Footwear and Exercise for Knee Osteoarthritis (FiREwORK Trial)

Study Overview
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Brief Summary
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Osteoarthritis (OA) is a chronic degenerative joint disease and leading cause of musculoskeletal pain and disability worldwide. The high rates of knee replacement surgery worldwide emphasize the need for more effective non-surgical interventions to attenuate progressive disability. International scientific and professional societies also propose that therapies need to seek efficacious combinations of modalities with the ultimate aim to achieve longer-term, optimal and synergistic treatment effects. Exercise therapy, such as strengthening and aerobic exercise, is universally, and strongly, recommended as it demonstrates beneficial effects on clinical symptoms and is considered safe for all patients with knee OA. However, during activities as simple as walking, higher knee joint loads have been demonstrated in people with medial tibiofemoral OA, a common form of knee OA. Increased joint loading as such may elicit aggravated symptoms and accelerated joint structural decline over time. No convincing evidence exists to confirm exercise therapy effectively alters joint loading parameters during walking gait in people with knee OA. Notably, recent studies suggest that wearing appropriate footwear may help offload the joint in people with knee OA, a strategy that is also easily applicable at a wide population level. The purpose of this clinical study is to compare 9-month treatment consisting of exercise therapy and daily wear of one of two shoe classes (flat flexible shoes or stable supportive shoes), on symptom relief and joint structural damage in people with knee OA. In this study, we will randomly allocate eligible participants in one of two treatment arms. This means there will be an equal amount of participants in each group, and participants nor researchers will be able to choose in which group participants will end up in.Participants in both groups will enroll in a 9 month exercise program and will be provided a pair of one of the two shoe classes to wear daily. To ensure an unbiased appraisal of treatment effects, we will not disclose the study hypotheses to participants during the intervention period. The results of this study will help determine whether the addition of appropriate footwear to exercise therapy improves symptom relief and/or slows structural disease progression in people with knee OA.

Official Title
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The FiREwORK Trial - Self-management With FootweaR Combined With Exercise for OsteoaRthritis (OA) at the Knee: a Phase II Randomized Controlled Trial

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Device: Flat Flexible Shoes
* Device: Stable Supportive Shoes
* Other: Exercise Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic and radiographic diagnosis of knee OA as per the American College of Rheumatology criteria (ie, aged≥50, knee pain on most days and osteophytes) Radiographic evidence of medial OA (ie, Kellgren Lawrence(KL) grade ≥2, ≥grade 1 medial joint space narrowing (JSN) (scale 0-3)> lateral JSN, using a standardized atlas) Average knee pain on walking over the past week of ≥4 on a 11-point numeric rating scale (NRS; 0=no pain to 10=worst pain imaginable) Ability to walk unaided Willing to comply with therapy prescriptions Sufficient understanding of the Dutch language Exclusion Criteria: Current and previous (3 months) participation in exercise therapy Current and previous (3 months) use of customised footwear, minimalist shoes, insoles, braces and unable/unwilling to abandon during the study Knee surgery in either knee and/or injections (corticosteroids, hyaluronic acid) in the study knee (most painful knee or right knee if both equally painful) in the past 6 months Current or recent (4 weeks) use of oral corticosteroids Knee replacement or high tibial osteotomy surgery in the past, or planned during the study Inflammatory arthropathies Other muscular, joint, neurological or metabolic conditions affecting lower limb function and/or precluding safe regular participation in exercise therapy and walking Body mass index (BMI) of >36 kg/m2 (due to difficulties performing gait analysis and MRI) Foot/ankle pain/pathologies at either side, and worse than knee pain complaints Contra-indications for radiography & MRI Use of supplements (eg, glucosamine, chondroitin, curcuma derivates) or pain medication (NSAIDs, paracetamol) or other disease modifying or anti-bone resorptive drugs if participants were not on a stable dose for ≥2 months prior to entering the trial

