Diet and Exercise for Osteoarthritis Prevention

(TOPS Trial)

Recruiting at 3 trial locations

Overseen By Jovita Newman

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Wake Forest University

Disqualifiers: Coronary artery disease, Type 1 diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

1230 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

Is diet and exercise generally safe for humans?

Diet and exercise interventions are generally considered safe for humans, but restrictive dieting can have harmful effects. It's important to focus on developing a healthy lifestyle rather than just weight loss. ^{1 2 3 4 5}

How is the Diet and Exercise treatment for osteoarthritis different from other treatments?

The Diet and Exercise treatment for osteoarthritis is unique because it combines weight loss through dietary changes and physical activity to reduce pain and improve function, targeting inflammation and musculoskeletal health without relying on medication. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment Diet and Exercise, Weight Loss Program, Exercise Therapy, Dietary Intervention for osteoarthritis prevention?

Research shows that combining diet and exercise can lead to significant weight loss and improve symptoms like knee pain and physical function in people with knee osteoarthritis. Weight loss is considered one of the best non-drug ways to slow down the progression of osteoarthritis. ^{7 11 12 13 14}

Who Is on the Research Team?

Stephen P Messier, Ph.D.

Principal Investigator

Wake Forest University

Are You a Good Fit for This Trial?

This trial is for women over 50 with obesity who have no or rare knee pain and no signs of knee osteoarthritis on X-rays or MRI. They must not be using walking aids, have a BMI ≥ 30 kg/m2, and can't be undergoing cancer treatment, have type 1 diabetes, severe heart issues, recent major knee injuries or surgeries.

Inclusion Criteria

I am female.

My knee does not show arthritis on X-ray or MRI.

I rarely have knee pain, less than 15 days a month.

Exclusion Criteria

Blindness

I experience pain in both knees for more than 15 days each month.

I am currently receiving treatment for cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 48-month intervention of dietary weight loss, exercise, and weight-loss maintenance

48 months

Bi-weekly exercise sessions, quarterly group meetings

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diet and Exercise

Trial Overview The study tests if dieting to lose weight combined with exercise can prevent knee osteoarthritis in at-risk women. Participants will either follow this program or join an attention control group. The effects on their knees will be monitored through MRIs and other health measures.

How Is the Trial Designed?

Group I: Diet and Exercise Experimental Treatment 1 Intervention

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.

Group II: Attention Control Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Wake Forest University

Lead Sponsor

Trials

193

Recruited

151,000+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

University of Missouri-Columbia

Collaborator

Trials

387

Recruited

629,000+

Arthritis Foundation

Collaborator

Trials

36

Recruited

46,500+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Office of Research on Women's Health (ORWH)

Collaborator

Trials

34

Recruited

36,300+

Office of Behavioral and Social Sciences Research (OBSSR)

Collaborator

Trials

6

Recruited

8,100+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Office of Disease Prevention

Collaborator

Trials

1

Recruited

1,200+

Rapid Nutrition PLC

Collaborator

Trials

1

Recruited

1,200+

Published Research Related to This Trial

A combined dietary and exercise intervention led to significant weight loss in older obese adults with knee osteoarthritis, with the exercise and diet group losing an average of 18.8 lb (8.5 kg) over 6 months compared to just 4.0 lb (1.8 kg) in the exercise-only group.

Both groups experienced improvements in knee pain, disability, and physical performance, but the combined intervention showed trends suggesting better gait mechanics, indicating potential additional benefits of diet alongside exercise for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and weight loss in obese older adults with knee osteoarthritis: a preliminary study. Messier, SP., Loeser, RF., Mitchell, MN., et al.[2022]

A multi-component dietary weight loss program, including a ketogenic very low calorie diet and video consultations, was well-received by 24 patients with knee osteoarthritis, highlighting its ease of use and convenience as key factors for adherence.

