Physical Activity Pathway for Patients With Osteoarthritis in Primary Care
Phase: NA
Conditions: Osteoarthritis
Sponsor: University of North Carolina, Chapel Hill

 
Physical Activity Pathway for Patients with Osteoarthritis in Primary Care 
 
 
 
NCT number NCT04533711 
Document Date 08/05/2021 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Activity Pathway for Patients with Osteoarthritis in Primary Care 
 
Protocol Number: 20-2134 
 
NCT Number: NCT04533711 
 
Principal Investigator: Kelli D. Allen, PhD 
 
Sponsor: University of North Carolina at Chapel Hill 
 
Grant Title: Physical Activity Pathway for Patients with Osteoarthritis in Primary Care 
 
 
Grant Number: 4R33AG056568-03 
 
Funded by: 
National Institute on Aging of the National Institutes of Health 
 
Version Number: 4.0 
 
5 August 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Physical Activity Pathway for Patients with Osteoarthritis in Primary Care  
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Summary of Changes from Previous Version: 
 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
Section 
10.1.10  
Revised language 
Correction needed previous 
language stated NIAMS and should 
state NIA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
 
STATEMENT OF COMPLIANCE.………………………………………………………..………….....1 
INVESTIGATOR’S SIGNATURE…………………………………………………………………..……2 
1  
PROTOCOL SUMMARY…………………………………………………………………………... 3 
1.1 
Synopsis………………………………………………………………………………………3 
1.2 
Schema………………………………………………………………………………………. 5 
1.3 
Schedule of Activities………………………………………………………………………..6 
2 
 INTRODUCTION… ............................................................................................................ 7 
 2.1 
Study Rationale and Background…………………………………………………………. 7 
  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…………………………………………………………………. .. 9 
  2.2.1  Known Potential Risks……………………………………………………………………....9 
  2.2.2 Known Potential Benefits…………………………………………………………………. 10 
  2.2.3 Assessment of Potential Risks and Benefits…………………………………………….10 
3 
STUDY OBJECTIVES AND ENDPOINTS ......................................................................... 10 
4 
STUDY DESIGN………………………………………………………………………………… .. 12 
 4.1  
Overall Design………………………………………………………………………………12 
 4.2  
Scientific Rationale for Study Design ....................................................................... 12 
 4.3   
Justification for Intervention ..................................................................................... 12 
 4.4  
End-of-Study Definition ........................................................................................... 13 
5 
STUDY POPULATION…………………………………………………………………………….13 
 5.1  
Inclusion Criteria ..................................................................................................... 13 
 5.2  
Exclusion Criteria .................................................................................................... 13 
 5.3  
Lifestyle Considerations .......................................................................................... 14 
 5.4  
Screen Failures……………………………………………………………………………..14 
 5.5  
Strategies for Recruitment and Retention………………………………………………. 14 
6 
STUDY INTERVENTIONS 
 6.1  
Study Intervention Administration ............................................................................ 15 
 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……………………………………… ... 18 
 7.1   
Discontinuation of Study Intervention…………………………………………………… 18 
 7.2   
Participant Discontinuation/Withdrawal from the Study……………………………… . 18 
 7.3   
Lost to Follow-up………………………………………………………………………… .. 19 
8 
STUDY ASSESSMENTS AND PROCEDURES……………………………………………… . 19 
 8.1  
Endpoint and Other Non-Safety Assessments………………………………………… 19 
 8.2  
Safety Assessments……………………………………………………………………… . 21 
 8.3  
Adverse Events and Serious Adverse Events………………………………………… . 21 
8.3.1  Definition of Adverse Events……………………………………………………………. .21 
8.3.2  Definition of Serious Adverse Events………………………………………………….... 21 
8.3.3  Classification of an Adverse Event……………………………………………………. ... 21 
8.3.4  Time Period and Frequence for Event Assessment and Follow-up…………………..22 

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8.3.5  Adverse Event Reporting………………………………………………………………. ... 22 
8.3.6  Serious Adverse Event Reporting……………………………………………………… . 23 
8.3.7  Reporting Events to Participants……………………………………………………….. . 23 
8.3.8  Events of Special Interest……………………………………………………………….. . 23 
8.3.9  Reporting of Pregnancy………………………………………………………………….. . 23 
 8.4  
 Unanticipated Problems………………………………………………………………… ..23 
8.4.1  Definition of Unanticipated Problems…………………………………………………….23 
8.4.2  Unanticipated Problems Reporting……………………………………………………… 24 
8.4.3  Reporting Unanticipated Problems to Participants……………………………………. 24 
9 
STATISTICAL CONSIDERATIONS ...……………………………………………………….. .. .24 
9.1   
Statistical Hypotheses…………………………………………………………………… . 24 
9.2   
Sample Size Determination……………………………………………………………… 25 
9.3  
Populations for Analyses…………………………………………………………………. 25 
9.4  
Statistical Analyses……………………………………………………………………… .. 25 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............... 26 
 10.1 Regulatory, Ethical, and Study Oversight Considerations…………………………………. 26 
10.1.1  Informed Consent Process……………………………………………………………….. 26 
10.1.2  Study Discontinuation and Closure……………………………………………………… 27 
10.1.3  Confidentiality and Privacy………………………………………………………………. . 27 
10.1.4  Future Use of Stored Specimens and Data……………………………………………. 28 
10.1.5  Key Roles and Study Governance………………………………………………………. 29 
10.1.6  Safety Oversight…………………………………………………………………………… 29 
10.1.7  Clinical Monitoring………………………………………………………………………… 29 
10.1.8  Quality Assurance and Quality Control…………………………………………………..29 
10.1.9  Data Handling and Record Keeping…………………………………………………….. 30 
10.1.10 Protocol Deviations………………………………………………………………………. 30 
10.1.11 Publication and Data Sharing Policy…………………………………………………… 30 
10.1.12 Conflict of Interest Policy………………………………………………………………… 31 
 10.2 
Additional Considerations………………………………………………………………… 31 
 10.3 
Abbreviations and Special Terms……………………………………………………… .. 31 
 10.4 
Protocol Amendment History……………………………………………………………. . 33 
11  
References………………………………………………………………………………………34 
 
 
 
 
 
 
 
 
 
 

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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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1 
PROTOCOL SUMMARY 
 
 
1.1 
SYNOPSIS 
 
 
Title: 
Physical Activity Pathway for Patients with Osteoarthritis in Primary 
Care 
Grant Number: 
4R33AG056568-03 
Study Description: 
The overall objective of this study is to conduct a randomized pilot 
trial of the Osteoarthritis Physical activity Care Pathway (OA-PCP) 
among n=240 patients with knee and/or hip OA recruited from UNC 
Health Care and affiliated clinics within the UNC Physicians 
Network, as well as Piedmont Health Services. Specific hypotheses 
are as follows: 
 
H1:   Participants in OA-PCP intervention will have greater 
improvement in objectively assessed physical activity (PA), 
measured at 6 and 12 months, compared to participants in an 
attention control group. 
 
H2:   Participants in OA-PCP intervention will have greater 
improvement in self-reported physical function and pain, measured 
at 6 and 12 months, compared to participants in an attention control 
group. 
 
 
Objectives*: 
 
Specific Aim 1:  Obtain data on the efficacy of the OA-PCP 
program. 
Specific Aim 2: Refine the OA-PCP based on feedback from 
patients and clinic personnel in preparation for a larger, 
implementation-focused trial. 

