJ, Ruberte Thiele RA, Barnes CL, Bolognesi MP, Queen RM. Unipedal balance is affected by 
lower extremity joint arthroplasty procedure 1 year following surgery. J Arthroplasty. 2015;30(2):286-
289. 
46. 
Queen RM, Butler RJ, Adams SB, Jr., DeOrio JK, Easley ME, Nunley JA. Bilateral differences in gait 
mechanics following total ankle replacement: a two year longitudinal study. Clin Biomech (Bristol, 
Avon). 2014;29(4):418-422. 
47. 
Queen RM, Appleton JS, Butler RJ, et al. Total hip arthroplasty surgical approach does not alter 
postoperative gait mechanics one year after surgery. PM R. 2014;6(3):221-226; quiz 226. 
48. 
Queen RM, Sparling TL, Butler RJ, et al. Patient-Reported Outcomes, Function, and Gait Mechanics 
After Fixed and Mobile-Bearing Total Ankle Replacement. J Bone Joint Surg Am. 2014;96(12):987-993. 
49. 
Somers TJ, Blumenthal JA, Guilak F, et al. Pain coping skills training and lifestyle behavioral weight 
management in patients with knee osteoarthritis: a randomized controlled study. Pain. 
2012;153(6):1199-1209. 
50. 
Queen RM, De Biassio JC, Butler RJ, DeOrio JK, Easley ME, Nunley JA. J. Leonard Goldner Award 
2011: changes in pain, function, and gait mechanics two years following total ankle arthroplasty 
performed with two modern fixed-bearing prostheses. Foot Ankle Int. 2012;33(7):535-542. 
51. 
Queen RM, Butler RJ, Watters TS, Kelley SS, Attarian DE, Bolognesi MP. The effect of total hip 
arthroplasty surgical approach on post-operative gait mechanics. Journal of Arthroplasty. 2011;26 (6 
Suppl):66-71. 
52. 
Queen RM, Watters TS, Abbey AN, Sabesan VJ, Vail TP, Bolognesi MP. Gait symmetry: a comparison 
of hip resurfacing and jumbo head total hip arthroplasty patients. J Arthroplasty. 2011;26(5):680-685. 
53. 
Sims EL, Keefe FJ, Kraus VB, Guilak F, Queen RM, Schmitt D. Racial differences in gait mechanics 
associated with knee ostoarthritis. Aging Clinical and Experimental Research. 2009;21(6):463-469. 
54. 
Queen RM, Watters TS, Abbey AN, Sabesan VJ, Vail TP, Bolognesi MP. Gait symmetry: a comparison 
of hip resurfacing and jumbo head total hip arthroplasty patients. J Arthroplasty.26(5):680-685. 
55. 
Nelson AE, Golightly YM, Renner JB, et al. Variations in Hip Shape Are Associated with Radiographic 
Knee Osteoarthritis: Cross-sectional and Longitudinal Analyses of the Johnston County Osteoarthritis 
Project. J Rheumatol. 2016;43(2):405-410. 
56. 
An H, Marron JS, Schwartz TA, et al. Novel statistical methodology reveals that hip shape is associated 
with incident radiographic hip osteoarthritis among African American women. Osteoarthritis Cartilage. 
2016;24(4):640-646. 
57. 
Barbour KE, Hootman JM, Helmick CG, et al. Meeting physical activity guidelines and the risk of 
incident knee osteoarthritis: a population-based prospective cohort study. Arthritis Care Res (Hoboken). 
2014;66(1):139-146. 
58. 
Broderick JE, Keefe FJ, Bruckenthal P, et al. Nurse practitioners can effectively deliver pain coping 
skills training to osteoarthritis patients with chronic pain: A randomized, controlled trial. Pain. 
2014;155(9):1743-1754. 
59. 
Callahan LF, Cleveland RJ, Shreffler J, et al. Evaluation of active living every day in adults with arthritis. 
J Phys Act Health. 2014;11(2):285-295. 
60. 
Koch GG, Schwartz TA. An overview of statistical planning to address subgroups in confirmatory 
clinical trials. J Biopharm Stat. 2014;24(1):72-93. 
61. 
Cleveland RJ, Schwartz TA, Prizer LP, et al. Associations of educational attainment, occupation, and 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
40 
Protocol v11.0 - 20221006  
community poverty with hip osteoarthritis. Arthritis Care Res (Hoboken). 2013;65(6):954-961. 