Support from dietitians and the program's holistic approach, which included educational resources and exercise, were crucial for participants' success, leading to improved knee pain and function over the 6-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"It's the single best thing I've done in the last 10 years": a qualitative study exploring patient and dietitian experiences with, and perceptions of, a multi-component dietary weight loss program for knee osteoarthritis. Lawford, BJ., Bennell, KL., Jones, SE., et al.[2021]

In a study of 192 obese patients with knee osteoarthritis, those who received dietary support maintained a greater weight loss (11.0 kg) over one year compared to those in the knee-exercise program (6.2 kg) and control group (8.2 kg), indicating the effectiveness of dietary support in long-term weight management.

All groups experienced significant reductions in knee pain, but there was no difference in pain relief among the groups, suggesting that weight loss alone, regardless of the maintenance program, can improve symptoms of knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial. Christensen, R., Henriksen, M., Leeds, AR., et al.[2022]

In a study of 89 obese patients with knee osteoarthritis, those on an intensive low-energy diet (LED) lost an average of 10.9 kg (11%) over one year, compared to a 3.6 kg (4%) loss in the control group, indicating significant weight loss efficacy (p<0.0001).

While both groups showed improvement in knee osteoarthritis symptoms, the LED group experienced a notable reduction in pain (7.2 mm difference on the WOMAC scale, p=0.022), suggesting that weight loss can lead to meaningful pain relief in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial. Bliddal, H., Leeds, AR., Stigsgaard, L., et al.[2011]

The IDEA trial is a randomized controlled study involving 450 older adults with osteoarthritis, testing the effects of intensive dietary restriction, exercise, or a combination of both over 18 months to see how these interventions impact inflammation and joint loads.

Preliminary results show excellent reliability in measuring knee joint loads and MRI scoring of knee conditions, suggesting that the study's methods are robust and can effectively assess the impact of weight loss on osteoarthritis progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale. Messier, SP., Legault, C., Mihalko, S., et al.[2021]

The ProMuscle in Practice study involves 200 community-dwelling older adults (≥65 years) and evaluates a 24-week combined resistance exercise and nutrition intervention aimed at improving physical functioning and quality of life.

Preliminary insights suggest that this intervention, which includes guided exercise and increased protein intake, may effectively enhance muscle strength and overall physical performance in frail older adults, although results from the ongoing study will provide more definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect, process, and economic evaluation of a combined resistance exercise and diet intervention (ProMuscle in Practice) for community-dwelling older adults: design and methods of a randomised controlled trial. van Dongen, EJI., Haveman-Nies, A., Wezenbeek, NLW., et al.[2023]

Despite the widespread use of diet and exercise interventions to combat obesity, these strategies have shown limited long-term effectiveness, with most individuals experiencing relapse within 3-5 years after initial weight loss.

The paper suggests that future obesity interventions should focus on promoting healthy lifestyles and chronic disease risk reduction rather than solely targeting weight loss, as many popular dieting techniques can be hazardous to health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How effective are traditional dietary and exercise interventions for weight loss? Miller, WC.[2019]

A systematic review of 18 randomized controlled trials found that combining diet and exercise leads to greater long-term weight loss compared to diet alone, with an average additional weight loss of 1.14 kg.

Both diet-only and diet-plus-exercise interventions resulted in some weight regain over time, highlighting the need for future research to develop strategies that promote sustained weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. Wu, T., Gao, X., Chen, M., et al.[2009]

Combining diet and exercise is essential for effective obesity treatment, as neither alone is sufficient; however, very-low-calorie diets can help maintain physical function during significant weight loss.

Long-term success in maintaining weight loss is heavily dependent on adopting regular exercise habits after dieting, highlighting the importance of promoting lifelong exercise practices for sustained weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise during and after very-low-calorie dieting. Phinney, SD.[2018]

In a study of 67 obese adults, both exercise-focused and weight-focused maintenance programs were effective after an initial 6-month weight-loss treatment, but the weight-focused program led to better long-term weight maintenance.

