Preventing Posttraumatic Osteoarthritis With Physical Activity Promotion

Osteoarthritis (OA) is a leading cause of disability worldwide that affects millions of Americans each year. Posttraumatic OA (PTOA) significantly impacts patients after anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR) with approximately 50% of patients developing PTOA within 20 years of injury or surgery. Knee joint mechanical loading measured via physical activity (i.e. daily steps) is insufficient in individuals after ACLR compared to uninjured individuals. Establishing the beneficial effects of physical activity to promote optimal free-living knee joint mechanical loading and improve knee joint health will aid in the development of cost-effective interventions that prevent PTOA and health burden of the disease.

Study Overview

• Status: Completed
• Conditions: Arthritis; Joint Diseases; Osteoarthritis; Osteoarthritis, Knee; Anterior Cruciate Ligament Injuries; Knee Injuries; Exercise; Cartilage, Articular
• Intervention / Treatment: Behavioral: Physical Activity Promotion

Detailed Description

Osteoarthritis (OA) is a leading cause of disability worldwide resulting in severe limitations in daily activities and chronic pain. It is estimated that 35% of posttraumatic OA (PTOA) cases occur after knee injuries and surgeries such as anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR). Optimal free-living mechanical loading, which refers to the forces acting on the knee caused by daily activities, plays an essential role in maintaining knee articular cartilage health. After ACLR, individuals take fewer steps per day as compared to uninjured controls. This results in insufficient free-living mechanical loading to joint tissues and is associated with early PTOA development. Adequate physical activity (PA) is recommended to help reduce risk of PTOA, but it is unclear how changes in PA acutely impact knee joint cartilage health. The overall objective of this pretest-posttest experimental pilot study is to determine how optimizing free-living mechanical loading through PA promotion improves cartilage composition in individuals who demonstrate insufficient free-living mechanical loading after ACLR. PA promotion will be delivered over 8 weeks using commercially available PA monitors and the patients' smartphone to provide daily personalized and achievable step goals to increase daily step counts to a level consistent with healthy PA participation. The hypothesis for aim 1 is that MRI markers of proteoglycan density associated with PTOA development will improve after 8-weeks of PA promotion exposure. Hypothesis for aim 2 is that greater changes in steps per day will be associated with improved proteoglycan density. Change in MRI markers of proteoglycan density and steps per day will be assessed using a pretest-posttest design in 8 adults who are 6 months to 5 years post-ACLR with insufficient mechanical loading (<8,000 steps per day)24 and suboptimal quality of life (quality of life survey<87.5). Outcomes will be collected before (pretest) and after (posttest) 8-weeks of PA promotion. For the PA promotion, participants will receive a text message each morning with a personalized, daily step count goal and a link used to confirm receipt of the goal. The preceding 10 days of step data will be rank ordered and the 60th percentile step count will be set as the goal for the next day. The proposed work is innovative, in that this study will use a novel combination of outcomes that will lead to unprecedented insight into the influence of PA promotion in mitigating early PTOA development.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Caroline M Lisee, PhD; Phone Number: 19199622025; Email: liseecar@email.unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Fetzer Hall, University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

Participants will be included if they:

• Provide informed consent and sign a HIPPA form prior to any study procedures are performed
• Have completed all other formal physical therapy and therapeutic exercise regimens, and will not be engaging in any other formal therapy for their ACLR during the study
• Are between the ages of 18 and 35.
• Underwent an ACLR no earlier than 6 months and no later than 5 years prior to enrollment.
• Demonstrate < 8,000 steps per day during the screening phase of the study as assessed using the Actigraph GT9X Link monitor.
• Demonstrate clinically relevant-knee symptoms, defined as a Knee Injury and Osteoarthritis Outcomes Score (KOOS) quality of life subscale < 72.2

Exclusion Criteria

Participants will be excluded if:

• The participant underwent an ACLR revision surgery due to a previous ACL graft injury.
• Multiple ligament surgery was indicated at the time of ACLR surgery.
• A lower extremity fracture was suffered during the ACL injury.
• The participant has been diagnosed with osteoarthritis in either knee
• They have a cochlear implant, metal in body, claustrophobia, or history of seizures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Physical Activity Promotion Group; Participants will receive a text message each morning with a personalized, daily step count goal and a link used to confirm receipt of the goal. The preceding 10 days of step data will be rank ordered and the 60th percentile step count will be set as the goal for the next day.