62. 
Allen KD, Chen JC, Callahan LF, et al. Racial differences in knee osteoarthritis pain: potential 
contribution of occupational and household tasks. J Rheumatol. 2012;39(2):337-344. 
63. 
Callahan LF, Shreffler JH, Altpeter M, et al. Evaluation of group and self-directed formats of the Arthritis 
Foundation's Walk With Ease Program. Arthritis Care Res (Hoboken). 2011;63(8):1098-1107. 
64. 
Allen KD, Helmick CG, Schwartz TA, DeVellis B, Renner JB, Jordan JM. Racial differences in self-
reported pain and function among individuals with radiographic hip and knee osteoarthritis: The 
Johnston County Osteoarthritis Project. Osteoarthritis & Cartilage. 2009;17(9):1132-1136. 
65. 
Jordan JM, Helmick CG, Renner JB, et al. Prevalence of knee symptoms and radiographic and 
symptomatic knee osteoarthritis in African Americans and Caucasians: the Johnston County 
Osteoarthritis Project. The Journal of Rheumatology. 2007;31(4):172-180. 
66. 
Goeppinger J, Armstrong B, Schwartz T, Ensley D, Brady TJ. Self-managment education for persons 
with arthritis: managing comorbidity and eliminating health disparities. Arthritis Care and Research. 
2007;57(6):1081-1088. 
67. 
Evenson KR, Wen F, Hales D, Herring AH. National youth sedentary behavior and physical activity 
daily patterns using latent class analysis applied to accelerometry. Int J Behav Nutr Phys Act. 
2016;13:55. 
68. 
Hales D, Vaughn AE, Mazzucca S, et al. Development of HomeSTEAD's physical activity and screen 
time physical environment inventory. Int J Behav Nutr Phys Act. 2013;10:132. 
69. 
Miller WR, Rollnick S. Motivational Interviewing: Preparing People for Change, 2nd Ed. New York: 
Guilford Press; 2002. 
70. 
O'Halloran PD, Blackstock F, Shields N, et al. Motivational interviewing to increase physical activity in 
people with chronic health conditions: a systematic review and meta-analysis. Clin Rehabil. 
2014;28(12):1159-1171. 
71. 
Rubak S, Sandbaek A, Lauritzen T, Christensen B. Motivational interviewing: a systematic review and 
meta-analysis. British Journal of General Practice. 2005;55:305-312. 
72. 
Semanik PA, Lee J, Song J, et al. Accelerometer-monitored sedentary behavior and observed physical 
function loss. Am J Public Health. 2015;105(3):560-566. 
73. 
White DK, Tudor-Locke C, Zhang Y, et al. Daily walking and the risk of incident functional limitation in 
knee osteoarthritis: an observational study. Arthritis Care Res (Hoboken). 2014;66(9):1328-1336. 
74. 
Carr LJ, Mahar MT. Accuracy of intensity and inclinometer output of three activity monitors for 
identification of sedentary behavior and light-intensity activity. J Obes. 2012;2012:460271. 
75. 
Troiano RP, Berrigan D, Dodd KW, Masse LC, Tilert T, McDowell M. Physical activity in the United 
States measured by accelerometer. Medicine and Science in Sports and Exercise. 2008;40(181-188). 
76. 
Choi L, Ward SC, Schnelle JF, Buchowski MS. Assessment of wear/nonwear time classification 
algorithms for triaxial accelerometer. Med Sci Sports Exerc. 2012;44(10):2009-2016. 
77. 
Matthews CE. Calibration of accelerometer output for adults. Med Sci Sports Exerc. 2005;37(11 
Suppl):S512-522. 
78. 
Ward DS, Rodgers AB. Objective monitoring of physical activity: closing the gaps in the science of 
accelerometry. Medicine and Science in Sports and Exercise. 2005;37(11):S582-588. 
79. 
Price C, Parker D, Nester C. Validity and repeatability of three in-shoe pressure measurement systems. 
Gait Posture. 2016;46:69-74. 
80. 
Unver B, Baris RH, Yuksel E, Cekmece S, Kalkan S, Karatosun V. Reliability of 4-meter and 10-meter 
walk tests after lower extremity surgery. Disabil Rehabil. 2016:1-5. 
81. 
