Exercise and Steroid in Knee Osteoarthritis

Study Overview
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Brief Summary
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Osteoarthritis (OA) of the knee is a very common chronic joint disorder associated pain and disability. As no cure exists, management aims to reduce pain, improve function, and enhance quality of life. The recommended hierarchy of management should consist of exercise in first line, then the add-on of drugs if necessary, and ultimately, if necessary, surgery. The effect size of exercise therapy is of the same magnitude as most pharmacological treatments but is often without adverse effects. Local pharmacological treatment of the afflicted knee joint is recommended by means of intra-articular injections of corticosteroids, which is considered as a standard medical treatment of knee OA and are included in established guidelines for management of knee OA. While the two treatment approaches have been investigated separately in numerous clinical trials, the efficacy of a combined pharmacological and non-pharmacological approach is not known, despite the high rank of such combined treatment approach on the recommended hierarchy of management. The purpose of this study is to assess the effects of exercise therapy in combination with intra-articular corticosteroid injections on patient reported pain and function in patients with knee OA. The hypothesis is that the combined treatment approach (exercise therapy preceded by intra-articular injection of corticosteroid) enhances the clinical outcome compared to exercise therapy preceded by a placebo injection.

Official Title
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Combined Intra Articular Corticosteroid and Physiotherapeutic Exercise in Patients With Osteoarthritis of the Knee: A Random-ised Clinical Trial

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Drug: Intraarticular steroid
* Drug: Intraarticular saline
* Other: Exercise therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 40 years or above clinical knee osteoarthritis verified by radiography pain during level walking of at least 40 mm on a 0-100 mm visual analog scale clinical signs of local inflammation body mass index between 20 and 35 Exclusion Criteria: Exercise therapy within 3 months Intraarticular corticosteroid within 3 months Counter indications to exercise Counter indications to corticosteroid pregnant or breast feeding Auto immune disease Planned surgery in the study period significant cardiovascular disease significant neuroloigal disease significant psychiatric disease regional pain syndromes (e.g. fibromyalgia) spinal nerve root compression syndromes

Ages Eligible for Study
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Minimum Age: 40 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraarticular steroid + Exercise<br>Intra-articular corticosteroid treatment with subsequent exercise therapy. Exercise therapy is commenced 2 weeks after injection | Drug: Intraarticular steroid<br>* 1 ml methylprednisolon corticosteroid (40 mg Depo-Medrol®) mixed with 4 ml Lidocain (10 mg/ml) without adrenalin. Injections are done ultrasound guided.<br>Other: Exercise therapy<br>* The exercise is commenced 2 weeks after injection. The exercise includes a 10 minute warm up phase (ergometer bicycling) followed by strengthening and coordination exercises focusing on trunk, hip and knees. In case of pain or symptom exacerbation, a rescue exercise program is administered, excluding weight bearing activities.<br>|
| Active Comparator: Intraarticular saline+Exercise<br>Combined intra-articular saline injection and subsequent exercise therapy. Exercise therapy is commenced 2 weeks after injection | Drug: Intraarticular saline<br>* 1 ml isotonic saline mixed with 4 ml Lidocain (10 mg/ml) without adrenalin. Injections are done ultrasound guided<br>Other: Exercise therapy<br>* The exercise is commenced 2 weeks after injection. The exercise includes a 10 minute warm up phase (ergometer bicycling) followed by strengthening and coordination exercises focusing on trunk, hip and knees. In case of pain or symptom exacerbation, a rescue exercise program is administered, excluding weight bearing activities.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee pain | Self-reported pain assessed by the pain subdomain in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire | Change from baseline to week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Knee pain | Self-reported pain assessed by the pain subdomain in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire | Change from baseline to week 2 and week 26 | 
| Knee symptoms | Self-reported knee symptoms, knee related function, quality of life and, function during sports and recreation assessed by the pain subdomain in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire | Change from baseline to week 2, 14, and 26 | 
| Functional pain test | Knee OA pain is associated with movement of the afflicted knee. Therefore we assess pain intensity and movement tolerance during repeated squatting. The test has 3 outcomes: 1) The number of pain free squatting movements that can be done in 30 seconds; 2) the number of painful squatting movements that can be done in 30 seconds; and 3) the average pain intensity during the squatting movements assessed on a 0-10 numeric rating scale. | Change from baseline to week 14, and 26 | 
| Knee Muscle strength | Assessed by an isokinetic dynamometer | Change from baseline to week 14, and 26 | 
| 6 minute walk distance | The distance covered during 6 minutes of fast walking | Change from baseline to week 14, and 26 | 
| Systemic markers of inflammation in blood | Blood sample | Change from baseline to week 14, and 26 | 
| MRI based inflammation | To assess the severity and extent of local inflammation in the knee and surrounding tissues magnetic resonance imaging (MRI) are done before and after intravenous injection of a Gadolinium contrast agent. Contrast agents are only administered to participants with normal kidney function assessed from a standard blood sample | Change from baseline to week 14, and 26 |