Behavioral: Physical Activity Promotion; After enrolling, participants will be outfitted with a Fitbit Charge 2 activity monitor. The monitor will be worn during all waking hours, and compliance will be considered as a day with ≥ 1,000 steps. Participants will complete a 14-day "run-in" observation period while wearing the Fitbit but no PA promotion will occur. Individuals who are noncompliant during the "run in" period (<10 days with <1,000 steps) will be removed. Participants will receive a text message each morning with a personalized, daily step count goal and a link used to confirm receipt of the goal. The preceding 10 days of step data will be rank ordered and the 60th percentile step count will be set as the goal for the next day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T1rho Relaxation Times in the Medial Femoral Condyle at Baseline	MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) at pre-intervention (baseline)	pre-intervention (baseline)
T1rho Relaxation Times in the Medial Femoral Condyle Post-intervention	MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) at post-intervention (~8 weeks)	post-intervention (~8 weeks)
T1rho Relaxation Times in the Lateral Femoral Condyle at Baseline	MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e., proteoglycan density) at pre-intervention (baseline)	pre-intervention (baseline)
T1rho Relaxation Times in the Lateral Femoral Condyle Post-intervention	MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e proteoglycan density) at post-intervention (~8 weeks)	post-intervention (~8 weeks)
T1rho Relaxation Times in the Medial Tibial Condyle at Baseline	MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) at pre-intervention (baseline)	pre-intervention (baseline)
T1rho Relaxation Times in the Medial Tibial Condyle Post-intervention	MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) at post-intervention (~8 weeks)	post-intervention (~8 weeks)
T1rho Relaxation Times in the Lateral Tibial Condyle at Baseline	MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) at pre-intervention (baseline)	pre-intervention (baseline)
T1rho Relaxation Times in the Lateral Tibial Condyle Post-intervention	MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) at post-intervention (~8 weeks)	post-intervention (~8 weeks)
Change in Daily Steps	Change in average steps per day over 7 day physical activity monitor wear pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention	pre-intervention (baseline), post-intervention (~8 weeks)
Change in T1rho Relaxation Times in the Medial Femoral Condyle	Change in MRI marker of T1rho relaxation times of medial femoral articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention	pre-intervention (baseline), post-intervention (~8 weeks)
Change in T1rho Relaxation Times in the Medial Tibial Condyle	Change in MRI marker of T1rho relaxation times of medial tibial articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention	pre-intervention (baseline), post-intervention (~8 weeks)
Change in T1rho Relaxation Times in the Lateral Femoral Condyle	change in MRI marker of T1rho relaxation times of lateral femoral articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention	pre-intervention (baseline), post-intervention (~8 weeks)
Change in T1rho Relaxation Times in the Lateral Tibial Condyle	change in MRI marker of T1rho relaxation times of lateral tibial articular cartilage (i.e proteoglycan density) from pre-intervention (baseline) to approximately 8-weeks after physical activity promotion intervention	pre-intervention (baseline), post-intervention (~8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Injury and Osteoarthritis Outcome Score Quality of Life Subscale	Knee injury Osteoarthritis Outcome Score (KOOS) Quality of Life subscale to measure knee-related quality of life at pre-intervention (baseline). A higher score indicates better knee-related quality of life. Min = 0 and Max = 100	pre-intervention (baseline)
Knee Injury and Osteoarthritis Outcome Score Quality of Life Subscale	Knee injury Osteoarthritis Outcome Score Quality of Life subscale (KOOS) Quality of Life subscale to measure knee-related quality of life at post-intervention. A higher score indicates better knee-related quality of life. Min = 0 and Max = 100	post-intervention (~8 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Retained at Post-intervention Visit (~8 Weeks) Physical Activity Promotion Intervention Retention	physical activity promotion intervention retention	post-intervention (~8 weeks)
Percentage of Days Participant is Compliant With Fitbit Monitor Wear (>1,000 Steps Per Day)	physical activity promotion intervention compliance	up to post-intervention (~8 weeks)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: North Carolina Translational and Clinical Sciences Institute
• Investigators: Principal Investigator: Brian Pietrosimone, PhD, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