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Endpoints*: 
Primary Endpoint: 
Objectively assessed PA, measured via accelerometer.  The 
primary metric of interest is minutes of moderate to vigorous 
physical activity (MVPA). Other metrics will include light intensity 
PA, sedentary minutes and step counts.  These will be assessed at 
baseline and 6-month and 12-month follow-up time points.   
 
Secondary Endpoints:  Self-reported pain and function (Western 
Ontario and McMaster Universities Osteoarthritis Index; WOMAC).  
These will be assessed at baseline and 6-month and 12-month 
follow-up time points.   
 
Exploratory Endpoints:  Fatigue numeric rating scale, self-reported 
PA, self-reported sleep, Patient Global Impression of Change and 
pain medication usage. 
 
Feasibility and acceptability metrics include recruitment, retention, 
intervention delivery, and outcome assessment. Perceptions of 
acceptability will be obtained from patients using open-ended 
questions. 
 
Study Population: 
N = 240 participants age ≥65 recruited from primary care clinics 
within UNC Health Care and affiliated clinics within the UNC 
Physicians Network, as well as Piedmont Health Services. We will 
enroll both males and females from any racial / ethnic background.   
 
Phase* or Stage: 
Based on the Obesity-Related Behavioral Intervention Trials 
(ORBIT) framework, this study is a Phase IIb trial. 
 
Description of 
Sites/Facilities Enrolling 
Participants: 
Patients are eligible of they have received care at any site within 
UNC Health Care or affiliated clinics within the UNC Physicians 
Network, as well as Piedmont Health Services. 
 
 
Description of Study 
Intervention/Experimental 
Manipulation: 
The OA-PCP will include four phases. Phase 1:  Physical Activity 
Screening: This component of the OA-PCP will be completed as 
part of the enrollment process. Phase 2:  Brief PA Counseling:  This 
will be delivered via phone by a PA Coach, who will be trained in 
relevant aspects of PA and motivational interviewing.  Phase 3:  
Linkage to PA Programs and Resources Phase; 4:  PA Coaching 
Follow-Up. The PA coach will call participants approximately 3, 6, 9 
and 12 months following the initial call, with periodic check-in emails 
in between calls. The coaching calls will focus on PA goal-setting, 
and participants will be provided with an activity tracker to facilitate 
PA self-monitoring.  
Study Duration*: 
2-3 years 
Participant Duration: 
12 months 
 
 
 
 

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1.2 
SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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INTRODUCTION 
 
2.1 
STUDY RATIONALE AND BACKGROUND 
 
 
2.1.1. CLINICAL SIGNIFICANCE  
Osteoarthritis (OA) is a Major Cause of Pain and Disability among Older Adults 
OA is one of the most prevalent chronic conditions in the U.S.  Lifetime risks of symptomatic knee and hip OA 
are 45% and 25%, respectively 1,2, and the prevalence of OA is expected to rise dramatically over the next 
several decades 3.  The incidence of OA begins to rise around age 50 years, and OA affects about 1/3 of 
adults age ≥65 years 4,5.  OA is associated with significant pain, functional limitations, and poorer health-related 
quality of life 6.  Among older adults, the risk of disability attributable to knee OA is as great as that due to 
cardiovascular disease and greater than any other medical condition 7.  In addition, studies show that arthritis 
is a significant barrier to engagement in physical activity (PA) among individuals who are overweight and those 
who have diabetes and cardiovascular disease 8-10; therefore addressing OA symptoms is also critical for 
management of common comorbid health conditions. 
Physical Activity is Essential for OA Management, But Most Patients are Inactive 
Guidelines consistently include PA as a core component of managing knee and hip OA 11-13, based on its 
strong evidence for effectiveness 14.  A meta-analysis of trials of PA for knee OA found that effect sizes for 
aerobic exercise were 0.52 and 0.46 for pain and disability, respectively; for strengthening exercises, effect 
sizes were 0.39 and 0.3215. These are moderate to large effect sizes and are comparable to those observed 
for pharmacological treatment of OA 16.  Among patients with hip OA, meta-analysis also showed that land-
based exercise substantially reduced pain and improved physical function – providing 28% and 24% 
improvement from baseline, respectively 17.  Despite strong evidence for PA in managing OA symptoms, it is 
substantially under-utilized 18,19.  For example, in a study of adults who had or were at risk for knee OA, only 
2% of African Americans and 13% of Caucasians were currently meeting PA recommendations 19. There is an 
urgent need to improve PA levels among older adults with OA, particularly to reduce risk for downstream 
functional limitations and disability.   
Primary Care is a Key But Under-Utilized Setting for Promoting PA 
The vast majority of patients with OA are seen in primary care, which therefore represents a key opportunity to 
integrate PA into a comprehensive OA management approach 20.  Yet evidence shows that we are failing to 
bring PA into the conversation about OA management 21.  For example, in one study less than half of inactive 
patients with arthritis (primarily OA) reported that a doctor had ever suggested PA as a strategy to help 
manage joint symptoms 22, despite the fact that exercise is included as a first-line therapy in OA treatment 
guidelines 23.  This is in contrast to the overwhelming majority of patients who take pain medications to help 
manage OA symptoms 24. Other data show that only 1/3 of patients overall receive advice to increase PA from 
a primary care provider 25. There are a number of reasons that health care providers infrequently recommend 
or counsel patients about PA, including include lack of routine PA screening, lack of time within clinic visits, 
and lack of provider confidence in skills to deliver PA counseling 20.  These challenges are addressed in our 
proposed intervention approach.   
Evidence supports the effectiveness of PA interventions within primary care settings 20,26-28.  However, we have 
failed to move this evidence toward implementation, as PA is still not incorporated into health care delivery 
models. The following are critical gaps that must be addressed in order to successfully integrate PA 
interventions into primary care, each of which will be addressed by this study: 
• 
Approach for Regular PA Screening:  Prior studies suggest that incorporation of routine PA screening into 
health care settings can facilitate clinician-patient conversations about PA 29,30.  However, studies have not 
examined models that systematically follow up on PA screening with an intervention for those who are inactive.  
• 
Approach to Sustainable Intervention Delivery:  A key reason that PA interventions have not been 
integrated into clinical settings is the lack of feasible delivery models, both in terms of organization and 
financial support. This project will develop and test an intervention that can be delivered within the context of 
the Center for Medicare and Medicaid Services (CMS) Chronic Care Management (CCM) services, as 
described below.  This provides a practical model for both reimbursement and intervention delivery personnel.  

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• 
Implementation Science-Based Approach to Development:  Models for PA interventions in primary care 
must have input from key stakeholders throughout all phases of the development and testing processes  31. 
These stakeholders include patients and their supportive partners, primary care personnel, and representatives 
of clinical and community-based PA programs 
 
 
 