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a mono-centre randomized controlled trial with a 1:1 allocation into the experimental treatment (exercise therapy and Flat Flexible Shoes) and comparator treatment (exercise therapy and Stable Supportive Shoes). Exercise therapy will consist of supervised facility- and home-based exercises for 3 months (primary time point) and unsupervised home-based exercises for a subsequent 6 months (secondary time point).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Flat Flexible Shoes+Exercise Therapy<br>This arm will wear Flat Flexible Shoes daily for the duration of 9 months combined with supervised facility-based and home-based exercise therapy (months 0-3) and unsupervised home-based exercise therapy (months 4-9). | Device: Flat Flexible Shoes<br>* Off-the-shelf commercially available shoes will be used compliant with previously published criteria: (i) heel height <15 mm, (ii) shoe pitch <10 mm, (iii) absent arch support/motion control, (iv) minimal sole rigidity, (v) weight <=200g (+/-10%). Participants will be instructed to wear the shoes at least 4 hours daily for the duration of the 9-month intervention and to avoid wearing other types of shoes, if possible.<br>Other: Exercise Therapy<br>* The 3-month supervised exercise program will consist of one group session per week of approximately 30 minutes complemented with home-based exercises 3 times per week. Group sessions will consist of a 10-min warm-up followed by a circuit training of strengthening and/or neuromuscular exercises. Subsequently, during a 6-month unsupervised home exercise program, participants will perform strengthening exercises of the lower limb muscles 3 times weekly. Throughout the 9-month intervention, participants will be encouraged to maintain a daily routine of aerobic exercises, consisting of structured activity bouts of at least 10 minutes at a moderate intensity (grade 5-6 (out of 10, maximum exertion) on a Rate of Perceived Exertion scale), achieving at least 70 minutes of weekly physical activity at 3 months and 150 minutes at 9 months.<br>|
| Active Comparator: Stable Supportive Shoes+Exercise Therapy<br>This arm will wear Stable Supportive Shoes daily for the duration of 9 months combined with supervised facility-based and home-based exercise therapy (months 0-3) and unsupervised home-based exercise therapy (months 4-9). | Device: Stable Supportive Shoes<br>* Off-the-shelf commercially available shoes will be used compliant with previously published criteria: (i) heel height >30 mm, (ii) shoe pitch >10 mm, (iii) present arch support/motion control, (iv) sole rigidity, (v) weight >300g (+/-10%). Participants will be instructed to wear the shoes at least 4 hours daily for the duration of the 9-month intervention and to avoid wearing other types of shoes, if possible.<br>Other: Exercise Therapy<br>* The 3-month supervised exercise program will consist of one group session per week of approximately 30 minutes complemented with home-based exercises 3 times per week. Group sessions will consist of a 10-min warm-up followed by a circuit training of strengthening and/or neuromuscular exercises. Subsequently, during a 6-month unsupervised home exercise program, participants will perform strengthening exercises of the lower limb muscles 3 times weekly. Throughout the 9-month intervention, participants will be encouraged to maintain a daily routine of aerobic exercises, consisting of structured activity bouts of at least 10 minutes at a moderate intensity (grade 5-6 (out of 10, maximum exertion) on a Rate of Perceived Exertion scale), achieving at least 70 minutes of weekly physical activity at 3 months and 150 minutes at 9 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in severity of knee pain on walking | Scored on an 11-point numeric rating scale for average knee pain on walking over the past week, with terminal descriptors of 0=no pain to 10=worst pain imaginable. | Measured at baseline, 13 and 37 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of intercondylar synovitis | Graded using the MRI Osteoarthritis Knee Score hoffa-synovitis sub-score, ranging grade 0 (normal) to grade 3 (severe). | Measured at baseline, 13 and 37 weeks | 
| Severity of whole knee effusion | Graded using the MRI Osteoarthritis Knee Score effusion-synovitis sub-score, ranging grade 0 (physiologic amount) to grade 3 (large - evidence of capsular distention). | Measured at baseline, 13 and 37 weeks | 
| Severity of bone marrow lesions | Graded using the MRI Osteoarthritis Knee Score bone marrow lesion sub-score, grade 0 (none) to grade 3 (>66% of subregional volume). | Measured at baseline, 13 and 37 weeks | 
| Severity of physical dysfunction | Measured with the function subscale of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. This sub-scale gives a range of possible scores from 0=no dysfunction to 68=maximum dysfunction. | Measured at baseline, 13 and 37 weeks | 
| Severity of knee pain overall | Scored on an 11-point numeric rating scale for average knee pain overall the past week, with terminal descriptors of 0=no pain to 10=worst pain imaginable. | Measured at baseline, 13 and 37 weeks | 
| Participant-perceived global change in pain | Scored on a 7-point ordinal scale (with terminal descriptors of 1=much worse to 7=much better). Participants who report they are moderately better and above will be classified as improved. | Measured at 13 and 37 weeks | 
| Participant-perceived global change in physical function | Scored on a 7-point ordinal scale (with terminal descriptors of 1=much worse to 7=much better). Participants who report they are moderately better and above will be classified as improved. | Measured at 13 and 37 weeks | 
| Participant-perceived global change overall | Scored on a 7-point ordinal scale (with terminal descriptors of 1=much worse to 7=much better). Participants who report they are moderately better and above will be classified as improved. | Measured at 13 and 37 weeks | 
| Average Daily Step Count | Measured using a pedometer attached to the hip for 7 subsequent days to assess objective physical activity. | Measured during weeks 1, 12 and 36 | 
| Habitual physical activity level | Measured using the Physical Activity Scale for the Elderly with scores ranging 0-400 where higher scores indicate greater physical activity. | Measured at baseline, 13 and 37 weeks | 
| Health-related quality of life | Measured using the EuroQoL Quality of Life Scale (EQ-5D) with scores ranging from 0 to 100 (higher scores indication better health-related quality of life). | Measured at baseline, 13 and 37 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee Osteoarthritis, Exercise Therapy, Shoes, Pain