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• Tudor-Locke C, Craig CL, Brown WJ, Clemes SA, De Cocker K, Giles-Corti B, Hatano Y, Inoue S, Matsudo SM, Mutrie N, Oppert JM, Rowe DA, Schmidt MD, Schofield GM, Spence JC, Teixeira PJ, Tully MA, Blair SN. How many steps/day are enough? For adults. Int J Behav Nutr Phys Act. 2011 Jul 28;8:79. doi: 10.1186/1479-5868-8-79.
• Roos EM, Toksvig-Larsen S. Knee injury and Osteoarthritis Outcome Score (KOOS) - validation and comparison to the WOMAC in total knee replacement. Health Qual Life Outcomes. 2003 May 25;1:17. doi: 10.1186/1477-7525-1-17.
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• Ingelsrud LH, Granan LP, Terwee CB, Engebretsen L, Roos EM. Proportion of Patients Reporting Acceptable Symptoms or Treatment Failure and Their Associated KOOS Values at 6 to 24 Months After Anterior Cruciate Ligament Reconstruction: A Study From the Norwegian Knee Ligament Registry. Am J Sports Med. 2015 Aug;43(8):1902-7. doi: 10.1177/0363546515584041. Epub 2015 May 14.
• Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, Dragomir A, Kalsbeek WD, Luta G, Jordan JM. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 2008 Sep 15;59(9):1207-13. doi: 10.1002/art.24021.
• Nelson AE, Allen KD, Golightly YM, Goode AP, Jordan JM. A systematic review of recommendations and guidelines for the management of osteoarthritis: The chronic osteoarthritis management initiative of the U.S. bone and joint initiative. Semin Arthritis Rheum. 2014 Jun;43(6):701-12. doi: 10.1016/j.semarthrit.2013.11.012. Epub 2013 Dec 4.
• Luc B, Gribble PA, Pietrosimone BG. Osteoarthritis prevalence following anterior cruciate ligament reconstruction: a systematic review and numbers-needed-to-treat analysis. J Athl Train. 2014 Nov-Dec;49(6):806-19. doi: 10.4085/1062-6050-49.3.35.
• Hurley JC, Hollingshead KE, Todd M, Jarrett CL, Tucker WJ, Angadi SS, Adams MA. The Walking Interventions Through Texting (WalkIT) Trial: Rationale, Design, and Protocol for a Factorial Randomized Controlled Trial of Adaptive Interventions for Overweight and Obese, Inactive Adults. JMIR Res Protoc. 2015 Sep 11;4(3):e108. doi: 10.2196/resprot.4856.
• Roos EM, Roos HP, Ekdahl C, Lohmander LS. Knee injury and Osteoarthritis Outcome Score (KOOS)--validation of a Swedish version. Scand J Med Sci Sports. 1998 Dec;8(6):439-48. doi: 10.1111/j.1600-0838.1998.tb00465.x.
• Furner SE, Hootman JM, Helmick CG, Bolen J, Zack MM. Health-related quality of life of US adults with arthritis: analysis of data from the behavioral risk factor surveillance system, 2003, 2005, and 2007. Arthritis Care Res (Hoboken). 2011 Jun;63(6):788-99. doi: 10.1002/acr.20430.
• Alkan BM, Fidan F, Tosun A, Ardicoglu O. Quality of life and self-reported disability in patients with knee osteoarthritis. Mod Rheumatol. 2014 Jan;24(1):166-71. doi: 10.3109/14397595.2013.854046.
• Brown TD, Johnston RC, Saltzman CL, Marsh JL, Buckwalter JA. Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma. 2006 Nov-Dec;20(10):739-44. doi: 10.1097/01.bot.0000246468.80635.ef.
• Andriacchi TP, Mundermann A. The role of ambulatory mechanics in the initiation and progression of knee osteoarthritis. Curr Opin Rheumatol. 2006 Sep;18(5):514-8. doi: 10.1097/01.bor.0000240365.16842.4e.
• Bell DR, Pfeiffer KA, Cadmus-Bertram LA, Trigsted SM, Kelly A, Post EG, Hart JM, Cook DB, Dunn WR, Kuenze C. Objectively Measured Physical Activity in Patients After Anterior Cruciate Ligament Reconstruction. Am J Sports Med. 2017 Jul;45(8):1893-1900. doi: 10.1177/0363546517698940. Epub 2017 Apr 18.
