Reducing Obesity and Cartilage Compression in Knees (ROCCK)

• ClinicalTrials.gov Identifier: NCT04730557
• Recruitment Status: Recruiting
• First Posted: January 29, 2021
• Last Update Posted: August 11, 2021
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Obesity; Osteoarthritis; Knee Osteoarthritis	Behavioral: Weight Loss	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Reducing Obesity and Cartilage Compression in Knees
• Actual Study Start Date: June 5, 2020
• Estimated Primary Completion Date: May 31, 2023
• Estimated Study Completion Date: May 31, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in cartilage strain/thickness at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   We will use MRI to detect change in cartilage strain/thickness at 3 and 6 months

Secondary Outcome Measures :

1. Change from baseline in cartilage composition at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   We will use MRI to detect change in cartilage composition at 3 and 6 months
2. Change from baseline in inflammation at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   Serum and urine biomarkers will be collected to determine levels of inflammation.
3. Change from baseline in cartilage degeneration at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   We will use serum biomarkers to determine cartilage degeneration
4. Change from baseline in biomarkers of insulin resistance and beta-cell function at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   We will use serum biomarkers to determine insulin resistance and beta-cell function
5. Change from baseline in muscle strength at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   Isokinetic dynamometer will be used to determine peak torque of knee extensor and flexor
6. Change from baseline in body weight at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   Body weight as measured by Bodpod
7. Change from baseline in fat mass (kg) at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   Body fat mass (kg) as measured by Bodpod
8. Change from baseline in fat mass (%) at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   Body fat mass (%) as measured by Bodpod
9. Change from baseline in lean mass (%) at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
   Body lean mass (%) as measured by Bodpod
10. Change from baseline in lean mass (kg) at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
    Body lean mass (%) as measured by Bodpod
11. Change from baseline in 6-minute walk (meters) at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
    Distanced (meters) walked in 6 minutes
12. Change from baseline in umbilical waist circumference at 3 and 6 months [ Time Frame: Baseline, 3 months, 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.
13. Change from baseline in minimal waist circumference at 3 and 6 months [ Time Frame: Baseline, 3 months, 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.
14. Change from baseline in hip circumference at 3 and 6 months [ Time Frame: Baseline, 3 months, 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.
15. Change from baseline total calories at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
    Total calories will be measured using a 3-day food record (participant records everything they eat and drink for three days)
16. Change from baseline macronutrients at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
    Total calories will be measured using a 3-day food record (participant records everything they eat and drink for three days)
17. Change in activity (intensity levels) at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
    Activity intensity levels using an actigraphy device worn for 7 days at each time point
18. Change in steps at 3 and 6 months [ Time Frame: Baseline, 3 months, and 6 months ]
    Steps will be determined using an actigraphy device worn for 7 days at each time point
19. Change in Healthy Eating Index at 3 months and 6 months [ Time Frame: Baseline, 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..

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Amir Hakim, BS; 919-660-7507; amir.hakim@duke.edu

Locations

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: Amir Hakim, BS 919-660-7507 amir.hakim@duke.edu

Sponsors and Collaborators

Duke University

Investigators

• Principal Investigator: Lou DeFrate; Duke University

More Information

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• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT04730557
• Other Study ID Numbers: Pro00102409
• First Posted: January 29, 2021
• Last Update Posted: August 11, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Duke University:

Weight Loss; MRI; Arthritis; Knee Health

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases