The Osteoarthritis Prevention Study

NCT ID: NCT05946044

Last Updated: 2025-07-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

1230 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-21

Study Completion Date

2029-07-31

Brief Summary

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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

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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

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Osteoarthritis, Knee

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors
assessor-blinded

Study Groups

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Attention Control

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Diet and Exercise

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 Type EXPERIMENTAL

Diet and Exercise

Intervention Type BEHAVIORAL

Group and individual weight loss and weight maintenance sessions combined with exercise throughout the 48 months.

Interventions

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Diet and Exercise

Group and individual weight loss and weight maintenance sessions combined with exercise throughout the 48 months.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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

NIH

Sponsor Role collaborator

Arthritis Foundation

OTHER

Sponsor Role collaborator

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role collaborator

Office of Disease Prevention

UNKNOWN

Sponsor Role collaborator

Office of Research on Women's Health (ORWH)

NIH

Sponsor Role collaborator

Office of Behavioral and Social Sciences Research (OBSSR)

NIH

Sponsor Role collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role collaborator

University of Missouri-Columbia

OTHER

Sponsor Role collaborator

Rapid Nutrition PLC

UNKNOWN

Sponsor Role collaborator

Wake Forest University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stephen P Messier, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Wake Forest University

Winston-Salem, North Carolina, United States

Site Status RECRUITING

University of Sydney

Sydney, , Australia

Site Status RECRUITING

Countries

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United States Australia

Central Contacts

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Jovita Newman

Role: CONTACT

336-758-3969

Facility Contacts

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Paul Oh

Role: primary

617-525-8349

Cortney Armitano-Lago

Role: primary

919-962-2025

Jovita Newman

Role: primary

336-758-3969

Frances Daley

Role: primary

+61 434 023 970

Karen Bracken

Role: backup

+61 2 9926 4928

References

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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.

Reference Type BACKGROUND
PMID: 38144515 (View on PubMed)

Other Identifiers

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U01AR082121-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00080136

Identifier Type: -

Identifier Source: org_study_id

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