Reducing Sedentary Time Using an Innovative mHealth Intervention Among Total Knee Replacement Patients
Phase: NA
Conditions: Knee Arthroplasty
Sponsor: University of South Carolina

University of South Carolina Study Protocol v.7 
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Study Title: Technology Interventions to Improve Outcomes After Knee Replacement 
 
Grant Title: Reducing Sedentary Time using an Innovative mHealth Intervention among Total 
Knee Replacement Patients 
 
Principal Investigator Name: Christine Pellegrini, PhD  
 
Statement of Compliance: This trial will be conducted in compliance with the protocol, 
International Council for Harmonization/Good Clinical Practice requirements (ICH/GCP), and 
applicable state, local and federal regulatory requirements  
 
NCT: NCT04482400 
 
Version Date: June 14, 2023 
 
 
 

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A. SPECIFIC AIMS  
The objective of this study is to expand our previous and current work by examining an innovative, just-
in-time mHealth sedentary behavior intervention for TKA patients. The specific aims of the project are: 
Aim 1: To examine the effects of the NEAT!2 mHealth sedentary reduction intervention on 
sedentary time in TKR patients at the end of treatment (2 months) and following a maintenance 
period (5 months). 
Aim 2: To evaluate changes in total physical activity time (light, moderate, and vigorous), physical 
function, and pain in TKR patients after participating in the NEAT!2 mHealth sedentary reduction 
intervention at the end of treatment (2 months) and following a maintenance period (5 months).   
Aim 3: To examine the dose-response relationship between adherence to NEAT!2 and changes in 
sedentary time, total physical activity time, physical function, and pain. Measures of adherence 
include the percentage of calls completed/total possible (5 calls), days of app use/total days (56 
days), and number of activity transitions following NEAT!2 prompt/total number of NEAT!2 prompts. 
B. BACKGROUND AND SIGNIFICANCE 
Adults with TKR are an important population, accounting for over $13 billion/year in US healthcare 
costs.1–3 More than 675,000 adults undergo TKR annually.4 TKR results in significant improvements in 
physical function and pain among the majority of patients,5,6 yet these improvements do not translate to 
increases in physical activity. Most TKR patients fail to increase physical activity above pre-operative 
levels after surgery, with >90% remaining below federal physical activity recommendations two years 
after TKR. 7–10   
Physical activity interventions for TKR patients have shown success, but the increases in activity 
were modest compared to changes in the general population.11,12 After TKR, we found patients face 
additional barriers to activity, including continued pain, physical limitations, and a lack of motivation to 
be active.13 As a result, patients continue to spend >60% of the day in sedentary behaviors after 
surgery, which is similar to adults with knee osteoarthritis.14,15 This is concerning because among those 
with knee osteoarthritis, excess sedentary behavior is strongly associated with functional declines,15,16 
physical frailty,17 and disability.18 Sustained high levels of sedentary behavior after TKR may lead to 
impaired long-term function and undermine the overall success of the surgical treatment. Intervening to 
reduce sedentary behavior may be a more feasible, first step approach for TKR patients who may not 
yet be ready to increase activity.  
This study leverages TKR as a teachable moment19 to implement an innovative strategy to 
decrease sedentary behavior using a mobile health (mHealth) just-in-time intervention. NEAT!2 (Non-
Exercise Activity Thermogenesis version 2) builds on our NEAT! study.20 Our NEAT! app successfully 
interrupted prolonged bouts of sitting, decreased sedentary time by 8.1±4.5% (45.7 min/day), and 
increased light activity by 7.9±5.5% in adults with type 2 diabetes.20 The NEAT!2 app was updated and 
adapted with TKR patient input and preferences. 
To our knowledge, no prior studies have examined a sedentary reduction intervention specifically 
designed for TKR patients after surgery. The expected outcome from this study includes determining if 
an mHealth sedentary reduction intervention is an effective approach to decrease sedentary time in 
patients after TKR. The results of this study will build on our previous and current work to improve 
health behaviors after TKA. Specifically, we expect to identify potentially effective and scalable 
strategies to help TKR patients become more physically active following surgery and ultimately lead to 
improved long-term functional outcomes.  
 