2.1.2. PREMISE 
Developing an OA Physical activity Care Pathway (OA-PCP) for Primary Care Settings 
We initially developed the OA-PCP model based on: 1) key recommendations for PA interventions in primary 
care, 2) the “Let’s Get Moving” intervention, 3) the Socioecological Model of Health Behavior, and 4) CMS 
guidelines for delivering CCM services:   
Key recommendations for PA interventions in primary care, based on prior studies, include: use of trained 
coaches to deliver the PA intervention, engagement of patients as active participants who select goals and 
identify strategies to overcome barriers, inclusion of follow-up contacts and tailored feedback, and integration 
with community-based and other PA resources 20,27.  
The “Let’s Get Moving” intervention is a systematic approach to integrating PA into primary care that was 
implemented in United Kingdom general practices based on research evidence 32-34. This model involves four 
phases: 1.) Screening for physical inactivity in a primary care setting, 2.) Brief PA counseling intervention, 3.) 
Connection with community and other PA resources, 4.) Follow-up to assess progress and promote 
maintenance. The OA-PCP mirrors these four phases.   
The Social Ecological Model of Health Behavior has been 
applied to many interventions and emphasizes the unique 
and complementary strengths of intervention components 
at different levels 35,36.  As shown in Figure 1, OA-PCP 
components address the individual and interpersonal 
levels though PA counseling, the organizational level via 
systematic PA screening and intervention initiation in 
primary care, and the community level by linking patients 
with programs and resources.  The ultimate goal of this 
research is to provide a strong evidence base that will 
lead to public policy level initiatives such as systematic, 
widespread roll-out and quality measures related to PA 
screening and intervention in health care systems.  
CCM services were initiated by the CMS in 2015, and 
provision of these services has been growing under this 
model and reimbursement structure; CMS is actively 
promoting delivery of these services. Briefly, these 
services provide “at least 20 minutes of clinical staff time, 
directed by a physician or other qualified health care 
professional, per calendar month,” for patients with two or 
more chronic health conditions.  OA is one of the 
qualifying chronic conditions, and many conditions that 
commonly co-occur with OA also qualify (e.g. diabetes, 
depression, hypertension, cardiovascular disease). Therefore, a large proportion of patients with Medicare 
coverage who have OA are eligible for these services. PA counseling could be delivered as a component of 
CCM services, since these include addressing patients’ functional needs, referrals to other clinicians and 
community-based services, patient education, motivational counseling and self-management support.  
Embedding PA counseling within the context of CCM services is appealing because it integrates PA within the 
broader disease management process.  Importantly for the structure of the OA-PCP, CCM services do not 
need to be delivered by the billing practitioner; they may be delivered by other clinic staff under the direction of 
the billing practitioner. Some primary care clinics at our institution (University of North Carolina at Chapel Hill 

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(UNC)) are currently delivering these services using a model that involves “care assistants” (typically 
individuals with Bachelor Degree level of education in an appropriate field who are given training in CCM) who 
are supervised by billing practitioners. Also importantly for the OA-PCP, CCM services can be delivered via 
telephone, which is a typical delivery model at UNC. This project focuses on patients who are eligible for CMS 
CCM services, since this is a currently active reimbursement model and since many patients with OA are age 
65 or older.   
 
 
2.1.3. PRIOR STUDIES AND RATIONALE FOR DEVELOPMENT 
Overall Experience of the Research Team 
This project builds on the collective experience of our study team in OA management, PA interventions, and 
primary care-based studies.  Dr. Allen’s has led 8 clinical trials of behavioral and health services interventions 
among individuals with OA 37-43.  Of high relevance to this project were two randomized clinical trials of patient 
and provider based interventions for managing OA in primary care 37,44. These studies directly interfaced with 
primary care clinics, showing the feasibility of this approach and our experience with these types of 
interventions. Dr. Callahan is an international leader in evidence-based PA programs for OA, particularly 
community-based and self-directed interventions.  She led the evaluation of the Arthritis Foundation Walk With 
Ease program and 5 other PA intervention trials 45-52.  She participated in development of the National Public 
Health Agenda for OA and directs the Osteoarthritis Action Alliance (OAAA), a coalition of more than 95 
organizations committed to increasing PA among individuals with OA 53. Dr. Golightly is a physical therapist 
and epidemiologist with expertise in the clinical aspects of OA and PA intervention approaches for OA 54. She 
serves as the Grants Program Manager for the OAAA, partnering with communities and healthcare systems 
nationwide to implement evidence-based PA programs for people with OA.  Dr. Nelson is a rheumatologist with 
expertise in OA diagnosis, clinical care and epidemiology.  She is also the medical advisor for the OAAA and 
leads an OAAA workgroup focused on health systems and OA management. Dr. Cleveland is an 
epidemiologist and statistician with extensive expertise in conducting analyses related to OA and PA, as well 
as other outcomes. Dr. Powell is an implementation scientist who has expertise in understanding strategies to 
implement effective health services interventions 55-57.  Dr. Vu is a qualitative methodologist who has 
contributed to many studies that conduct formative assessments of multi-level and health system based 
interventions 58-60.  Dr. Hales is an expert in use of accelerometers to measure PA 61,62 and is currently 
collaborating with Dr. Callahan on a study of partner-focused PA among individuals with arthritis.   
This protocol covers study activities for Aim 3 of a 3-Aim project. In Aim 1 we developed OA-PCP based on 
input obtained during focus groups and interviews with patients with OA, spouses / support partners, clinic 
personnel and community organization representatives 63.    In Aim 2 we conducted a pilot trial to assess the 
feasibility and acceptability of OA-PCP among 60 participants with hip and / or knee OA.  Results supported 
the feasibility and acceptability of the program 64.   
 
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 necessary for 
the study. To minimize breaches of confidentiality, all data will be stored on a secure UNC server and paper 
information will be stored in locked filing cabinets in the office of a study team member, and only approved 
study personnel will have access to those data. 
 

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Risks of Exercise: The physical activity coach will give participants information on exercise programs 
appropriate for people with OA. This information follows guidelines recommended by physicians and 
researchers. However, exercise programs may be associated with risk of injury, muscle soreness, and joint 
pain. The risk of sudden death during physical activity is about 1 death per 656,000 hours of physical activity. 
In general, the risk of these events with moderate physical activity is very low. 
 
2.2.2 KNOWN POTENTIAL BENEFITS 
 
Participants may experience improvements in pain, physical function or other symptoms related to OA, from 
participating in the OA-PCP program. It is possible that this study may not benefit participants directly, but 
participation in this study may lead to information that can benefit other patients with knee and hip OA, as well 
as their health care providers. 
 
 
2.2.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
This is a minimal risk study with physical risks that are comparable to those that would be encountered with 
exercise programs in clinical or community settings.  Furthermore, we do not anticipate any significant 
psychological, social, financial, or legal risks to be associated with participation in this study.  Given the high 
and increasing rate of OA, the persistent deficits of physical inactivity, and the lack of a standard, evidence-
based approach to address these deficits in primary care settings, we believe the value of the information to be 
gained outweighs the risks of participation in the study. 
 
3  
STUDY OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary 
Obtain data on the 
efficacy of the OA-PCP 
program on objectively 
assessed PA, measured 
via accelerometer. 
H1  Participants in OA-PCP 
intervention will have 
greater improvement in 
objectively assessed PA, 
measured at 6 and 12 
months, compared to 
participants in an attention 
control group.  
 
 
MVPA (primary metric), light 
intensity activity, sedentary 
minutes, step counts and 
other PA metrics, assessed 
at baseline, 6 months and 12 
months.   
 
 
MVPA was chosen as the primary metric 
because it corresponds to Department of 
Health and Human Services (DHHS) PA 
recommendations.  Other complementary PA 
metrics are also important for describing the 
overall activity patterns of participants.  The 
12-month time point corresponds to the end 
of OA-PCP calls, and the 6-month time point 
will allow assessment of the time courses of 
changes in outcomes.    
Secondary 
Obtain data on the 
efficacy of the OA-PCP 
program with respect to 
improvement in self-
reported physical 
function and pain.  
H2  Participants in OA-PCP 
intervention will have 
Western Ontario and 
McMaster Universities 
Osteoarthritis Index 
(WOMAC) pain and function 
subscales, assessed at 
baseline, 6 months and 12 
months.   
These secondary metrics will be assessed 
because they are key outcomes in OA and 
can be improved with regular PA. The 12-
month time point corresponds to the end of 
OA-PCP calls, and the 6-month time point will 
allow assessment of the time courses of 
changes in outcomes.    

