Osteoarthritis, KneeTOPSNCT05946044
The Osteoarthritis Prevention Study
A study testing Diet and Exercise in people with Osteoarthritis, Knee, run by Wake Forest University at 4 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- Diet and Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,230 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 21 Mar 2024to 31 Jul 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Female
- BMI ≥ 30 kg/m2
- An eligible knee will have no OA by xray and MRI
- No or infrequent knee pain (< 15 days/month) in the same knee
Who cannot join
- symptomatic or severe coronary artery disease
- unable to walk without a device
- blindness
- type 1 diabetes
- active treatment for cancer
- during the past 12 months knee fracture, anterior cruciate ligament (ACL), medial collateral ligament (MCL), or meniscus injury with or without surgical repair
Show all 17Show fewer
- knee injection during the past 6 months
- bilateral knee OA by x-ray Kellgren-Lawrence (KL) ≥ 2
- bilateral knee OA by MRI
- bilateral symptomatic knee OA (frequent bilateral knee pain > 15 days per month)
- BMI< 30.0 kg/m2
- male sex
- claustrophobia
- contraindication to MRI including body weight > 300 lbs or knee coil does not fit
- unwillingness or inability to change eating and physical activity habits due to environment
- cannot speak and read English
- planning to leave area > 2 months during the 48-month intervention period
Trial locations and contacts
4 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
4 sites in 2 countries
United States3 sites, 2 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Paul Oh, 617-525-8349, paoh@bwh.harvard.edu
Elena Losina, Ph.D.
- Active, not recruiting
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27516
- Recruiting
Wake Forest University
Winston-Salem, North Carolina, 27109
Jovita Newman, 336-758-3969, jollajk@wfu.edu
Shannon Mihalko, Ph.D.
Australia1 site, 1 recruiting
- Recruiting
University of Sydney
Sydney
Frances Daley, +61 434 023 970, frances.daley@sydney.edu.au
Karen Bracken, +61 2 9926 4928, karen.bracken@sydney.edu.au
About this study
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.
Read the detailed description
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.
- Conditions
- Osteoarthritis, Knee
- Being tested
- Diet and Exercise
- Keywords
- Obesity, Knee Pain
- Medical subject headings
- Osteoarthritis, Knee, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diet and ExerciseBehavioural
Group and individual weight loss and weight maintenance sessions combined with exercise throughout the 48 months.
| Study group | Role | What they receive |
|---|---|---|
| Attention Control | No 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. |
| Diet and Exercise | Experimental | 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. Receives: Behavioral: Diet and Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Month 48
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Month 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2023
- Study start21 Mar 2024
- Primary completion31 Jul 2029 (estimated)
- Study completion31 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wake Forest University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Arthritis Foundation, National Center for Complementary and Integrative Health (NCCIH), Office of Disease Prevention, Office of Research on Women's Health (ORWH), Office of Behavioral and Social Sciences Research (OBSSR), Centers for Disease Control and Prevention, University of Missouri-Columbia, Rapid Nutrition PLC
- Responsible party
- Sponsor
- Investigators
- Stephen P Messier, Ph.D., Principal investigator, Wake Forest University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05946044
- Sponsor's protocol ID
- IRB00080136
- Other IDs
- U01AR082121-01
- Acronym
- TOPS
- Status last verified
- Jul 2026
- First submitted
- 6 Jul 2023
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial after deidentification.
Publications
Messier SP, Callahan LF, Losina E, Mihalko SL, Guermazi A, Ip E, Miller GD, Katz JN, Loeser RF, Pietrosimone BG, Soto S, Cook JL, Newman JJ, DeVita P, Spindler KP, Runhaar J, Armitano-Lago C, Duong V, Selzer F, Hill R, Love M, Beavers DP, Saldana S, Stoker AM, Rice PE, Hunter DJ. The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis: Design and rationale. Osteoarthr Cartil Open. 2023 Nov 20;6(1):100418. doi: 10.1016/j.ocarto.2023.100418. eCollection 2024 Mar.
PubMed 38144515
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Osteoarthritis Prevention Study
- ClinicalTrials.gov ID
- NCT05946044
- Acronym / sponsor ID
- TOPS / IRB00080136
- Conditions
- Osteoarthritis, Knee
- Keywords
- Obesity, Knee Pain
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,230 participants (estimated)
- Lead sponsor
- Wake Forest UniversityUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Arthritis Foundation, National Center for Complementary and Integrative Health (NCCIH), Office of Disease Prevention, Office of Research on Women's Health (ORWH), Office of Behavioral and Social Sciences Research (OBSSR), Centers for Disease Control and Prevention, University of Missouri-Columbia, Rapid Nutrition PLC
- Study start
- 21 Mar 2024 (actual)
- Primary completion
- 31 Jul 2029 (estimated)
- Study completion
- 31 Jul 2029 (estimated)
- First posted
- 14 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Attention Control | No 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. |
| Diet and Exercise | Experimental | Behavioral: Diet and ExerciseThe 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. |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Female
- BMI ≥ 30 kg/m2
- An eligible knee will have no OA by xray and MRI
- No or infrequent knee pain (< 15 days/month) in the same knee
Key exclusion criteria (17 listed)
- symptomatic or severe coronary artery disease
- unable to walk without a device
- blindness
- type 1 diabetes
- active treatment for cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Diet and ExerciseGroup and individual weight loss and weight maintenance sessions combined with exercise throughout the 48 months. | Behavioural | Diet and Exercise |
Primary outcome
Structural knee Osteoarthritis (OA) MRI change Scores
Time frame: Month 48
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).
3 secondary outcomes
Knee Pain Scores
Time frame: Month 48
Mobility Scores
Time frame: Month 48
Health-Related Quality of Life Scores
Time frame: Month 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
- Background: PubMed 38144515Messier SP, Callahan LF, Losina E, Mihalko SL, Guermazi A, Ip E, Miller GD, Katz JN, Loeser RF, Pietrosimone BG, Soto S, Cook JL, Newman JJ, DeVita P, Spindler KP, Runhaar J, Armitano-Lago C, Duong V, Selzer F, Hill R, Love M, Beavers DP, Saldana S, Stoker AM, Rice PE, Hunter DJ. The osteoarthritis prevention study (TOPS) - A randomized controlled trial of diet and exercise to prevent Knee Osteoarthritis: Design and rationale. Osteoarthr Cartil Open. 2023 Nov 20;6(1):100418. doi: 10.1016/j.ocarto.2023.100418. eCollection 2024 Mar.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial after deidentification.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Stephen P Messier, Ph.D. principal investigator
Wake Forest University
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Diet and Exercise in people with Osteoarthritis, Knee, run by Wake Forest University at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jovita Newman (336-758-3969, jollajk@wfu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Structural knee Osteoarthritis (OA) MRI change Scores (time frame: Month 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05946044, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.