C. PRELIMINARY STUDIES 
Our Steps to Health study21 recruited 401 adults with arthritis (56.3 years, 86% women, 64% white) in 
Columbia, SC to a 12-week exercise program. Retention at 12 weeks and 9 months was 80% and 74%, 
respectively. For our Patient-Centered Weight Loss (PACE) pilot study, 16 patients (63.3±7.5 years, 
BMI 36.5 ± 5.1 kg/m2) scheduled for TKR were randomized to start a 14-week weight loss program 
either before (PACE) or after surgery (Delayed PACE). Retention at 26 weeks was 76%. To minimize 

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attrition in the proposed study, we will randomize after TKR, since 60% of drop-outs in the previous 
study occurred prior to surgery 
Nine adults (53.1±10.7 years, BMI 37.4±9.9kg/m2) with diabetes used the NEAT! app on 21.9±8.0 
days/month. NEAT! interrupted continuous bouts (≥20 minutes) of sitting by providing prompts to 
engage in light-intensity activity for ≥2 minutes. Prompts to interrupt sedentary time were given 5.8±3.5 
times/day. Participants reduced their sedentary time by 8.1±4.5% (45.7 min/day) between baseline and 
1 month,20 and is above our definition of a clinical meaningfulness of change (i.e., -5%; -30 min/day). 
Nearly 88% of participants indicated they would use NEAT! again in the future, suggesting high 
acceptability of NEAT!. 
The research team has experience with recruitment of TKR patients in the Columbia, SC area and 
specifically with Prisma Health Orthopedic Center. Currently, we have recruited 26 patients who 
underwent a TKR to participate in an ongoing study examining a physical therapist led physical activity 
intervention on objectively measured physical activity levels (USC ASPIRE-I funded – PRO00081254).  
To date, 20 participants have completed the 12-week assessment.  
D. RESEARCH DESIGN AND METHODS AND DATA ANALYSIS  
 
Study Design: This study is a randomized controlled trial examining effects of the NEAT!2 mHealth 
sedentary reduction intervention on sedentary time in TKR patients at the end of treatment (2 
months) and following a maintenance period (5 months).  Subject participation will last 
approximately 6 months. The project timeline is displayed in Figure 1, which highlights study 
procedures, enrollment, data collection and data analysis over the grant period.  Figure 2 displays 
the study design.  
 
Figure 1. Updated Study Timeline 
 
Figure 2. Updated Study Design 

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Procedures: 
a) Recruitment: The study will 
recruit and identify patients within 
one year of their total knee 
replacement. See Section E2 
below for more details on 
recruitment. 
b) Screening: Participants may 
be screened online (via 
REDCap), via telephone, or in-
person, based on preference and 
recruitment method, to assess 
the study’s inclusion and 
exclusion criteria. Eligible candidates who completed the online screener will be contacted by 
telephone, to further discuss the study, and answer questions. Eligible candidates will be mailed or 
emailed the consent document to read prior to the visit. 
c) Informed Consent: A study member will go through the informed consent process prior to starting 
the baseline assessment. During the informed consent process, study staff will discuss full details of 
the study, risks/benefits, and answer any questions they may have. Interested participants and staff 
will only sign the consent after going through all details of the study and confirming they have read 
the consent document. After signing the informed consent form, participants will be provided a 
copy. 
d) Baseline Assessment: The baseline assessment will be completed at either the University of 
South Carolina or Prisma Health Orthopedics. During the assessment, participants will be asked to 
complete three physical function tests and will be provided with the two activity monitors to wear for 
7 days (procedures for these measures are described below). We anticipate this will take 
approximately 20 minutes. Participants will also be provided with paper surveys or a link to 
complete the surveys online. It is anticipated that it will take approximately 10 minutes to complete 
the surveys. Following the 7-day wear period, participants will return the monitors via mail with a 
prepaid stamped envelope.   
In addition, to ensure compatibility and eliminate the potential of technological issues, 
participants with an iPhone will download both the MyKneeGuide (https://www.mykneeguide.com) 
and NEAT!2 apps on their phone. All participants will be able to use the MyKneeGuide app prior to 
randomization; however, the NEAT!2 app will remain idle. Participants will not receive notifications 
about sedentary time until after randomization. In the event the participant does not have an 
iPhone, they will be asked to use MyKneeGuide on the website since the app is not compatible with 
Androids. The NEAT!2 app is compatible with both Android and iOS platforms.  
e) Randomization:  A study staff member will call the participant once all baseline assessment items 
have been completed. In addition to reminding participants of the study details, an equipoise 
induction will be conducted to review the benefits and barriers to both general research study 
participation and specific study participation.21 Study staff will have the participant discuss the pros 
and cons of the study randomized conditions (NEAT!2 and Tech Ed [control]) and staff will review 
the importance of a control group and how attrition bias can alter the results. The equipoise 
induction will be done to highlight why the research is being conducted, the importance of attending 
assessments, regardless of adherence to the intervention, and to help prevent differential attrition. 
Participants who express continued interest in participating will be randomized (stratified by age, 

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<65 years and ≥65 years) on a rolling basis using randomly permuted blocks to one of two 
conditions: (1) NEAT!2, or (2) Tech Ed (Control). 
f) Randomized Conditions: 
NEAT!2. Participants randomized to NEAT!2 will have their NEAT!2 
app turned on  after randomization. The NEAT!2 app, designed to 
target automatic processes, works by promoting awareness of 
prolonged sedentary behavior. NEAT!2 uses the internal 
accelerometer and Android OR iOS activity recognition libraries to 
classify the smartphone’s patterns of movement. When 30 minutes of 
continuous sedentary time are detected using machine learning 
algorithms, the NEAT!2 app triggers an audible tone/vibration and 
places a notification on the phone’s lock/home screen (see Figure 3). 
When the app detects movement of a predefined magnitude and 
threshold (e.g., using the phone while seated would be below the 
threshold, whereas walking with the phone would be above the 
threshold), the 30-minute timer will restart; thus, the app will only 
provide notifications when prolonged bouts of minimal to no movement 
are objectively detected. Reminders will only occur during waking 
hours and each notification will consist of a different message. 
Participants will be asked to use the app until 3 months after randomization.     
NEAT!2 participants will be given an initial goal to reduce sedentary time by 30 minutes/day, 
ultimately progressing to a 90 minute/day reduction by 2 months after randomization. To assist with 
goal attainment and target controlled processes, participants will receive biweekly coaching calls for 
the first 2 months. Coaching calls will be completed by trained coaches, be semi-scripted, and last 
~10-15 minutes. During calls, coaches will use motivational interviewing, discuss goal progression 
and educational handouts, problem solve, and set a SMART (specific, measurable, attainable, 
realistic/reward, timely) goal related to reducing sedentary time. All calls will be recorded and timed 
to assess treatment fidelity. After the 2-month assessment, participants will have the option to 
continue using the app until 5 months. Additionally, participants will receive monthly calls between 2 
and 5 months, unrelated to the intervention and focused on surgery recovery, to maintain contact 
and help with retention during follow-up. The maintenance calls are expected to last approximately 
~5 minutes.  
Tech Ed (Control). Participants randomized to Control will receive an attention-matched education 
program. Control participants will be asked to continue using the control app or website 
(MyKneeGuide) until 2 months after randomization. MyKneeGuide is a commercially-available 
app/website and provides pre- and post-operative information for TKR patients, tracks 
appointments, connects to local rehabilitation facilities, and can connect with other patients who 
have recently had TKR. Control participants also will receive biweekly calls for the first 2 months.  
During calls, study staff will discuss surgery recovery (e.g., range of motion, sleep, stretching, 
reducing risk of injury, and emotional self-care) and avoid topics relating to sedentary behavior and 
physical activity. All calls will last approximately 10-15 minutes and will be recorded to evaluate 
whether any unintended content was discussed (e.g., reducing sedentary time, physical activity). 
Control participants will receive similar monthly calls between 2-5 months. Following the 5-month 
assessment, participants in Control will be offered the NEAT!2 app. 
g) Treatment Fidelity: Telephone sessions will be audiotaped, and a 15% sample rated for treatment 
fidelity on a quarterly basis. If fidelity falls <80%, coaches will be retrained. Fidelity checklists will 
assess SMART goal setting, intended session content (e.g., sedentary behavior goals for NEAT!2 
or stiffness for Control) and unintended session content (i.e., discussing physical activity or 
sedentary behavior with Control participants). Drs. Pellegrini and Wilcox will train the coaches on 

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intervention procedures and the project coordinator will serve as primary fidelity evaluator. Coaches 
will meet every other week with Drs. Pellegrini and Wilcox to review treatment delivery. 
h) Follow-Up Assessments: In addition to the baseline assessment, assessments will be completed 
at 2 months (end of treatment) and 5 months (maintenance). The 2 and 5 month assessments will 
be at either the University of South Carolina TecHealth Center (915 Greene Street, Columbia, SC), 
Prevention Research Center (921 Assembly St, Columbia, SC) or Prisma Health Orthopedics.  
Detailed descriptions and a timeline of outcomes are provided below in the text and Table 1. Briefly, 
at all three assessments, participants will be asked to complete surveys (demographics, brief 
medical history, KOOS, WOMAC) which should take approximately 10 minutes to complete. Based 
on participant preferences, surveys will be able to be completed on paper or online via REDCap. 
Participants will also be asked to wear an Actigraph Link accelerometer and an ActivPAL for 7 days 
at each assessment. At the end of the 7 days these monitors will be dropped off or mailed in a 
prepaid envelope to the University of South Carolina TecHealth Center.  In addition to the surveys 
and monitor, at each assessment participants will complete functional tests which will take 
approximately 20 minutes to complete. Participants will receive $15 completing the 2 and 5 month 
assessments ($30 total). 
 
