An interventional study of Diet and Exercise in Osteoarthritis, Knee, sponsored by Wake Forest University. Recruiting at 4 sites in 2 countries. Open to female participants aged 50 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-23.
Sponsored by Wake Forest University · Not applicable, Interventional, and Prevention
The goal of this study is to establish the efficacy of an intervention of dietary weight loss, exercise, and weight-loss maintenance for knee Osteoarthritis (OA) prevention in adult females aged ≥ 50 years with obesity and no or infrequent knee pain. The primary aim is to compare the effects of a dietary weight loss, exercise, and weight-loss maintenance to an attention control group in preventing the development of structural Magnetic Resonance Imaging (MRI) knee OA. Secondary aims will determine the intervention effects on pain, mobility, health-related quality of life, knee joint compressive forces, inflammatory measures, weight loss, exercise self-efficacy, and cost-effectiveness of this intervention.
Osteoarthritis (OA), the leading cause of disability among adults, is without a cure and is associated with significant comorbidities. OA ranks as the third most common diagnosis for hospital inpatient stays with 1.25 M per year, with the knee the most commonly affected weight-bearing joint. This study will address knee OA disease prevention in adult females because prevention of OA is preferable to treatment, females are affected at nearly twice the rate as males, and to date interventions designed to slow or stop knee OA progression have failed. Dietary weight loss, with and without exercise, has level 1 evidence of effective treatment for adults with knee OA and overweight and obesity. Reduced degenerative cartilage changes are also associated with weight loss, making it a possible preventive therapy for people at risk for knee OA. The objective of this Phase III, multi-site (Boston, MA, Chapel Hill, NC, Sydney, Australia, and Winston-Salem, NC) randomized clinical trial is to establish the efficacy of an intervention of dietary weight loss, exercise, and weight-loss maintenance for knee OA prevention. We will establish efficacy in structural, symptomatic, and mechanistic outcomes compared to attention control, and determine the cost-effectiveness of this non-pharmacologic, non-surgical intervention in preventing incident knee OA in adult females aged ≥ 50 years with obesity and no or infrequent knee pain, a cohort at high risk for knee OA.
Participants will be 1,230 ambulatory, community dwelling females with obesity (BMI ≥ 30 kg/m2), and aged ≥ 50 years. Structural and symptomatic eligibility will be determined at the individual knee level. The eligible knee will have no radiographic (Kellgren Lawrence (KL) score ≤ 1) and no MRI knee OA with no or infrequent knee pain (\< 15 days/month) in the same knee. The primary aim is to compare the effects of a 48-month intervention of dietary weight loss, exercise, and weight-loss maintenance to an attention control group in preventing the development of structural (MRI) knee OA using the MRI OA Knee Score (MOAKS). Secondary aims will determine the intervention effects on the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain, mobility (6 minute walk distance), and health-related quality of life (SF-36). Mechanistic secondary outcomes include knee joint compressive forces as a measure of joint loading, IL-6 as an inflammatory measure, and weight loss and exercise self-efficacy. A cost-effectiveness analysis will establish the value of the 48-month D+E (diet and exercise) intervention.
This study is significant in that it will test a critically needed primary prevention intervention of dietary weight loss, exercise, and weight-loss maintenance for females at risk for the development of knee OA designed to reduce incident structural knee OA compared to an attention control group, and intended to maximize health benefits at a reasonable cost.
3,292 studies on the registry are indexed under Osteoarthritis, Knee; 623 are open to participants now.
This study's planned enrollment of 1,230 is above the median of 68 across 2,714 interventional studies indexed under Osteoarthritis, Knee.
Browse Osteoarthritis, Knee studies →Wake Forest University is the lead sponsor of 118 studies on the registry; 7 are open to participants now.
Of its 31 completed or terminated interventional studies of FDA-regulated products, 27 (87%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
This comparison group provides attention, social interaction, and healthy lifestyle classes. There will be 4, 1-hour face-to-face group meetings per year featuring community health professionals, quarterly newsletters, and quarterly text messages.
The dietary component of the weight loss intervention is characterized by the frequency of contacts, methods to induce dietary restriction, and behavioral therapy strategies. The first 6 months of the diet program is an energy-restricted diet with the option of using partial meal replacements and nutritious snacks (Rapid Nutrition, PLC). The weight loss goal for the diet and exercise group is a minimum of 10% of baseline body weight by the end of year 1. The weight loss phase is followed by 3 years of a weight-loss maintenance program, with the goal of sustaining the achieved weight loss. The exercise component includes 60-minute sessions 2 days per week for 48 months.