• Palmieri-Smith RM, Cameron KL, DiStefano LJ, Driban JB, Pietrosimone B, Thomas AC, Tourville TW, Consortium ATO. The Role of Athletic Trainers in Preventing and Managing Posttraumatic Osteoarthritis in Physically Active Populations: a Consensus Statement of the Athletic Trainers' Osteoarthritis Consortium. J Athl Train. 2017 Jun 2;52(6):610-623. doi: 10.4085/1062-6050-52.2.04.
• Pfeiffer S, Harkey MS, Stanley LE, Blackburn JT, Padua DA, Spang JT, Marshall SW, Jordan JM, Schmitz R, Nissman D, Pietrosimone B. Associations Between Slower Walking Speed and T1rho Magnetic Resonance Imaging of Femoral Cartilage Following Anterior Cruciate Ligament Reconstruction. Arthritis Care Res (Hoboken). 2018 Aug;70(8):1132-1140. doi: 10.1002/acr.23477. Epub 2018 Jul 4.
• Pietrosimone B, Nissman D, Padua DA, Blackburn JT, Harkey MS, Creighton RA, Kamath GM, Healy K, Schmitz R, Driban JB, Marshall SW, Jordan JM, Spang JT. Associations between cartilage proteoglycan density and patient outcomes 12months following anterior cruciate ligament reconstruction. Knee. 2018 Jan;25(1):118-129. doi: 10.1016/j.knee.2017.10.005. Epub 2018 Jan 9.
• Salavati M, Akhbari B, Mohammadi F, Mazaheri M, Khorrami M. Knee injury and Osteoarthritis Outcome Score (KOOS); reliability and validity in competitive athletes after anterior cruciate ligament reconstruction. Osteoarthritis Cartilage. 2011 Apr;19(4):406-10. doi: 10.1016/j.joca.2011.01.010. Epub 2011 Jan 19.
• Xu X, Tupy S, Robertson S, Miller AL, Correll D, Tivis R, Nigg CR. Successful adherence and retention to daily monitoring of physical activity: Lessons learned. PLoS One. 2018 Sep 20;13(9):e0199838. doi: 10.1371/journal.pone.0199838. eCollection 2018.
• Adams MA, Sallis JF, Norman GJ, Hovell MF, Hekler EB, Perata E. An adaptive physical activity intervention for overweight adults: a randomized controlled trial. PLoS One. 2013 Dec 9;8(12):e82901. doi: 10.1371/journal.pone.0082901. eCollection 2013.
• Kuenze C, Lisee C, Pfeiffer KA, Cadmus-Bertram L, Post EG, Biese K, Bell DR. Sex differences in physical activity engagement after ACL reconstruction. Phys Ther Sport. 2019 Jan;35:12-17. doi: 10.1016/j.ptsp.2018.10.016. Epub 2018 Oct 26.
• Kuenze C, Cadmus-Bertram L, Pfieffer K, Trigsted S, Cook D, Lisee C, Bell D. Relationship Between Physical Activity and Clinical Outcomes After ACL Reconstruction. J Sport Rehabil. 2019 Feb 1;28(2):180-187. doi: 10.1123/jsr.2017-0186. Epub 2018 Oct 15.
• Lisee CM, Montoye AHK, Lewallen NF, Hernandez M, Bell DR, Kuenze CM. Assessment of Free-Living Cadence Using ActiGraph Accelerometers Between Individuals With and Without Anterior Cruciate Ligament Reconstruction. J Athl Train. 2020 Sep 1;55(9):994-1000. doi: 10.4085/1062-6050-425-19.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Actual): September 9, 2022
• Study Completion (Actual): September 9, 2022

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Leg Injuries; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Wounds and Injuries; Anterior Cruciate Ligament Injuries; Joint Diseases; Knee Injuries
• Other Study ID Numbers: 21-0614; 2KR1372103 (Other Grant/Funding Number: North Carolina Translational and Clinical Sciences Institute)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: 9 to 36 months
• IPD Sharing Access Criteria: The investigator who proposes to use the data has approval from an IRB, IEC, or REB, as applicable, and an executed data use/sharing agreement with UNC.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No