Table 1. Study Outcomes and Measures 
Concept 
Variable 
Measure 
Data Collection 
Aim 1 Outcome 
Sedentary 
Behavior  
 
 
Domain Specific 
Sedentary 
Behavior 
(exploratory) 
- Objectively measured 
sedentary behavior 
 
 
- Self-report sedentary 
behavior 
-Minutes and % of daily sedentary 
time22,23 
 
 
-SIT-Q24 
- ActiGraph GT9X Link 
worn on hip  
- ActivPAL worn on thigh 
 
-RedCap survey 
Aim 2 Outcomes 
Total Physical 
Activity Time 
- Objectively measured 
physical activity 
- Minutes of total activity (light, moderate, 
and vigorous)/week22,23 
- ActiGraph GT9X Link 
worn on hip  
- ActivPAL worn on thigh 
Physical function  - Objectively measured 
physical function 
- Six-minute walk (feet); chair stands/30 
seconds; timed up and go (seconds) 
using Osteoarthritis Research Society 
International (OARSI) procedures25 
- In-person assessment 
 
Pain  
- Self-reported pain 
- Western Ontario and McMaster 
Universities Arthritis Index (WOMAC)26 
pain scale 
- REDCap survey 
Aim 3 Outcome 
NEAT!2 
Adherence 
- Intervention adherence 
- % of calls completed; days of app use; 
number of activity transitions following 
NEAT!2 prompt 
- NEAT!2 coach interface 
Demographic, Health Status, and Process Variables 
Demographics 
- Age, sex, race, ethnicity, 
marital status, living status, 
education 
- Demographic questionnaire 
- REDCap survey (pre-op 
only) 
Health Status 
- Height, weight, BMI 
- Medical history 
- Stadiometer and electronic scale 
- Brief medical history 
- In-person assessment 
- REDCap survey 
Knee Symptoms 
- Self-reported knee symptoms 
- Knee injury and Osteoarthritis Outcome 
Score (KOOS)27  
- REDCap survey 
Habit formation 
- Habit strength related to 
sitting  
- Adapted Self-Report Habit Index23  
 
- REDCap survey 
Patient-reported 
outcomes 
- Self-reported general health, 
sleep disturbance, and mobility 
- Patient-Reported Outcomes 
Measurement Information System 
(PROMIS).28  
- REDCap survey 
Covid-19 impact  
-Self-reported impacts from the 
COVID-19 pandemic 
-Modified Epidemic-Pandemic Impacts 
Inventory (EPII)29 
-Paper survey 

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Measures 
1. Sedentary behavior (Aim 1) and total physical activity time (Aim 2) will primarily be assessed 
with the ActiGraph GT9X Link (Pensacola, FL).  Participants will be asked to wear the Actigraph 
accelerometer on their hip using a waistband for 7 days during waking hours (except water 
activities).  Following best practice recommendations,30–33 at least four valid days of the  7 days will 
be required to be included in analyses, with a valid day defined as participants wearing the 
accelerometer for at least 10 hours/day.22  Non-wear time is defined as ≥90 minutes with zero 
activity counts, allowing for up to 2 minutes of <100 counts/min.23 Sedentary time for the Actigraph 
is defined as <100 counts/min and total activity as ≥100 counts/min).22 Average daily sedentary time 
(minutes/day), percentage of the waking day spent in sedentary time, and weekly total physical 
activity will be calculated. Data from the Actigraphs will be processed using ActiLife 6 (Pensacola, 
FL). Sedentary time will also be assessed using an ActivPALTM PAL Technologies Ltd, (Glasgow, 
UK) which can better distinguish body position (e.g., sitting and standing). At the same time 
participants are wearing the Actigraph, participants will be asked to wear the ActivPAL on their thigh 
(non-surgery leg) using waterproof tape. They will be asked to wear the monitor for 24 hours/day. 
The time spent sitting/lying, standing, and walking, transitions and step counts will be determined 
using the ActivPAL software. Participants will also complete a 7-day log indicating times either 
device was worn and taken off.   
2. Physical function (Aim 2) measures will include the chair stand, timed up and go, and 6-minute 
walk test. All physical function tests will be completed following Osteoarthritis Research Society 
International (OARSI) recommendation procedures.24 During the chair stand test, patients are 
asked to complete as many chair stand repetitions as possible during a 30-second period. The 
Timed Up and Go Test assesses the time in seconds taken to rise from a chair, walk 3-meters, turn, 
walk back to the chair, and sit down. The Six Minute Walk Test evaluates the maximal distance a 
patient can cover during a 6-minute period. 
3. Pain (Aim 2) and related self-reported outcomes will be assessed using two methods: 1) Knee 
Injury and Osteoarthritis Outcome Score (KOOS) on this participants will self-report on symptoms, 
stiffness, pain, daily function, and active function of their knee from the past week; 2) Western 
Ontario and McMaster Universities Arthritis Index (WOMAC) is a 15-item survey assessing pain and 
stiffness over the last 48-hours on a 5-point Likert scale.25 
 