Behavioral: Diet and Exercise
Group and individual weight loss and weight maintenance sessions combined with exercise throughout the 48 months.
Structural knee Osteoarthritis (OA) MRI change Scores
Compare the effects of a 48-month intervention of dietary weight loss, exercise, and weight-loss maintenance to an attention control group in preventing the development of structural (MRI) knee OA. Assessed using the MRI Osteoarthritis Knee Score (MOAKS). The MOAKS evaluates degenerative changes in the knee, including the location and severity of osteophyte formation, bone marrow lesions, and cartilage loss. The MOAKS classification system of osteophytes has grades ranging from 0 (none) to 3 (large).
Time frame: Month 48
Knee Pain Scores
Compare the effects of a 48-month intervention of dietary weight loss, exercise and weight-loss maintenance to an attention control group on the Knee Injury and Osteoarthritis Outcome Score (KOOS pain). Standardized answer options are given (5 Likert boxes) and each question is assigned a score from 0 to 4. A normalized score is calculated for the pain subscale. We will transform the score to a 0-100 scale, with 100 representing the most pain and 0 representing no pain.
Time frame: Month 48
Mobility Scores
Compare the effects of a 48-month intervention of dietary weight loss, exercise and weight-loss maintenance to an attention control group on 6-minute walk distance. Assessment of 6 minute walk distance (measured in meters). Greater distance indicates better mobility.
Time frame: Month 48
Health-Related Quality of Life Scores
Compare the effects of a 48-month intervention of dietary weight loss, exercise and weight-loss maintenance to an attention control group on health-related quality of life (SF-36). Questions from the SF-36 yield 2 broad summary scores: physical health and mental health. Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state.
Time frame: Month 48
Knee Joint Loading Number
Compare the effects of a 48-month intervention of dietary weight loss, exercise, and weight-loss maintenance to an attention control group on knee joint compressive loads (Newtons). Higher numbers indicate greater loads.
Time frame: Month 48
Inflammation Value
Compare the effects of a 48-month intervention of dietary weight loss, exercise, and weight-loss maintenance to an attention control group on plasma Interleukin-6 (IL-6). Higher values indicate more inflammation.
Time frame: Month 48
Self-Efficacy Scores - exercise
Compare the effects of a 48-month intervention of dietary weight loss, exercise, and weight-loss maintenance to an attention control group on exercise self-efficacy. Exercise self efficacy will be measured using the walking efficacy for duration scale measures one's ability to walk/jog at a moderately fast pace for various durations. Range 0-100. A higher score indicates a higher self-efficacy. indicate better self-efficacy.
Time frame: Month 48
Self-Efficacy Scores - weight loss
Compare the effects of a 48-month intervention of dietary weight loss, exercise, and weight-loss maintenance to an attention control group on weight loss self-efficacy. Weight-loss self efficacy will be measured by the weight efficacy lifestyle questionnaire. A 20-item measure developed to assess self-efficacy for weight management. Participants are asked to rate their confidence to resist the desire to eat using a 10-point scale ranging from 0 not confident to 9 very confident. Total scores range from 0-180. Higher scores indicate better self-efficacy.
Time frame: Month 48
Cost-Effectiveness Ratios
To establish the cost-effectiveness of this multimodal weight loss, exercise, and weight-loss maintenance program by conducting cost-effectiveness and budgetary impact analyses using data from the current trial in a validated computer-simulation model of knee OA. The cost-effectiveness ratio provides a measure of value for money. The cost-effectiveness of a specific prevention or treatment strategy is measured in dollars per quality-adjusted life-year gained ($/QALY). a budget impact analysis (BIA) of the weight loss program quantifies the financial consequences of adopting the weight loss program by various payer models.
Time frame: Month 48
Not enrolling at this site.
Plan to share: Yes — All of the individual participant data collected during the trial after deidentification.
Supporting information: Study protocol, Informed consent form, Clinical study report
Time frame: Immediately following publication. No end date.
Access criteria: Investigators whose proposed use of the data has been approved by the study P\&P committee. Proposals should be directed to the study PI, Stephen Messier at messier@wfu.edu or the central contact.
Started Mar 2024 (actual). Primary completion is estimated for Jul 2029, 64 months after the start.
Of 1,111 non-industry interventional studies with no phase under Osteoarthritis, Knee, half reached primary completion within 18 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 36. This study's planned 64 months is above that.
Counting every sponsor, half of 1,251 studies reached it within 18 months; a quarter within 8 and three quarters within 36.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.