Reducing Obesity and Cartilage Compression in Knees (ROCCK)

OA is a degenerative joint disease that involves the degradation of articular cartilage and underlying subchondral bone. Obesity is identified as a critical and potentially modifiable risk factor for the development and progression of OA. The first objective of the study is to determine the effects of obesity on cartilage composition and function. The second objective of the study is to determine whether weight loss restores cartilage composition and function. Study activities would require getting MR Imaging, evaluation of joint loading using gait analysis techniques, cartilage strain measurement, and participating in weight loss intervention. The study will target a population age group between 18 and 45 years with a BMI greater than or equal to 29. Data analyses will be blinded to reduce potential bias. All subjects participating in this study will be informed of the risks involved and sign an IRB-approved consent form.

Study Overview

• Status: Completed
• Conditions: Obesity; Osteoarthritis; Knee Osteoarthritis
• Intervention / Treatment: Behavioral: Weight Loss

Detailed Description

Appropriate study power will be achieved with 35 participants in the weight loss group and 35 participants in the weight maintenance control group (see Data Analysis and Statistical Considerations). We will recruit and enroll obese (BMI ≥29 - ≤40) men and women, age 18 to 45, with no previous history of lower extremity injury, no evidence of symptoms OA, no knee misalignment (neutral alignment between 178° and 182°), or other injury that would prevent them from performing the walking task required by this study. All inclusion criteria specific to knee injury, OA, and alignment will be verified by MRI scan. All participants in this study will be informed of the risks involved. Upon expressing interest in study participation, participants will be asked questions to determine whether they are free of lower extremity injury and their height and weight will also be recorded to determine their BMI. Potential participants will be pre-screened by phone using a phone script with a list of questions. Once it is determined they meet all study inclusion criteria, they will be invited to attend a consent meeting.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI (BMI ≥29 - <40)
• Age between 18 - 45

Exclusion Criteria:

• History of lower extremity injury
• Evidence of symptoms of knee OA
• Knee misalignment
• Evidence of pregnancy
• Thigh unable to fit in MRI coil
• Body waist fit in MRI
• Have no metals in the body

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Weight-Loss; Participants in the weight-loss intervention arm of the study will be enrolled in an individualized 6-month intervention designed to achieve a 10% reduction of body weight relative to baseline. Each participant receives a calorie (kcal) prescription derived from calculations of estimated total energy expenditure (TEE) based on weight, height, sex, age, and activity level using equations developed by the Institute of Medicine [29]. Prescribed kcal levels are adjusted downward from the TEE to achieve a weekly weight loss of 1 to 2 pounds, generally a deficit of 500-1000 kcal/day. Intervention activities include individual diet counseling, group support, goal setting, self-monitoring, stress management, and problem solving. Weekly group support and education sessions, along with daily food journaling and weekly weigh-ins, are recognized approaches for successful weight loss [30-32]. Once the weight loss goal is achieved, diets will be liberalized for weight maintenance.	Behavioral: Weight Loss; Each participant receives a calorie (kcal) prescription derived from calculations of estimated total energy expenditure (TEE) based on weight, height, sex, age, and activity level using equations developed by the Institute of Medicine [29]. Prescribed kcal levels are adjusted downward from the TEE to achieve a weekly weight loss of 1 to 2 pounds, generally a deficit of 500-1000 kcal/day. Weekly intervention sessions and activities will be delivered virtually using Microsoft Teams, Duke ZOOM or Duke Webex and led by Registered Dietitians.
No Intervention: Wellness Education; Control participants will be counseled to maintain their baseline body weight and level of physical activity. They will report weights weekly and if their weight deviates from baseline they will be asked to keep daily food logs and counseled to return calorie intakes to weight maintenance level. To document diet intakes/adherence, 3-day food records will be collected at months 0, 3, and 6 and analyzed for calorie and nutrient composition. Participants will be encouraged not to change their physical activity levels from baseline and their activity will be monitored by Actigraph activity monitors worn in 7-day periods at months 0, 3, and 6. In addition, each participant will be invited to enter the weight loss intervention after completion of the health education control course.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in cartilage strain/thickness at 3 and 6 months	We will use MRI to detect change in cartilage strain/thickness at 3 and 6 months	Baseline, 3 months, and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in cartilage composition at 3 and 6 months	We will use MRI to detect change in cartilage composition at 3 and 6 months	Baseline, 3 months, and 6 months
Change from baseline in inflammation at 3 and 6 months	Serum and urine biomarkers will be collected to determine levels of inflammation.	Baseline, 3 months, and 6 months
Change from baseline in cartilage degeneration at 3 and 6 months	We will use serum biomarkers to determine cartilage degeneration	Baseline, 3 months, and 6 months
Change from baseline in biomarkers of insulin resistance and beta-cell function at 3 and 6 months	We will use serum biomarkers to determine insulin resistance and beta-cell function	Baseline, 3 months, and 6 months
Change from baseline in muscle strength at 3 and 6 months	Isokinetic dynamometer will be used to determine peak torque of knee extensor and flexor	Baseline, 3 months, and 6 months
Change from baseline in body weight at 3 and 6 months	Body weight as measured by Bodpod	Baseline, 3 months, and 6 months
Change from baseline in fat mass (kg) at 3 and 6 months	Body fat mass (kg) as measured by Bodpod	Baseline, 3 months, and 6 months
Change from baseline in fat mass (%) at 3 and 6 months	Body fat mass (%) as measured by Bodpod	Baseline, 3 months, and 6 months
Change from baseline in lean mass (%) at 3 and 6 months	Body lean mass (%) as measured by Bodpod	Baseline, 3 months, and 6 months
Change from baseline in lean mass (kg) at 3 and 6 months	Body lean mass (%) as measured by Bodpod	Baseline, 3 months, and 6 months
Change from baseline in 6-minute walk (meters) at 3 and 6 months	Distanced (meters) walked in 6 minutes	Baseline, 3 months, and 6 months
Change from baseline in umbilical waist circumference at 3 and 6 months	Body proportions will be measured at the umbilical waist using a Gulick II tape measure with the tape placed directly on the skin (not over clothes). Measurement will be taken once at each location before completing a second measurement, and an average of the two will be recorded. A third measurement will be taken if the first two measurements are >0.5 cm.	Baseline, 3 months, and 6 months
Change from baseline in minimal waist circumference at 3 and 6 months	Body proportions will be measured at the minimal waist using a Gulick II tape measure with the tape placed directly on the skin (not over clothes). Measurement will be taken once at each location before completing a second measurement, and an average of the two will be recorded. A third measurement will be taken if the first two measurements are >0.5 cm.	Baseline, 3 months, and 6 months
Change from baseline in hip circumference at 3 and 6 months	Body proportions will be measured at the hip circumference using a Gulick II tape measure with the tape placed directly on the skin (not over clothes). Measurement will be taken once at each location before completing a second measurement, and an average of the two will be recorded. A third measurement will be taken if the first two measurements are >0.5 cm.	Baseline, 3 months, and 6 months
Change from baseline total calories at 3 and 6 months	Total calories will be measured using a 3-day food record (participant records everything they eat and drink for three days)	Baseline, 3 months, and 6 months
Change from baseline macronutrients at 3 and 6 months	Total calories will be measured using a 3-day food record (participant records everything they eat and drink for three days)	Baseline, 3 months, and 6 months
Change in activity (intensity levels) at 3 and 6 months	Activity intensity levels using an actigraphy device worn for 7 days at each time point	Baseline, 3 months, and 6 months
Change in steps at 3 and 6 months	Steps will be determined using an actigraphy device worn for 7 days at each time point	Baseline, 3 months, and 6 months
Change in Healthy Eating Index at 3 months and 6 months	Healthy Eating Index (HEI-2015) calculated from Dietary History Questionnaire III (DHQIII, National Cancer Institute) at each time point. The HEI score ranges from 0 to 100. An ideal overall HEI score of 100 reflects that the set of foods aligns with key dietary recommendations from the Dietary Guidelines for Americans..	Baseline, 3 months, and 6 months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Lou DeFrate, Duke University