4. Adherence to NEAT!2 intervention (Aim 3) will be examined by (a) percentage of coaching calls 
completed/total calls prescribed by intervention (5 calls), (b) total days the NEAT!2 app was 
used/total days possible (56 days), and (c) response to NEAT!2 notifications. The response to 
NEAT!2 notifications will be defined as (1) the percentage of notifications in which a transition from 
sitting to standing/walking was detected within 5 minutes of the prompt divided by total number of 
notifications, and (2) average time from notification to activity transition. All NEAT!2 app data will be 
obtained and exported from the NEAT!2 coaching interface. 
5. Demographic, Process, or Exploratory Measures 
a. Weight will be measured at all assessments. Measurements will be taken without shoes, 
wearing light clothing on a calibrated beam balance scale. Height will also be measured 
using a stadiometer, and body mass index (BMI) will be calculated as weight in 
pounds/(height in inches)²) x 704.5. 
b. Patient-reported outcomes will be assessed using Patient-Reported Outcomes 
Measurement Information System (PROMIS).28 PROMIS utilizes a computer adaptive test 
via RedCap.34 We will assess general health, sleep disturbance, and mobility.  

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c. Adapted Self-Report Habit Index23 assesses habit strength related to sitting, stretching, and 
exercising. Participants answer the questions on a 1-7 Likert scale ranging from “Strongly 
Disagree” to “Strongly Agree”. 
d. Sedentary behavior will also be assessed with the SIT-Q.24  This will be assessed as part of 
the web screening to estimate how many hours individuals spent sitting on an average day 
over the last 3 months. The survey assesses time spent sleeping and sitting time during 
multiple domains (e.g., meals, transportation, work, leisure). The survey will also be 
administered at each assessment to explore changes in domain specific sedentary time. 
e. COVID-19 impact will be assessed using a modified version of the Epidemic-Pandemic 
Impacts Inventory (EPII) survey.29 The survey is a tool designed to assess tangible impacts 
of epidemics and pandemics across many domains. The adaptations made to the survey 
were made to provide a shorter version that only assessed COVID-19 related concerns for 
this project. This will be administered at the 2 and 5-month appointments. 
Statistical Analysis: The primary analysis will examine changes in sedentary time (minutes/day, 
percentage/day) between NEAT!2 and Control. Secondary analyses will examine changes in total 
physical activity (daily minutes objectively-measured from ActiGraph accelerometers), physical function 
(walking distance from the 6-minute walk test), and self-reported pain (WOMAC). Due to multiple 
statistical testing for each pre-specified hypothesis, we will adjust for errors and keep the overall 
nominal significance (alpha) level at 0.05. SAS V9.4 (Cary, NC) will be the primary statistical analysis 
program. Multiple linear regression with generalized estimating equation (GEE) methodology 
accounting for follow-up assessments will be used to evaluate whether participants randomized to 
NEAT!2 sedentary reduction intervention had greater improvements in sedentary time, physical activity, 
physical function, and pain than Control at 2- and 5- months. The model will be adjusted for potential 
covariates (i.e., age, sex, BMI, comorbidities). Regression coefficients and corresponding confidence 
intervals (CIs) to compare those in NEAT!2 and Control at 2- and 5-months will be computed for each 
outcome (Aims 1 and 2). For Aim 3, multiple linear regression models will be used to evaluate the 
association between adherence and reductions in sedentary time, higher total physical activity time, 
improved physical function, and less pain accounting for baseline differences and adjusted for potential 
covariates. Regression coefficients and corresponding CIs of adherence will be computed for each 
outcome. Descriptive analyses of baseline demographic and process data will be conducted. 
Sample Size: The sample size of this study was chosen to allow for 40 subjects to receive NEAT!2 
intervention and the same number to serve as the Control (a total of 80). We will recruit 92 subjects into 
the study, expecting that no more than 15% of these subjects will fail to return at 2 or 5 month post-
surgery assessment yielding at least 80 subjects for change from baseline to follow-up assessments. 
To estimate power for Aim 1, we used PACE data where an average of 70.1% of the day was spent in 
sedentary behavior before surgery. We expect to detect an 8.1% reduction in sedentary time in 
participants in NEAT!2 with modest or no reduction in Control. With 40 participants in each group, we 
have 90% power to detect an 8.1% reduction in sedentary time (i.e., effect size of 0.7) between 
participants in NEAT!2 and Control group from baseline and 2- or 5-month assessment. For the 
secondary outcomes in Aim 2, we will have 80% power to detect a minimum detectable effect size of 
0.7 (i.e., 230.6 minutes increase in weekly total physical activity time, 213.5 ft improvement in physical 
function, and 2 point reduction in pain). 
 