Participants in the weight-focused program reduced their fat consumption more significantly and maintained their weight loss better than those in the exercise-focused program, despite no differences in exercise participation or energy expenditure between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise-focused versus weight-focused maintenance programs on the management of obesity. Leermakers, EA., Perri, MG., Shigaki, CL., et al.[2019]

A combination of diet and exercise treatments significantly reduces pain in overweight and obese adults with knee osteoarthritis, while diet-only treatments do not show a meaningful reduction in pain.

Both diet-only and combined diet and exercise treatments moderately improve physical function, but the effects on inflammatory biomarkers are unclear, with only IL-6 showing a reduction from diet-only treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet-induced weight loss alone or combined with exercise in overweight or obese people with knee osteoarthritis: A systematic review and meta-analysis. Hall, M., Castelein, B., Wittoek, R., et al.[2019]

A systematic review of three trials involving 794 overweight and obese older adults with knee osteoarthritis found that combining physical activity and dietary restriction did not show significant improvements in mobility after 6 months, as indicated by the 6-minute walk test.

Despite the lack of strong evidence from meta-analysis, narrative synthesis suggested that participants in the combined intervention group experienced reductions in body weight and improvements in walking ability compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of physical activity and dietary restriction interventions on weight loss and the musculoskeletal function of overweight and obese older adults with knee osteoarthritis: a systematic review and mixed method data synthesis. Alrushud, AS., Rushton, AB., Kanavaki, AM., et al.[2022]

In a study involving overweight and obese individuals with knee osteoarthritis, changes in systemic inflammation due to diet and exercise accounted for 15% of the reduction in pain and 29% of the improvement in function over 18 months, indicating a significant role of inflammation in managing OA symptoms.

The findings suggest that while changes in body mass index (BMI) contributed minimally to improvements in function, the reduction in inflammatory markers was a strong mediator of both pain relief and functional enhancement, emphasizing the importance of targeting inflammation in OA treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflammatory cytokines mediate the effects of diet and exercise on pain and function in knee osteoarthritis independent of BMI. Runhaar, J., Beavers, DP., Miller, GD., et al.[2020]

The paper outlines a set of best practices for conducting clinical trials focused on lifestyle diet and exercise interventions for osteoarthritis (OA), aimed at both newcomers and experienced researchers in the field.

These recommendations cover essential aspects of trial design, including participant recruitment, study methods, and assessment techniques, providing a comprehensive guide for effective research in OA interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis. Messier, SP., Callahan, LF., Golightly, YM., et al.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Exercise and weight loss in obese older adults with knee osteoarthritis: a preliminary study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

"It's the single best thing I've done in the last 10 years": a qualitative study exploring patient and dietitian experiences with, and perceptions of, a multi-component dietary weight loss program for knee osteoarthritis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial. [2011]

5. England pubmed.ncbi.nlm.nih.gov

The Intensive Diet and Exercise for Arthritis (IDEA) trial: design and rationale. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Effect, process, and economic evaluation of a combined resistance exercise and diet intervention (ProMuscle in Practice) for community-dwelling older adults: design and methods of a randomised controlled trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

How effective are traditional dietary and exercise interventions for weight loss? [2019]

8. England pubmed.ncbi.nlm.nih.gov

Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. [2009]

9. United States pubmed.ncbi.nlm.nih.gov

Exercise during and after very-low-calorie dieting. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Effects of exercise-focused versus weight-focused maintenance programs on the management of obesity. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Diet-induced weight loss alone or combined with exercise in overweight or obese people with knee osteoarthritis: A systematic review and meta-analysis. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Effect of physical activity and dietary restriction interventions on weight loss and the musculoskeletal function of overweight and obese older adults with knee osteoarthritis: a systematic review and mixed method data synthesis. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Inflammatory cytokines mediate the effects of diet and exercise on pain and function in knee osteoarthritis independent of BMI. [2020]

14. England pubmed.ncbi.nlm.nih.gov

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis. [2022]