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
greater improvement in 
self-reported physical 
function and pain, 
measured at 6 and 12 
months, compared to 
participants in an attention 
control group. 
Tertiary / Exploratory  
Obtain data on the 
efficacy of the OA-PCP 
program with respect to 
the change in 
exploratory outcomes. 
 
 
 
 
 
 
 
 
 
 
 
Assess the feasibility 
and acceptability of the 
OA-PCP program. 
 
 
Exploratory outcomes 
include self-reported fatigue 
(Stanford Numeric Rating 
Scale), self-reported physical 
activity (Modified version of 
the Community Health 
Activities Model Program for 
Seniors; CHAMPS), self-
reported sleep (PROMIS 
Sleep Disturbance) and pain 
medication usage assessed 
at baseline, 6 months and 12 
months. Perceived Impact of 
COVID-19 and the Valuing 
Questionnaire assessed at 
baseline. Patient Global 
Impression of Change 
assessed at 6 months and 
12 months.  
 
 
Feasibility and acceptability 
metrics include recruitment, 
retention, intervention 
delivery, and outcome 
assessment. Perceptions of 
acceptability will be obtained 
from patients and providers 
from each clinic using open-
ended questions. 
 
 
Fatigue is an important patient-centered 
outcome for patients with OA, closely linked 
with pain.  Self-reported PA is a useful 
complement to accelerometer-based 
measurement, providing information on the 
contexts and types of activities in which 
participants are engaging. Patient Global 
Impression of Change scale evaluates 
participants’ perspectives on overall changes 
in their joint pain during the study period. 
Self-reported sleep assesses sleep-related 
impairment. Pain medication use evaluates 
common treatments for patients with OA.    
The 12-month time point corresponds to the 
end of OA-PCP calls, and the 6-month time 
point will allow assessment of the time 
courses of changes in outcomes.    
 
 
 
This information is important for planning for 
a future, larger implementation-focused trial 
and for refining the OA-PCP intervention as 
needed. 
 
 
 
 
 
 
 
 
 
 
4  
STUDY DESIGN 

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4.1  
OVERALL DESIGN   
The aim of this study is to conduct a randomized pilot trial of the refined OA-PCP among n=240 
patients with knee and / or hip OA. Sub-aims and hypotheses are:  
1.  Obtain data on the efficacy of the OA-PCP. 
H1  Participants in OA-PCP intervention will have greater improvement in objectively assessed PA, 
measured at 6 and 12 months, compared to participants in an attention control group.  
H2  Participants in OA-PCP intervention will have greater improvement in self-reported physical function and 
pain, measured at 6 and 12 months, compared to participants in an attention control group. 
2.  Refine the OA-PCP based on feedback from patients, clinic personnel, and community representatives, in 
preparation for a larger, implementation-focused trial.  
 
This study will be a randomized trial with participants assigned 
equally to either the OA-PCP or an attention control group (Figure 
2).  To enhance generalizability, we will involve patients broadly 
from UNC Health Care and affiliated clinics within the UNC 
Physicians Network as well as Piedmont Health Services. 
Randomization will be based on a computer generated sequence 
maintained by the project statistician in a database. Participants 
will be notified of their randomization assignment by the study 
coordinator, following completion of baseline assessments. Study 
patients will complete assessments at baseline, 6 months and 12 
months.  The 12-month time point corresponds to the end of OA-
PCP follow-up calls (described below), and the 6-month time 
point allows assessment of the time course of changes.   
 
4.2   
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
The use of an attention control group was selected to account for 
potential effects of intervention-related contacts (e.g., “attention”) 
that are not specific to the OA-PCP intervention components 
(e.g., PA counseling, goal-setting, linkage to PA resources).  
 
4.3  
JUSTIFICATION FOR INTERVENTION 
 
The Scientific Premise and Prior Studies sections above describe 
the prior literature, recommendations and preliminary studies that 
have informed development and refinement of the OA-PCP 
components.  The number, frequency and types of contacts were 
selected based on feasibility to deliver within CMS CCM services.  
Content of each PA counseling contact is based on scientific 
evidence related to behavior change and successful strategies for 
increasing PA 20,27,35,70.    
 
 
 
 
 
4.4  
END-OF-STUDY DEFINITION 
 

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A participant is considered to have completed the study if he or she has completed 12-month follow-up 
assessment.  
 
5   
STUDY POPULATION  
 
5.1  
INCLUSION CRITERIA 
 
Participants need to be age 65 or older, and have, in addition to OA, one other chronic health condition that 
qualified under CCM guidelines, including: diabetes, depression, hypertension, hyperlipidemia, heart failure, 
atrial fibrillation, ischemic heart disease, stroke/TIA, peripheral vascular disease, COPD, bronchiectasis, 
asthma, rheumatoid arthritis, osteoarthritis, HIV/AIDS, chronic kidney disease, hepatitis (chronic & viral B & C) 
and osteoporosis.  Other inclusion criteria are:  1) Self-reported current symptoms in a joint with OA, using the 
following validated item: “Do you have pain, aching or stiffness in your knees/hips on most days?” 71. Patients 
also had to self-report a pain score of ≥3 on a 0-10 numeric scale (0=no pain, 10=extreme pain), which is an 
approach recommended by the Osteoarthritis Research Society International Clinical Trial Guidelines 72.  2) 
Self-reported physical activity <150 minutes per week, which aligns with public health recommendations. We 
will use the Physical Activity Vital Sign (PAVS) 29,73-75, which includes the following two questions:  1. “On 
average, how many days a week do you engage in moderate to strenuous exercise (like a brisk walk)?” 2. “On 
average, how many minutes do you exercise at this level?”  The PAVS has been implemented in a large health 
care system, showing good face and discriminant validity 29,30.  We also selected this physical activity 
screening approach because would be feasible to administer in primary care settings as part of implementing 
OA-PCP.  3) Willing to make a change in their PA over the next 3 months. 
 
5.2  
EXCLUSION CRITERIA 
 
Exclusion Criteria and Sources of Information  
Criterion  
EMR 
Phone Screening  
Pain in chest when performing 
physical activity 
 
X 
Pain in chest when not performing 
physical activity 
 
X 
Loss of balance because of dizziness 
or loss of consciousness 
 
X 
Recommendation from doctor to only 
perform physical activity under 
medical supervision 
 
X 
No documented diagnosis of knee or 
hip OA 
X 
 
Dementia 
X 
X 
Psychosis 
X 
 
X 
Active Substance abuse disorder 
X 
X 
Total knee or hip replacement 
surgery, meniscus tear, ligament tear, 
or other significant lower extremity 
injury or surgery in the last 6 months 
X 
X 
Severe hearing or visual impairment 
X 
X 
Serious/terminal illness as indicated 
by referral to hospice or palliative care 
X 
X 
Unstable angina 
X 
X 
Hospitalization for cardiovascular 
event in last 6 months 
X 
X 
History of ventricular tachycardia 
X 
X 

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Unstable chronic obstructive 
pulmonary disease (2 hospitalizations 
within the previous 6 months and/or 
on oxygen) 
X 
X 
Stroke with moderate to severe 
aphasia 
X 
X 
Recent history (last 6 months) of 
three or more falls 
 
X 
Planning total joint replacement in 
next 6 months 
 
X 
Other health problem that would 
prohibit safe physical activity 
participation 
 
X 
Current participation in other study 
related to knee or hip osteoarthritis or 
physical activity 
 
X 
Unable to speak English 
X 
X 
 
 
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.   
 