Data Management: All surveys will be administered either on paper or online via REDCap (secure, 
web application for building and managing online surveys and database – managed by the University of 
South Carolina). Paper surveys will be stored in a locked filing cabinet in the TecHealth Center at 
University of South Carolina. All computer files will be password protected. Only the study team will 
have access to the data. 
E. PROTECTION OF HUMAN SUBJECTS 
 

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1.  TARGET POPULATION: 
After initial identification of potential participants by surgeons and staff, research staff will send 
recruitment letters and materials via email and mail. Participants can complete the screening online (via 
REDCap), via telephone, or in-person, based on preference and recruitment method. Eligibility criteria 
is as follows: 
Inclusion criteria: 
Eligible participants will 1) be 40-79 years of age, 2) have had a primary unilateral TKR within a 
year of the baseline assessment, 3) have an Android or iOS smartphone that is accessible and near 
them the majority of the day, 4) be willing to download the study applications on their smartphone, 
5) spend at least 7 hours/day sitting, and 7) be English-speaking 
Exclusion criteria: As all patients will be under physicians’ supervision post-TKR, participants will 
only be excluded if they 1) have any contraindications to activity, 2) have a mobility limiting 
comorbidity (e.g., spinal stenosis), 3) have a scheduled surgery (i.e., TKR on contralateral knee) 
within the next 6 months, or 4) do not have ≥4 days of valid accelerometer wear at baseline. 
2.  RECRUITMENT PLANS:  
Adults after knee replacement will be recruited using several recruitment approaches. Approved flyers 
will be hung, available in the waiting rooms, and distributed to potential candidates at Prisma Health 
Orthopedics. Prisma staff will regularly identify candidates who had knee replacement and provide the 
candidates name, address, phone number, and/or email address to study staff. Study staff will then 
make outreach via phone, email, or mail with approved recruitment materials to introduce the study to 
the candidate. Contact information will be destroyed following contacting the participant and assessing 
interest in participating. Additional recruitment strategies include: 1) Posting flyers and electronic blurbs 
for the UofSC campus (e.g., UofSC Today emails, TecHealth website); 2) posting flyers or postcards at 
local Columbia area businesses, health centers, and physical therapy clinics (e.g., Prisma Health 
Orthopedics Rehabilitation Centers); 3) electronic and social media blurbs (e.g., Twitter, Facebook); 
and 4) promotions in publications with low or no advertising cost.    
All recruitment materials will contain IRB approved information about the study, a link to our 
website to access the web screener, and study phone number in which participants can contact 
one of the study personnel if they have any questions regarding the study. Participants may be 
screened online (via REDCap), via telephone, or in-person, based on preference and 
recruitment method, to assess the study’s inclusion and exclusion criteria. Eligible candidates 
who completed the online screener will be contacted by telephone, to further discuss the study, 
and answer questions.  
3. EXISTING DATA/SAMPLES:  
Not applicable. 
 
4.  CONSENT/ASSENT: 
Eligible participants will be provided with a copy of the informed consent. Study staff will discuss full 
details of the study and answer any questions. Participants will be reminded that participation is 
voluntary. Disclosure will be made of the nature and potential risks of participating and all participants 
will be asked if they have any questions about their participation to ensure they understand the 
procedures. Participants will also be provided with a copy of the signed informed consent document at 
either the initial or the baseline appointment.  
5.  POTENTIAL RISKS: 
Risks associated with interrupting sedentary time with brief bouts of light-intensity physical activity such 
as standing or light ambulation are minimal. Since participants will have recently undergone total knee 
replacement, we will assess any type of events or adverse events that may occur, such as a fall. It is 
expected that some participants will still be experiencing pain and soreness from the surgery at the 

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start of the intervention; thus, the proposed study includes individual telephone calls with participants to 
allow the tailoring of goals related to reducing sedentary time that are consistent with participants 
recovery from knee replacement. Prior to the start of the intervention, participants will be encouraged to 
notify study staff of any event (study-related or not-study related) that occurs.  The research team will 
not make any diagnoses nor have access to participants’ medical records. Potential risks that may 
occur are: 
• 
Feelings of muscle soreness, fatigue, or pain may occur during physical function testing. 
Participants will be allowed to take breaks at any time during function tests. Standard 
procedures will be used to monitor participants and ensure safety. These procedures have been 
used in previous studies and no adverse events or outcomes have occurred implementing these 
assessments. 
• 
The use of the MyKneeGuide smartphone application or website poses a risk of loss of privacy.  
Participants will be provided with a confidential study name and email address to register on 
MyKneeGuide; however, participants will have the ability to post messages to other knee 
replacement patients on the app/website. Participants will be informed that they do not need to 
use a username that identifies them in the posts. 
• 
Participants may experience skin irritation from wearing the activPAL accelerometer for 7 days 
at each assessment. In the event the participant experiences skin irritation, we will ask the 
participant to remove the device. We will provide them with additional tape, with multiple options 
available to accommodate individual reactions and preferences to medical grade tape, to reaffix 
to the other leg. 
 
6.  POTENTIAL BENEFITS: 
Participants may or may not directly benefit from participating in this study. Participants may gain skills 
and knowledge regarding how to decrease sedentary behavior or general education related to recovery 
from total knee replacement. Participants who are adherent to the intervention and reduce sedentary 
time may have greater reductions in pain and improvements in physical function. If the intervention is 
effective, it may provide an innovative approach to reduce sedentary time following total knee 
replacement. 
7.  CONFIDENTIALITY 
To ensure participants information is confidential, all participants will be assigned a study ID, which will 
be used on all paper or electronic forms and the NEAT!2 smartphone application. All study files will be 
stored in locked cabinets or on password-protected computer data files or secure-websites that only 
authorized study personnel can access. All results will be presented in aggregate form and participants 
will not be identified personally in any scientific report or presentation. All study personnel will undergo 
or have completed the most up to date clinical training, human subjects, and confidentiality training 
prior to assisting with any aspect of the study. 
 
8. COMPENSATION: 
Participants will earn $15 for completing each of the 2- and 5-month assessments ($30 total). 
 
9.  WITHDRAWAL: 
Participants will be informed they can leave the research at any time without penalty. If a participant 
decides to withdraw, no more information will be collected. The participants will be made aware of this 
during the consent process. 
 
Any data collected during their participation may be used by the investigators for the purposes 
described above. Choosing not to be in the study will not result in any penalty or loss of benefit to which 
participants are entitled. Specifically, the choice not to be in this study will not negatively affect a 
participant’s right to any present or future medical treatment or his/her present or future employment. 

University of South Carolina Study Protocol v.7 
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10. SAFETY REPORTING: 
Definitions - An adverse event (AE) is any untoward medical occurrence in a subject during 
participation in the clinical study. An adverse finding can include a sign, symptom, abnormal 
assessment, or any combination of these. An Unexpected Adverse Event is any adverse event in which 
the specificity or severity of the event was not expected and not consistent with the risk information 
described in the protocol or consent form.  
A serious adverse event (SAE) is any adverse event that results in one or more of the following 
outcomes: 
- 
Death 
- 
A life-threatening event 
- 
Inpatient hospitalization or prolongation of existing hospitalization 
- 
A persistent or significant disability/incapacity 
- 
A congenital anomaly or birth defect 
- 
An important medical event based upon appropriate medical judgment 
An unanticipated problem (UP) is an incident, experience, or outcome that meets all of the following 
criteria:  
- 
Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
that are described in the protocol-related documents, such as the IRB-approved research 
protocol and informed consent document; and (b) the characteristics of the subject 
population being studied; 
- 
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 
- 
Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized. 
 
Classification of Expectedness – An event will be classified as unexpected if it occurs in one or more 
subjects or others participating and the event's nature, severity, or frequency is not consistent with 
either: 
a. The known or foreseeable risk of adverse events associated with the procedures involved in 
the research that are described in the protocol-related documents, such as the IRB-
approved research protocol and the current IRB-approved informed consent document; or 
b. the expected natural progression of any underlying disease, disorder, or condition of the 
subject(s) experiencing the adverse event and the subject's predisposing risk factor profile 
for the adverse event. 
Expected adverse events are events that may be expected. Expected adverse events for the current 
trial include skin irritation from the activity monitors, muscle soreness, pain, fatigue or injury during the 
physical function tests, and falls. 
Classification of AE Severity - AEs will be labeled according to severity, which is based on their 
impact on the patient. An AE will be termed “mild” if it does not have a major impact on the patient, 
“moderate” if it causes the patient some minor inconvenience, “severe” if it causes a substantial 
disruption to the patient’s well-being, “life threatening or disabling” if it is life threatening or disables the 
patient in any way, or “fatal” if death occurs. 
AE Attribution Scale - AEs will be categorized according to the likelihood that they are related to the 
study intervention. Specifically, they will be labeled definitely unrelated, unlikely related, possibly 
related, probably related, or definitely related to the study intervention.   