Publications and helpful links

General Publications

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• Messier SP, Gutekunst DJ, Davis C, DeVita P. Weight loss reduces knee-joint loads in overweight and obese older adults with knee osteoarthritis. Arthritis Rheum. 2005 Jul;52(7):2026-32. doi: 10.1002/art.21139.
• Messier SP, Loeser RF, Miller GD, Morgan TM, Rejeski WJ, Sevick MA, Ettinger WH Jr, Pahor M, Williamson JD. Exercise and dietary weight loss in overweight and obese older adults with knee osteoarthritis: the Arthritis, Diet, and Activity Promotion Trial. Arthritis Rheum. 2004 May;50(5):1501-10. doi: 10.1002/art.20256.
• Kopec JA, Rahman MM, Berthelot JM, Le Petit C, Aghajanian J, Sayre EC, Cibere J, Anis AH, Badley EM. Descriptive epidemiology of osteoarthritis in British Columbia, Canada. J Rheumatol. 2007 Feb;34(2):386-93. Epub 2006 Dec 15.
• Goldring SR, Goldring MB. Bone and cartilage in osteoarthritis: is what's best for one good or bad for the other? Arthritis Res Ther. 2010;12(5):143. doi: 10.1186/ar3135. Epub 2010 Oct 19.
• Day JS, Ding M, van der Linden JC, Hvid I, Sumner DR, Weinans H. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage. J Orthop Res. 2001 Sep;19(5):914-8. doi: 10.1016/S0736-0266(01)00012-2.
• Kretzer JP, Jakubowitz E, Sonntag R, Hofmann K, Heisel C, Thomsen M. Effect of joint laxity on polyethylene wear in total knee replacement. J Biomech. 2010 Apr 19;43(6):1092-6. doi: 10.1016/j.jbiomech.2009.12.016. Epub 2010 Jan 13.
• Lahuec C, Almouahed S, Arzel M, Gupta D, Hamitouche C, Jezequel M, Stindel E, Roux C. A self-powered telemetry system to estimate the postoperative instability of a knee implant. IEEE Trans Biomed Eng. 2011 Mar;58(3):822-5. doi: 10.1109/TBME.2010.2069099. Epub 2010 Aug 30.
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• Felson DT, Zhang Y, Anthony JM, Naimark A, Anderson JJ. Weight loss reduces the risk for symptomatic knee osteoarthritis in women. The Framingham Study. Ann Intern Med. 1992 Apr 1;116(7):535-9. doi: 10.7326/0003-4819-116-7-535.
• Abu-Abeid S, Wishnitzer N, Szold A, Liebergall M, Manor O. The influence of surgically-induced weight loss on the knee joint. Obes Surg. 2005 Nov-Dec;15(10):1437-42. doi: 10.1381/096089205774859281. Erratum In: Obes Surg. 2006 Apr;16(4):530. Manor, Orly [added].
• Powell A, Teichtahl AJ, Wluka AE, Cicuttini FM. Obesity: a preventable risk factor for large joint osteoarthritis which may act through biomechanical factors. Br J Sports Med. 2005 Jan;39(1):4-5. doi: 10.1136/bjsm.2004.011841.
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Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2020
• Primary Completion (Actual): October 26, 2023
• Study Completion (Actual): May 17, 2024

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 29, 2021

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: MRI; Arthritis; Knee Health; Weight Loss
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Obesity; Osteoarthritis
• Other Study ID Numbers: Pro00102409

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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