5.5.  
STRATEGIES FOR RECRUITMENT AND RETENTION  
Potential participants will first be identified using the electronic medical record (EMR). Specifically, we will 
identify patients age 65 and older with diagnosis codes for knee or hip OA (M17.0, M17.10, M17.11, M17.12, 
M17.2, M17.30, M17.31, M17.32, M17.4, M17.5, M17.9, M16.0, M16.10, M16.11, M16.12, M16.2, M16.30, 
M16.31, M16.32, M16.4, M16.50, M16.51, M16.52, M16.6, M16.7, M16.9, M19.90, M19.91, M19.92, M19.93, 
M15.0 (primary, generalized OA)), a diagnosis code for at least one qualifying comorbid health condition under 
CCM guidelines listed above, and no diagnosis codes for exclusionary health conditions. We will include 
patients who have been seen within UNC by a primary care provider during the past 2 years, including Internal 
Medicine, Family Medicine and Geriatrics clinics.  Primary care providers may, if they choose, review lists of 
patients eligible based on the EMR and approve a final list of patients to contact, but this is not a requirement.  
These patients will be mailed an introductory letter and then called by a study team to further assess eligibility.  
Patients who are eligible and interested in participating will complete a verbal consent process which will 
include verbal HIPAA authorization.  Then participants will complete baseline assessments via telephone and 
be mailed an accelerometer for physical activity assessment.  Participants will be paid $25 for completing each 
phone-based assessment and $15 for returning the accelerometer at each time point.  Following return of the 
accelerometer at baseline, an unblinded study team member will call the participant to inform them of their 
randomization assignment.  Participants assigned to the OA-PCP group will then be mailed an Activity Tracker 
and instructions and asked to begin wearing it as soon as they receive it.  About a week after the Activity 
Tracker is mailed, an unblinded study team member will call the participant to answer any questions about 
device wear and setup.  We will aim for the participant to wear the Activity Tracker for at least 1 week prior to 
the first OA-PCP call, so that PA goals can be based on current activity patterns. Participants will also be 
notified that the PA Coach will be able to view their Activity Tracker data using Fitabase®.  
 

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Participants in both the intervention and control group will have regular contact with an interventionist 
throughout the study period. Based on our prior studies, we believe this will enhance retention. In addition, we 
believe that the lack of requirement for any in-person study visits will enhance both recruitment and retention.  
To facilitate completion of recruitment calls, as well as baseline and follow-up assessment calls, we will call 
participants on different times of day and different days, across multiple weeks.  We have used this strategy 
successfully in prior studies to reach participants at times convenient to them.  
6.0  
STUDY INTERVENTIONS  
6.1  
STUDY INTERVENTION ADMINISTRATION 
 
OA-PCP Intervention   
As summarized in Figure 3, the OA-PCP will include four phases, with a total intervention period of 12 months. 
Phase 1:  Physical Activity Screening 
This component of the OA-PCP will be completed as described above within the recruitment and enrollment 
process.  Although it is framed within the recruitment process here, it has been designed to mirror a PA 
screening process that could occurred routinely in primary care.    
Phase 2:  Brief Initial PA Counseling 
This will be delivered via phone by the PA Coach, who will be trained in relevant aspects of PA and 
motivational interviewing.  The content for the initial call is designed to be brief enough that it can be 
embedded within a routine CCM call; future calls are even shorter.  We have developed detailed scripts for all 
OA-PCP calls.  The following are key components of the first PA counseling call:  
1. Description of the Benefits and Appropriateness of PA for OA:  This content includes a brief summary of 
benefits of PA and basic information for safe, appropriate PA in the context of OA. With regard to aerobic 
activity, the PA Coach will encourage participants that good long-term goals are to do 150 minutes of moderate 
intensity activity per week and or 7,500-10,000 steps per day, per general public health recommendations and 
recent research evidence 76,77. However, the Coach will also stress the value and health benefits of interim 
goals when increasing amount of weekly aerobic activity.  In addition, goal-setting for aerobic activity will be 
framed around benchmarks of particular relevance for people with OA, as described below.  With respect to 
strengthening exercises, participants will be encouraged to perform these at least twice per week on non-
consecutive days 78.  Lower extremity strengthening exercises will be emphasized.  Participants will be 
encouraged to perform stretching exercises daily.  Instructions and example strengthening and stretching 
exercises are included in the Arthritis Foundation brochure described below.   

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2. PA Goal-Setting:  The Coach will work with participants to establish and document PA goals, with an initial 
focus on the next 2 weeks (before check-in call; Figure 3). Participants will be asked to focus their PA goals on 
either step counts or activity minutes; monitoring for each of these will be facilitated by use of the Activity 
Trackers.   Recent research has identified important metrics for reducing risks of functional limitation and 
disability among individuals with OA.  In particular, thresholds of 60 weekly minutes of MVPA and 6,000 steps 
per day as important targets 79,80.  Participants will be asked to select one of these benchmarks as a minimum 
goal to work toward during the one-year time period of the intervention. If participants meet one of these goals, 
they will be encouraged to work toward broader public health goals of 150 minutes of MVPA per week or 
7,500-10,000 steps per day 76,77.  Participants may also switch from step-focused goal to an activity minute-
focused goal as the OA-PCP calls progress.  As noted above, initial goals will be based on participants’ current 
PA data (e.g., at least 1 week of Activity Tracker wear).  The PA Coach will inform participants that s/he will be 
able to monitor their PA (using Fitabase ®), with their permission, based on data from the Activity Tracker, and 
describe that this will enhance the “partnership” of this program, allowing the Coach to observe specific PA 
patterns and potential opportunities to enhance activity during the day.  As part of the goal-setting process, the 
Coach will talk with participants about potential barriers and use a problem-solving approach to address each 
one.  
3. Discussion of Preferences for PA and Identifying Appropriate PA Resources: The Coach will ask 
participants brief questions to understand types of PA they enjoy most and are likely to engage in. Based on 
this information, at the 2-week call, the Coach will recommend specific PA programs resources that can help 
them progress toward their PA The coach will also review participants’ progress toward PA goals and set new 
goals.  If participants have encountered any barriers to PA since the first call, they will be addressed and other 
PA resources identified if needed.   
4. Follow-up emails: The study team will ask participants to opt-in (or opt-out) to receive follow-up emails at 1-
month and 2-month time points after the initial call.  The content of the emails will be based on individual PA 
goals set during previous check in calls.   
Phase 3:  Linkage to PA Programs and Resources  
There are a large number of OA-appropriate, evidence-based PA resources, and a collection of these 
resources has been developed (and is updated on an ongoing basis) by the OAAA at UNC; a key source for 
informing this collection is the CDC’s Compendium of Arthritis Appropriate Physical Activity and Self-
Management Education Interventions.  Table 1 shows representative examples of these resources, which 
include tools to facilitate individual PA, as well as group-based classes. With regard to the latter, we will 
perform an environmental scan for programs available within the communities surrounding study clinics; this 
will be facilitated by the OAAA, the Arthritis Foundation’s Online Resource Finder and the Evidence-Based 
Leadership Council. Based on our prior experience 38, there are many free, appropriate PA programs available 
in communities, including walking groups and classes in senior centers.   
 
Local resource information will be used to tailor patient handouts.  Participants will be able to contact the PA 
Coach throughout the intervention period if they have questions about PA resources, or if they would like 
information on different resources.  We will document the frequency and nature of the contacts to inform and 
refine the intervention. 
 