University of South Carolina Study Protocol v.7 
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Reporting and Follow-up - See DSMB Template – May 2020 for reporting template and Appendix A 
for all Reporting Forms. All DSMB reports (and the DSMB’s deliberations) will also be shared with 
NIAMS.  We will assess events at on the Health Events Forms at 2 and 5ms, as well as when we 
become aware of any event in between assessments. We will follow up with participants as needed to 
ensure full details of each event are obtained. 
AE Reporting: 
- 
All non-serious AE’s will be reported on the semi-annual report to DSMB and NIAMS.  
during the semi-annual DSMB. In the AE report, the DSMB will state that they have 
reviewed all AE reports. 
- 
All non-serious AE’s will be reported to IRB during annual reviews, unless they constitute an 
unanticipated problem involving risks to subjects or others.   
 
SAE Reporting: 
- 
Deaths will be reported to IRB within 24 hours of learning about the death. All other SAE’s 
besides death will be reported to IRB during annual reviews, unless they constitute an 
unanticipated problem involving risks to subjects or others.   
- 
All SAEs, including participant deaths, will be reported to NIAMS and the DSMB within 48 
hours of the PI becoming aware of the event. The DSMB feedback will also be shared with 
NIAMS. 
 
UP Reporting:  
- 
UPs will be reported to NIAMS and the DSMB within 48 hours of the PI becoming aware of 
the event. The DSMB feedback will also be shared with NIAMS. 
- 
UPs will be reported to IRB no later than 10 working days after the event or notification to 
the investigator that the event has occurred.  
 
11. Protocol Deviations: 
Definitions - A Protocol Deviation is any departure from the procedures and treatment plans as 
outlined in the protocol version submitted and approved by the USC Institutional Review Board (IRB). A 
protocol deviation is considered major if it: 
• 
Is intended to eliminate apparent immediate hazard to a research participant, 
• 
Impacts the health, safety or welfare of subjects or places subject at increased risk of harm 
(physical, psychological, economic, or social), 
• 
Concerns possible serious or continued non-compliance (see USC IRB Guidance re: 
NonCompliance at: http://www.orc.research.sc.edu/PDF/Non-compliance.pdf). 
 
A protocol deviation is considered minor if it does NOT: 
• 
Impact the health, safety or welfare of subjects or alters the risk/benefit ratio, 
• 
Compromise the scientific integrity of the data collected for the study, 
• 
Affect subjects’ willingness to continue participating in the study. 
 
Protocol Deviation Reporting: 
- 
Major protocol deviations will be reported to the IRB, NIAMS, and the DSMB within 48 hours 
of the PI becoming aware of the event. The DSMB feedback will also be shared with 
NIAMS. 
- 
Minor protocol deviations will be reported to IRB during continuing reviews and to the DSMB 
during semi-annual meetings. All reports from DSMB and their feedback will be given to 
NIAMS. 
 

University of South Carolina Study Protocol v.7 
13 
 
12.  Safety & Precautions from COVID-19 
The study team will follow all current UofSC and/or Prisma Health COVID-19 safety guidelines and 
procedures.  
Screening: If a study team member experiences any of the symptoms, has a temperature over 100°, or 
was in contact with anyone with COVID-19, they should remain at home and not come to campus or 
any study site locations.  As with staff, if any participant meets the criteria above, we will cancel the in-
person appointment. Some Prisma Health study site locations may also require all individuals to 
undergo screening (symptom & temperature check) prior to entering the facilities. 
 
Social Distancing: All unvaccinated study team members will be required to wear a face mask that 
covers their nose and mouth, except when in an office alone. Masks are required for everyone (staff 
and participants) at Prisma healthcare settings. Appointment times will be spaced out to avoid 
overlapping and allow timing for proper cleaning and disinfecting. 
 
Cleaning & Disinfecting. Study team members will wash their hands before and after each participant 
contact. Hand sanitizer will also be available for each in-person interaction. Frequently touched areas 
(e.g., desks, chairs, door handles, computer keyboard) and equipment (e.g., scale, stadiometer, cones, 
and stop watches) will be cleaned and disinfected using recommended EPA-registered disinfectants 
and/or alcohol-based wipes containing at least 70% alcohol in between each participant or use. New 
pens will be provided for each participant and cleaned and disinfected after each use. Activity monitors 
will be cleaned and disinfected and all activity bands and pouches will be washed using warm water in 
a washing machine before given to a participant. Activity monitors will be sealed in a storage bag after 
initialization and given or mailed to participants. Study staff will use a different set of monitors to explain 
how to wear them correctly.   
 
 
 
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