Aerobic vs Neuromuscular Exercise for Knee OA

Study Overview
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Brief Summary
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The study aims to compare the effects of an education and High Intensity Interval Training program (eHIIT) with the widely used Neuromuscular Exercise and education program (NEMEX-e) on knee OA symptoms and risk factors for cardiovascular disease in people with knee OA and at least one risk factor for developement of cardiovascular disease. The main research questions the study aims to answer are: Is the eHIIT program better than the NEMEX-e program for reducing the risk of cardiovascular disease? Are the two programs equally good at providing improvement in knee symptoms?

Official Title
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Comparative Effectiveness of High-intensity Aerobic Exercise and Biomechanical Neuromuscular Exercise for Treatment of Knee Osteoarthritis: A Randomised Open Label Trial

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Behavioral: eHIIT
* Behavioral: NEMEX-e


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18- years Diagnosis of tibiofemoral knee OA according to the American College of Rheumatology criteria Radiographically confirmed diagnosis of tibiofemoral OA based on radiographs not older than 6 months. Average knee pain level ≥ 4 (0=No pain and 10=Worst pain) over the past week (7 days) At least one of following risk factors for development of cardiovascular disease: Body mass index ≥ 30 kg/m2 Hypertension (or in treatment of): Systolic ≥ 135 and/or diastolic ≥ 85 mm Hg Elevated HbA1c (or in treatment of): ≥ 130.7 mg/dL (44 mmol/mol) Elevated Triglycerides (or in treatment of): ≥ 150 mg/dL (1.7 mmol/L) Elevated Cholesterol (or in treatment of) (Low density lipides, LDL): LDL ≥ 54 mg/dL (3.0 mmol/L) Exclusion Criteria: Contraindication to exercise (e.g., resting systolic blood pressure > 200 or diastolic blood pressure > 115, acute or reoccurring chest pain) Unstable body weight the last 3 months (gain/loss outside +/- 5 kg) Planned weight loss (non-pharmacological, pharmacological, and surgical) during study participation Known current cancer Major cardiovascular event within the last 5 years Insulin dependent type 1 or type 2 diabetes Psoriatic, rheumatoid, or gouty arthritis disease Generalized pain syndromes such as fibromyalgia Lumbar or cervical nerve root compression syndromes Scheduled surgery during study participation Treatment with biological medication Impairments that prevent performance in high intensity aerobic exercise Current or planned participation in other health research intervention studies Pregnant/considering pregnancy Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as a large knee joint effusion, uncontrolled diabetes/hypertension, psychiatric or cognitive disorders, language barriers, or opiate dependency.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Education and High Intensity Interval Training (eHIIT)<br>1 educational session lasting 1 hour. 12 weeks of supervised High Intensity Interval Training (HIIT) 3 times/week. | Behavioral: eHIIT<br>* Education and High intensity Interval Training (Aerobic Exercise) The focus of the one educational session is rationale for aerobic exercise, expected physiological effects of aerobic exercise, diet when performing an exercise program, how the knee accommodates to exercise (including potential experience of muscle soreness and how that is different from joint pain), and management of potential knee OA symptom flares. HIIT is an aerobic exercise form. The eHITT protocol consist of eight 2-minute intervals of high intensity training (with the goal to train at a heart rate of at least 80% of HRmax) followed by 2 minutes of moderate training intensity (with the goal to train at a heart rate of at least 60% of HRmax). There will be several types of exercise modalities for aerobic exercise available (treadmills, cross-trainers, row- and cycle ergometers) and participants may choose whichever they prefer.<br>|
| Active Comparator: Neuromuscular exercise and education program (NEMEX-e)<br>2 educational sessions lasting 1 hour each. 8 weeks of supervised Neuromuscular Exercise 2 times/week. | Behavioral: NEMEX-e<br>* Education and Neuromuscular Exercise The focus of the two educational sessions is on providing knowledge of OA and treatment options to the participants, with a special focus on knee OA, diet, and exercise and its benefits. Furthermore, advice about self-management is given. The exercises are based on neuromuscular principles to improve sensorimotor control and achieve compensatory functional stability. Sensorimotor control is the ability to coordinate muscle activity and maintain functional stability during movement allowing for joint stability during physical activity. Various positions (sitting, lying, standing) are used to achieve the desired postural activity. The overall goal is to obtain muscle control and stability in situations resembling daily life and/or more strenuous activities. The focus is on achieving good quality of the performance in each exercise with appropriate postural orientation (e.g., joint positioned appropriately in relation to each other).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal oxygen consumption (VO2max) | Cardiopulmonary exercise test (CPET) on an ergometer bicycle for evaluation maximal oxygen consumption (VO2max) measured in ml/min/kg | Baseline and Week 12 | 
| Knee pain | The Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale (KOOS-pain), a disease-specific patient-reported instrument designed to assess knee pain in patients with knee osteoarthritis. The KOOS-pain subscale is scored on a 0-100 scale with 100 indicating no pain and 0 indicating extreme pain. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal oxygen consumption (VO2max) | Cardiopulmonary exercise test (CPET) on an ergometer bicycle for evaluation maximal oxygen consumption (VO2max) measured in ml/min/kg | Week 8 and week 26 | 
| Knee pain | The Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale (KOOS-pain), a disease-specific patient-reported instrument designed to assess knee pain in patients with knee osteoarthritis. The KOOS-pain subscale is scored on a 0-100 scale with 100 indicating no pain and 0 indicating extreme pain. | Week 8 and week 26 | 
| Body Mass | Body mass measured in kilograms using a scale | Baseline, Week 12 and Week 26 | 
| Blood Pressure | Systolic and Diastolic blood pressure | Baseline, Week 12 and Week 26 | 
| Triglyceride concentration | From a blood sample | Baseline, Week 12 and Week 26 | 
| Low Density Lipids (LDL) concentration | From a blood sample | Baseline, Week 12 and Week 26 | 
| Cholesterol concentration | From a blood sample | Baseline, Week 12 and Week 26 | 
| Glucose concentration | From a blood sample | Baseline, Week 12 and Week 26 | 
| HbA1c concentration | From a blood sample | Baseline, Week 12 and Week 26 | 
| Patient Global Assessment of disease Impact | Patient-reported degree of patient's perceived impact of their knee OA on their overall life will be obtained using a 100 mm analogue scale (VAS) with anchors: 0= No impact and 100 = Worst imaginable impact. | Baseline, week 8, week 12 and week 26 | 
| Physical Functioning | The Knee injury and Osteoarthritis Outcome Score (KOOS) function subscale (KOOS-function), a disease-specific patient-reported instrument designed to assess physical functioning in patients with knee osteoarthritis. The KOOS-function subscale is scored on a 0-100 scale with 100 indicating no functional impairments and 0 indicating extreme functional impairments. | Baseline, week 8, week 12 and week 26 | 
| Health related quality of Life and physical and mental well-being (Short Form 12 (SF-12)) | The 12-item short form health questionnaire (SF-12) is a measure of physical and mental health. The physical health component is scored between 0-72. The mental health component is scored between 0-70. For both components 0 mean a worse outcome. | Baseline, week 8, week 12 and week 26 |