Table 1.  Example OA-Appropriate PA Resources and Programs 
Self-Directed 
Walk With Ease 
(Self-Directed) 
Resources to help people with arthritis learn to walk safely and regularly.  
Tools include a guidebook, walking diary, example exercises, interactive 
online resources (starting point test, motivational tools, activity log) and a 
mobile app. COST: Free 
Exercises for 
Chronic 
Conditions  
Exercise CDs developed by Stanford University, appropriate for people 
with arthritis and other chronic health conditions. COST: $10 

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Phase 4:   
PA 
Counseling Follow-Up   
The PA Coach will call participants at three month intervals following the initial call (e.g., 3-, 6-, 9- and 12 
months), again using our developed phone scripts and tailored based on earlier calls. These calls will focus on 
reviewing progress toward PA goals, PA patterns observed in Fitabase ®, identifying additional PA resources if 
needed, and working with participants to set new PA goals as they progress.  During the 3-month call, the 
coach will briefly review instructions for strengthening and stretching exercises, to complement step or activity 
minute goals.  During the 6-month call, the PA Coach will provide tips for identifying setbacks in PA and work 
with participants to identify strategies for dealing with these. In between phone calls, the PA Coach will 
continue to send emails to participants on a monthly basis.  These will focus on encouragement toward PA 
goals, encouragements based on data in Fitabase® and personalized tips based on these data.   
Motivational interviewing (MI) principles will be used throughout the PA coaching calls. MI is a key behavior 
change strategy that can elicit participants’ own motivations and / or ambivalence toward PA 81-83.  This helps 
individuals to explore and resolve their own, sometimes conflicting attitudes toward changing PA behaviors, 
building autonomy and internal awareness that is essential for long-term behavior change. To support topics 
discussed during the phone calls, participants will be mailed and/ or emailed materials including: 1) handouts 
describing appropriate exercise for people with osteoarthritis, tips on PA for people with arthritis (including pain 
management), instructions for different types of exercise (aerobic, strengthening, stretching), and example 
exercises. 2) A list of PA programs and resources adapted for their locality. 3) Worksheets for documenting PA 
goals.   
 
Attention Control Intervention  
We chose this type of control group to account for the effect of general attention provided by the PA Coach.  
This group will receive an intervention in the same “dose” (e.g., number and duration of phone calls and 
emails) as the OA-PCP group, but the content will not be PA-specific. During the first call, the Coach will 
discuss 2 topics, for which the amount of content parallels call #1 for the OA-PCP:  What is OA? OA Diagnosis 
and OA Risk Factors.  During the second call, the Coach will discuss the topic of Health Care Providers and 
Overview of OA Treatment Guidelines.  Call topics for 3, 6, 9 and 12- month follow-up calls will be: Pain 
Medications, Mechanical Treatments (e.g., knee braces, footwear, joint protection), Complimentary and 
Alternative Therapies and discussion of OA and Mental Health, Sleep and Fatigue. Participants will be emailed 
or mailed (based on their preference) handouts with information on additional topics related to OA.  The study 
team will ask participants to opt-in to receive follow-up monthly educational emails; if they prefer, they can 
receive this information via mail. 
 
Arthritis 
Foundation 
Online PA Tools 
Resources including arthritis-friendly exercise videos, workouts, tips for 
people with arthritis. COST:  Free 
Group-Based 
Arthritis 
Foundation 
Exercise 
Program 
Community-based exercise program; trained instructors cover a variety of 
range-of-motion and endurance-building activities and health education 
topics.  COST: Free or low cost, varies by location  
Walk with Ease 
(Group-
Delivered) 
Community-based walking program developed by the Arthritis Foundation 
with regular meetings, facilitated by trained leaders.  COST: Typically free 
Fit and Strong 
Community-based PA and behavior change intervention offering 
stretching, balance, and aerobic exercises.  COST: Typically free at Senior 
Centers  
Tai Chi for 
Arthritis 
Group classes available at many YMCAs and other community centers.  
COST: Varies from low cost to free 
Arthritis 
Foundation 
Aquatic Program 
Group classes led by a trained instructor, including joint range of motion, 
breathing, and light aerobic activities. Many community aquatic centers 
have similar, appropriate programs for older adults.  COST: Varies based 
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6.2  
FIDELITY 
PA Coach(es) will be trained by Dr. Allen and will conduct mock sessions of all OA-PCP calls prior to study 
initiation.  We plan to audio record calls for approximately the first 10 participants and a random subset 
thereafter.  Dr. Allen and another investigator with experience in delivering behavioral PA interventions (Dr. 
Callahan or Dr. Golightly) will review audio recordings and provide feedback to the PA Coach.  A similar 
process will be used for the attention control calls, with a particular emphasis on ensuring that OA-PCP content 
is not included in these calls.    
 
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 by clinic site.  
 
6.4  
STUDY INTERVENTION ADHERENCE  
 
The study database will be used to track participants’ completion of all assessment visits, as well as all 
intervention contacts. The coordinator will also maintain close communication with PA coach(es) regarding 
intervention delivery.  If participants miss intervention calls, an unblinded study team member may assist the 
PA coach in attempting to reach the participant. 
 
6.5  
CONCOMITANT THERAPY 
  
Participants will be permitted to continue any other OA treatment during the course of the study.  
 
7  
STUDY INTERVENTION/ DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1  
DISCONTINUATION OF STUDY INTERVENTION 
 
When a participant discontinues from the OA-PCP or attention control intervention but not the study, remaining 
study procedures (e.g., follow-up assessments) will be completed as indicated by the study protocol.  If a 
clinically significant finding is identified after enrollment (e.g. health-related changes that may change the 
safety level of participating in an independent PA program), the investigator or qualified designee will 
determine if any change in participant management is needed. 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. 

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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, 12-month follow-up 
assessment.  If a participant misses intervention calls or follow-up assessments prior to the 12-month time 
point and cannot be contacted during the time frame, the study team will still attempt to contact the participant 
for remaining calls / 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 be 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, 6-months and 12-months by a trained research assistant blinded to 
randomization assignment. Other than the accelerometer, measures will be administered via phone.  
Participants will be paid $25 for completing each phone-based measure and $15 for returning the 
accelerometer device at each time point.   
Primary Efficacy Outcome:  Objectively Assessed Physical Activity.  
We selected this as the primary study outcome because PA is the target of the intervention, and objective 
assessment has advantages over self-report in terms of accuracy 86. Our specific primary outcome of interest 
is minutes of moderate to vigorous intensity PA (MVPA) per week, since this corresponds to DHHS 
recommendations and is a known predictor of outcomes in patients with OA 78. We will also examine step 
counts, minutes of sedentary activity and other complementary metrics, as these are also important for 
providing a broad picture of PA among participants 80,87.  Each participant will be asked to wear the Actigraph 
GT3X+ (Pensacola, FL), which allows for the collection and manipulation of raw actigraphy data to facilitate 
accurate assessment of PA 88.  Participants will be asked to wear the monitors during all waking hours for 7 
days. Following previously established thresholds, outcomes will only be computed for participants who wear 
the accelerometer for 4+ days with 10+ hours of daytime wear. Monitors will be worn on the waist, using either 
an elastic belt or clip, over the right hip.  We may ask a subset of participants to wear a wrist-worn monitor in 
addition to the waist-worn monitor, in order to assess acceptability and compare values obtained from monitors 
worn at the two different sites.  Accelerometers will be mailed with instructions and a pre-stamped / addressed 
return envelope.  Several days after the accelerometer has been mailed, a study team member will call the 
participant to review instructions.  A phone number will be provided for problems or questions. A second call 
will be made toward the end of the 7 days to ask about wear and to remind participants to return the monitor. If 
participants have not worn the monitor enough, they will be asked to wear the monitor a few extra days.  Drs. 
Hales, Callahan and Allen have been involved with projects that have successfully mailed accelerometers to 
and / or from study participants with OA. There have been high rates of adherence (4+ days with 10+ hours of 
wear); 93% in one study of adults and partners with OA and 89% in another of 140 patients with OA, with 