Ageberg E, Roos HP, Silbernagel KG, Thomee R, Roos EM. Knee extension and flexion muscle power 
after anterior cruciate ligament reconstruction with patellar tendon graft or hamstring tendons graft: a 
cross-sectional comparison 3 years post surgery. Knee Surg Sports Traumatol Arthrosc. 
2009;17(2):162-169. 
82. 
Adams D, Logerstedt DS, Hunter-Giordano A, Axe MJ, Snyder-Mackler L. Current concepts for anterior 
cruciate ligament reconstruction: a criterion-based rehabilitation progression. J Orthop Sports Phys 
Ther. 2012;42(7):601-614. 
83. 
Barber SD, Noyes FR, Mangine RE, McCloskey JW, Hartman W. Quantitative assessment of functional 

Improving Physical Activity and Gait Symmetry after Total Knee Arthroplasty 
Version 11.0 
Protocol #19-0568 
 
6 October 2022 
41 
Protocol v11.0 - 20221006  
limitations in normal and anterior cruciate ligament-deficient knees. Clin Orthop Relat Res. 
1990(255):204-214. 
84. 
Rohman E, Steubs JT, Tompkins M. Changes in involved and uninvolved limb function during 
rehabilitation after anterior cruciate ligament reconstruction: implications for Limb Symmetry Index 
measures. Am J Sports Med. 2015;43(6):1391-1398. 
85. 
Stewart AL, Mills KM, King AC, Haskell WL, Gillis D, RItter PL. CHAMPS physical activity questionnaire 
for older adults: outcomes for interventions. Medicine and Science in Sports and Exercise. 
2001;33(7):1126-1141. 
86. 
Dobson F, Hinman RS, Roos EM, et al. OARSI recommended performance-based tests to assess 
physical function in people diagnosed with hip or knee osteoarthritis. Osteoarthritis Cartilage. 
2013;21(8):1042-1052. 
87. 
Berg K, Maki B, Williams JI, Holliday P, Wood-Dauphinee S. A comparison of clinical and laboratory 
measures of postural balance in an elderly population. Archives of Physical Medicine & Rehabilitation. 
1992;73:1073-1083. 
88. 
Chan AC, Pang MY. Assessing Balance Function in Patients With Total Knee Arthroplasty. Phys Ther. 
2015;95(10):1397-1407. 
89. 
Horak FB, Wrisley DM, Frank J. The Balance Evaluation Systems Test (BESTest) to differentiate 
balance deficits. Phys Ther. 2009;89(5):484-498. 
90. 
Roos EM, Toksvig-Larsen S. Knee injury and Osteoarthritis Outcome Score (KOOS) - validation and 
comparison to the WOMAC in total knee replacement. Health Qual Life Outcomes. 2003;1:17. 
91. 
Brown ML, Plate JF, Von Thaer S, et al. Decreased Range of Motion After Total Knee Arthroplasty Is 
Predicted by the Tampa Scale of Kinesiophobia. J Arthroplasty. 2016;31(4):793-797. 
92. 
Dominick GM, Zeni JA, White DK. Association of Psychosocial Factors With Physical Activity and 
Function After Total Knee Replacement: An Exploratory Study. Arch Phys Med Rehabil. 2016;97(9 
Suppl):S218-225. 
93. 
Miller RP, Kori SH, Todd DD. The Tampa Scale. Tampa, FL1991. 
94. 
Allen KD, Arbeeva L, Callahan LF, et al. Physical therapy vs internet-based exercise training for 
patients with knee osteoarthritis: results of a randomized controlled trial. Osteoarthritis Cartilage. 
2018;26(3):383-396. 
95. 
Lewis CC, Weiner BJ, Stanick C, Fischer SM. Advancing implementation science through measure 
development and evaluation: a study protocol. Implement Sci. 2015;10:102. 
96. 
Weiner BJ, Dorsey C, Stanick CF, Halko HM, Powell BJ, Lewis CC. Psychometric assessment of three 
newly developed implemenation outcome measures. 9th Annual Conferene on the Science of 
Dissemination and Implementation; 2016; Washington, DC. 
97. 
Sangha O, Stucki G, Liang MH, Fossel AH, Katz JN. The self-administered comorbidity questionnaire: 
a new method to assess comorbidity for clinical and health services research. Arthritis & Rheumatism. 
2003;49(2):156-163.