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minimal loss of monitors (< 2%).  In Aim 2 of this project, valid accelerometer data were available for 57 
participants at baseline (95%) and 52 participants at follow-up (86%). Upon return, accelerometer data will be 
downloaded, compiled into 60s epochs, processed to identify wear, non-wear, and sleep periods using current 
algorithms 89,90, and summarized using cut-points developed by Troiano 89 and Mathews 91. These cut-points 
will allow us to calculate minutes of MVPA, as well as sedentary time and step counts.  
Secondary Efficacy Outcomes:  
Self-Reported Physical Function. Physical function is a key outcome in OA and can be improved with regular 
PA 14,15.  We will assess physical function with the widely used Western Ontario and McMaster Universities 
Osteoarthritis Index (WOMAC) subscale 92,93; it includes 17 items, rated on a Likert scale of 0 (no difficulty) to 4 
(extreme difficulty), that assess difficulty with performing a range of daily activities commonly affected by lower 
extremity OA. The reliability and validity of the WOMAC total score and subscales have been confirmed 93.  In 
patients with hip or knee OA, Bellamy et al. reported internal consistency coefficients (Cronbach’s alpha) 
between 0.86 and 0.95 on WOMAC subscales.   
Pain (WOMAC). We will assess self-reported pain using the WOMAC subscale 14,15; it includes 5 items, rated 
on a Likert scale of 0 (no pain) to 4 (extreme pain), that assess pain during a range of daily activities.  
Exploratory Outcomes: 
Stanford Numeric Rating Scale (NRS) for Fatigue: We will assess self-reported fatigue using the Stanford NRS 
Scale for Fatigue; it includes 1 item, rated on a Likert scale of 0 (no fatigue) to 10 (severe fatigue), that 
assesses fatigue in the past 2 weeks.   
 
Self-reported Physical Activity:  Modified version of the CHAMPS (Community Health Activities Model Program 
for Seniors) Physical Activity Measure 94.   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.   
 
Patient Global Impression of Change. We will use this scale to evaluate participants’ perspectives on overall 
changes in their joint pain during the study period. This measure asks participants to describe their change in 
pain on a 7-point rating scale with the following options: “very much improved,” “much improved,” “minimally 
improved,” “no change,” “minimally worse,” “much worse,” and “very much worse.” This scale has been widely 
used in clinical trials of chronic pain and is recommended by IMMPACT. 
 
Pain Medication Use. Pain medications are a common treatment for patients with OA, and some patients seek 
to reduce their use; therefore we have included this as an exploratory outcome.  We will assess pain 
medication use using methods we have used successfully in previous studies.  We will ask participants to bring 
to the telephone all medications (prescription and non-prescription) they are currently taking for their arthritis 
symptoms.  For each medication, the study team will record the medication name, medication class, frequency 
of taking the medication. 
 
PROMIS Sleep Disturbance – Short Form 4a. The PROMIS adult sleep related impairment item bank 
focuses on self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. It 
assesses sleep-related impairment over the past seven days. This scale includes 4 items, each measured on a 
5-point Likert scale. 
 
 
 
 
 

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Potential Mediators and Moderators of Intervention Effects: 
 We are interested in understanding the roles of various “active ingredients” of the OA-PCP (mediators), as 
well as potential patient characteristics that are associated with differential effectiveness (moderators).  With 
respect to mediators, we will assess number of OA-PCP calls completed, participants’ ratings of satisfaction 
and helpfulness of the calls (single item numeric rating scales of 0-10), indicators of whether participants 
engaged with new group-based or self-directed PA resources during the study, and participants’ ratings of 
satisfaction and helpfulness of any new PA resources they have tried. These variables will be assessed at both 
6 and 12 months.  With respect to moderators, we are particularly interested in variables of age, gender and 
level of baseline PA, but we will also conduct additional exploratory analyses of heterogeneity of treatment 
effects, as described below.  
Participant Characteristics:  
We will collect the following information to characterize the study sample: age, race / ethnicity, gender, 
education, works status, marital status, body mass index, comorbid illnesses 95, joints with arthritis symptoms 
and duration of knee / hip OA symptoms, as well as: 
 
Covid-19 Impact Scale. The scale was designed to rate the impact of the COVID-19 pandemic, deferring to 
other well validated scales to assess general stress or symptoms developed in response to the pandemic. This 
scale includes 1 item with the following options: “Reduced my ability to get be physically active a lot”, 
““Reduced my ability to get be physically active a little”, “not affected my ability to be physically active” or 
improved my ability to be physically active”. 
 
Valuing Questionnaire. The Valuing Questionnaire assess the extent of personal values enactment during the 
past-week.  This questionnaire lists 10 life domains (e.g., family relations, physical well-being). Participants 
rate the importance of each domain and how consistently they have lived according to their values in that 
domain during the past week (on a scale of 0–10).   
 
Feasibility and Acceptability: 
The following metrics will inform feasibility: 
• 
Proportion of screened patients who meet the PA eligibility criterion (<150 min per week) 
• 
Proportion of screened patients who are eligible overall  
• 
Proportion of patients who consent to participate, along with refusal reasons for those who do not 
• 
Proportion of participants who complete each phase of the intervention and follow-up assessments  
We have developed open-ended questions to assess acceptability of the intervention. Topics include 
acceptability of each intervention component, usefulness of options provided for PA programs / resources, and 
suggestions for increasing the patient-centeredness of the intervention.  
 
8.2  
SAFETY ASSESSMENTS 
The study PA coach will be trained to deliver the interventions in adherence to and within the scope of the 
intervention.  If a study team member learns of any adverse events (AEs) that occur in the course of 
participants’ home exercise, this will be documented on the Adverse Events form, as described below.  
 
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). 

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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:  
 
• 
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 
The PI or Dr. Nelson or Dr. Golightly (co-investigators on the study) 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 

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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, PI or co-investigator’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 PA Coach 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 

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8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
 
This protocol uses the definition of Unanticipated Problems as defined by the Office for Human Research 
Protections (OHRP). OHRP considers unanticipated problems involving risks to participants or others to 
include, in general, any incident, experience, or outcome that meets all of the following criteria: 
 
(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; 
 
(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.   
 

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8.4.2 UNANTICIPATED PROBLEMS REPORTING 
All UPs will be reported to the NIA and the SO 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.  
 
 
9  
STATISTICAL CONSIDERATIONS 
 
9.1  
STATISTICAL HYPOTHESES 
The aim of this study is to conduct a randomized pilot trial of the refined OA-PCP among n=240 
patients with knee and / or hip OA. Sub-aims and hypotheses are:  
1.  Obtain data on the efficacy of the OA-PCP. 
H1  Participants in OA-PCP intervention will have greater improvement in objectively assessed PA, 
measured at 6 and 12 months, compared to participants in an attention control group.  
H2  Participants in OA-PCP intervention will have greater improvement in self-reported physical function and 
pain, measured at 6 and 12 months, compared to participants in an attention control group. 
2.  Refine the OA-PCP based on feedback from patients, clinic personnel, and community representatives, in 
preparation for a larger, implementation-focused trial.  
 
 
9.2  
SAMPLE SIZE DETERMINATION 
 
We note that this study is an extended 
exploratory phase, in which we are interested 
in obtaining estimates of efficacy that will 
inform a larger trial that is adequately powered 
to detect clinically meaningful differences in 
MVPA. Our sample size was selected on the 
basis of feasibility for this exploratory study and 
involvement of a sufficient number participants 
to adequately assess intervention and study 
procedures. We provide here a description of 
expected statistical power for this sample size. 
Based on previous research on PA 
interventions for OA 98,99, we expect an effect 
size of 0.3-0.7, though have examined a range of possible values from 0.2-0.8 (Table 2).  We also account for 
10% attrition, based on our prior work.  A sample size of 240 participants (120 per group) will provide 
approximately 80% power at 5% level of significance to detect a small-to-medium effect size of 0.38 or greater 
for the difference in minutes of MVPA between intervention and control groups, accounting for expected 
attrition.  
 
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 an 
exploratory trial, the nature of these supportive analyses will be based on observed patterns of intervention 
contacts.  
 
Table 2. Sample size needed based on effect size and study power 
  α=0.05 
Power=80% 
Power=85% 
Power=90% 
Power=95% 
Effect 
size 
Sample 
size 
Sample 
size 
Sample 
size 
Sample 
size 
0.20 
787 
900 
1053 
1301 
0.30 
351 
401 
469 
579 
0.40 
198 
226 
265 
327 
0.50 
128 
146 
170 
210 
0.60 
90 
102 
120 
148 
0.70 
68 
76 
88 
110 
0.80 
52 
60 
68 
84 

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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.   
We hypothesize that participants receiving the OA-PCP will have greater improvement in MVPA compared with 
the attention control group at 6 and 12 months. To determine the effects of the intervention on MVPA, repeated 
measures will be analyzed using linear mixed effects models, with clinic included as a random effect, to 
estimate mean change and 95% confidence intervals in MVPA from baseline to 6-month and 12-month time 
points. This model will account for intra-person clustering for the repeated measures, including a group x time 
effect. We will use the same modeling strategy for continuous secondary and exploratory outcomes.  An 
advantage of this modeling approach is that it uses all available data; participants are not dropped if they miss 
a time point. This approach will reduce the overall amount of missing data and could eliminate the need for 
imputation of missing repeated outcomes 100. However, if we find that missing data are related to measured 
patient factors (i.e., missing not at random [MNAR]), we will carry out sensitivity analyses by imputing missing 
values under the MNAR scenario and examining the results. The SAS procedure PROC MI has several 
options for using multiple imputation in sensitivity analyses based on pattern-mixture models for MNAR data, 
which model the distribution of a response as the mixture of a distribution of the observed responses and a 
distribution of the missing responses 101. Multiple imputation has the advantage of providing a framework for 
incorporating information from these variables, while preserving a parsimonious main treatment effect model 
102,103. Analyses will be conducted on an intent-to-treat basis and carried out using SAS 9.4 (SAS Institute Inc., 
Cary, NC). Tests will be two-sided and considered significant at the 0.05 level. 
Exploration of Mediators.  We are interested in understanding the degree to which various facets of the OA-
PCP contribute to improvements in PA and other outcomes. Because the mediating variables of interest 
(described above) pertain only to the OA-PCP group, our strategy will differ from a traditional mediation 
analysis approach in the context of a clinical trial.  Specifically, we will use linear regression models to assess 
associations between potential mediating variables and outcomes among individuals in the OA-PCP group. 
Each potential mediator will be assessed individually, then we will fit a multivariable model including all 
variables with bivariate associations of p≤0.1.  Analyses will be performed for both 6 and 12 month outcomes. 
Exploration of Moderators. We will explore potential differential treatment effects based on participant 
characteristics, particularly gender, age and baseline PAVS score.  The latter is of interest to help inform the 
inclusion criterion for a larger trial; if individuals with higher baseline PA (though not meeting DHHS 
recommendations) make little additional improvement in PA, we may focus on individuals with lower PA levels 
at screening.  For assessment of differential treatment effects, we will conduct stratified analyses based on 
participant characteristics (e.g., men / women, age categories by decade, quartiles of baseline PAVS scores).  
We propose this strategy because the study is not powered to detect interactions between treatment group and 
participant characteristics. We will also use multivariable logistic regression 104,105  and recursive partitioning 
(RP) 106,107 to explore multidimensional subgroups that exhibit heterogeneous treatment effects; these analyses 
will focus on our a priori characteristics of interest but also explore additional variables.  
 
10  
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 

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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, the study team member will begin the verbal consenting process by phone.  If the 
participant does not have time to complete the verbal consent, the study team member will arrange a date and 
time to call the participant back. No other study activities will occur until this process is completed.   
 
We will use a UNC IRB approved consent form / script with included language that satisfies the HIPAA 
requirements and outlines the protection of health information utilized in the study.   
 
Verbal informed consent and HIPAA authorization will be obtained by a trained study team member.  The study 
team member will read the IRB approved verbal consent script and HIPAA authorization to the potential 
participant and provide an opportunity for him/her to ask any questions that they may have about the research 
study.  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 form and HIPAA authorization 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, the study 
team member will document in REDCap the date verbal consent and the date HIPAA authorization is collected.  
No activities will commence until verbal consent and HIPAA authorization are collected.  Each enrolled 
participant will then be mailed a copy of the consent form and HIPAA authorization to keep for their records.   
 
If after review of 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, 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.   
 
 
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 

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• 
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. 
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. 
 
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 

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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 
David J. Berkoff, MD FAMSSM 
FAAEM 
University of North Carolina at 
Chapel Hill  
University of North Carolina at 
Chapel Hill 
3300 Thurston Bldg, CB #7280 
Chapel Hill, NC  27599-7280 
3142 Bioinformatics Bldg 
Chapel Hill, NC 27599 
919-966-0558 
919-966-7095 
kdallen@med.unc.edu 
david_berkoff@med.unc.edu 
 
 
 
10.1.6 SAFETY OVERSIGHT 
Safety oversight will be under the direction of the NIA 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 monitor the fidelity of intervention delivery as described above.   
 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Quality control (QC) procedures will be implemented as follows: 
 

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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 study measures will be entered directly into the study 
database. If the study database is not accessible, data will be captured on a source document and will ultimately 
be entered 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. 
 
 
 
 
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.   
 
 
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  

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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 NIA and the SO 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 
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 10.1.3. 
 
 
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 National Institute on Aging 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 
 
10.3  ABBREVIATIONS 
 
AE 
Adverse Event 
ATT 
Attention Control  
DHHS 
Department of Health and Human Services 
CCM 
Chronic Care Management  
CMS 
Center for Medicare and Medicaid Services  

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CoC 
Certificate of Confidentiality 
CHAMPS 
Community Health Activities Model Program 
for Seniors 
CFR 
Code of Federal Regulations 
EMR 
Electronic Medical Record 
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 
MOP 
Manual of Procedures 
MI  
Motivational Interviewing  
MVPA 
Moderate to Vigorous Intensity Physical 
Activity 
NIA 
National Institute on Aging 
NIH  
National Institutes of Health 
OA 
Osteoarthritis 
OAAA 
Osteoarthritis Action Alliance  
OARSI 
Osteoarthritis Research Society International  
OA-PCP 
Osteoarthritis Physical activity Care Pathway 
OHRP 
Office for Human Research Protections 
ORBIT 
Obesity-Related Behavioral Intervention 
Trials 
PA 
Physical Activity 
PI 
Principal Investigator 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SO 
Safety Officer 
NRS 
Stanford Numeric Rating Scale  
UNC 
University of North Carolina 
WOMAC 
Western Ontario and McMaster Universities 
Osteoarthritis Index 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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10.4 
PROTOCOL AMENDMENT HISTORY 
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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