International guidelines recommend exercise as the first choice treatment for knee osteoarthritis (KOA). Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on KOA pain, but the mechanisms of action are unclear. Understanding these mechanisms is necessary to tailor exercise therapy towards specific mediators and thereby optimize treatment effects. Based on previous studies, both exercise-induced anti-inflammation and endogenous analgesia are promising pathways for pain reduction after exercise therapy. This study aims to examine (anti)-inflammation and endogenous analgesia as mediators for the effect of MST and/or BGA on pain in patients with KOA. Therefore, a 3-arm randomized clinical trial is established: 12 weeks of muscle strengthening training, behavioural graded activity or control. Mediator analysis will be performed. Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists. The results of this research will also find their way into clinical practice: thanks to the current project, tailoring exercise therapy programs towards specific mechanistic factors and thereby optimizing treatment effects will be at the horizon for patients suffering from KOA.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
90
Muscle strengthening training will take place for a period of 12 weeks, in which participants will have 36 exercise sessions (18 at the hospital under supervision of a physiotherapist; 18 unsupervised at home) planned. Muscles of the leg (i.e. quadriceps, hip ab- and adductors) will be trained at 3 set of 10 repetitions at 80% of 1RM with the use of elastic bands. 1RM will be assessed at baseline and the exercise intensity will be progressively increased by 10% of 1RM every two sessions from 50 up to 70-80 % of 1RM. Every 6 sessions, the 1RM will be reassessed and the training resistances will be adapted.
Subjects will receive a behavioural treatment integrated within the concepts of operant conditioning with exercise therapy for a period of 12 weeks, in which the subjects will have maximum 36 BGA sessions (min. 13- max. 18 at the hospital under supervision of a physiotherapist; 18 unsupervised at home) planned. The purpose of BGA is to increase the level of activities in a time-contingent manner and increase the level of physical activity in the subject's daily lives. BGA consists of 3 phases: pain education (phase 1), treatment phase in which subjects increase their level of activity gradually (phase 2) and integration of learned principles in daily live (phase 3).
Vrije Universiteit Brussel (VUB)
Jette, Brussels Capital, Belgium
RECRUITINGKnee pain as primary study outcome
Pain is the primary outcome as it is the primary and most disabling symptom in OA. The pain subscale of the WOMAC Osteoarthritis Index LK3.0 questionnaire will be used for the assessment of pain severity. The Knee injury and Osteoarthritis Outcome Score (KOOS) includes WOMAC Osteoarthritis Index LK3.0 in its complete and original format (with permission). WOMAC (and therefore the pain and symptoms subscale of the KOOS) is a valid tool for subjects with KOA. The KOOS is proven to generate valid and reliable scores.
Time frame: Baseline
Knee pain as primary study outcome
Pain is the primary outcome as it is the primary and most disabling symptom in OA. The pain subscale of the WOMAC Osteoarthritis Index LK3.0 questionnaire will be used for the assessment of pain severity. The Knee injury and Osteoarthritis Outcome Score (KOOS) includes WOMAC Osteoarthritis Index LK3.0 in its complete and original format (with permission). WOMAC (and therefore the pain and symptoms subscale of the KOOS) is a valid tool for subjects with KOA. The KOOS is proven to generate valid and reliable scores.
Time frame: during intervention: week 2 (acute)
Knee pain as primary study outcome
Pain is the primary outcome as it is the primary and most disabling symptom in OA. The pain subscale of the WOMAC Osteoarthritis Index LK3.0 questionnaire will be used for the assessment of pain severity. The Knee injury and Osteoarthritis Outcome Score (KOOS) includes WOMAC Osteoarthritis Index LK3.0 in its complete and original format (with permission). WOMAC (and therefore the pain and symptoms subscale of the KOOS) is a valid tool for subjects with KOA. The KOOS is proven to generate valid and reliable scores.
Time frame: during intervention: week 10 (acute)
Knee pain as primary study outcome
Pain is the primary outcome as it is the primary and most disabling symptom in OA. The pain subscale of the WOMAC Osteoarthritis Index LK3.0 questionnaire will be used for the assessment of pain severity. The Knee injury and Osteoarthritis Outcome Score (KOOS) includes WOMAC Osteoarthritis Index LK3.0 in its complete and original format (with permission). WOMAC (and therefore the pain and symptoms subscale of the KOOS) is a valid tool for subjects with KOA. The KOOS is proven to generate valid and reliable scores.
Time frame: post-intervention: week 13
Knee pain as primary study outcome
Pain is the primary outcome as it is the primary and most disabling symptom in OA. The pain subscale of the WOMAC Osteoarthritis Index LK3.0 questionnaire will be used for the assessment of pain severity. The Knee injury and Osteoarthritis Outcome Score (KOOS) includes WOMAC Osteoarthritis Index LK3.0 in its complete and original format (with permission). WOMAC (and therefore the pain and symptoms subscale of the KOOS) is a valid tool for subjects with KOA. The KOOS is proven to generate valid and reliable scores.
Time frame: post-intervention: week 26
Knee pain as primary study outcome
Pain is the primary outcome as it is the primary and most disabling symptom in OA. The pain subscale of the WOMAC Osteoarthritis Index LK3.0 questionnaire will be used for the assessment of pain severity. The Knee injury and Osteoarthritis Outcome Score (KOOS) includes WOMAC Osteoarthritis Index LK3.0 in its complete and original format (with permission). WOMAC (and therefore the pain and symptoms subscale of the KOOS) is a valid tool for subjects with KOA. The KOOS is proven to generate valid and reliable scores.
Time frame: post-intervention: week 64
Different subtypes of pain: pain
Pain will be measured using the Visual analogue scale (VAS).
Time frame: Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)
Different subtypes of pain: intermittent pain
Intermittent pain will be measured using a short and easily applicable self-reported measure, i.e. intermittent and constant pain (ICOAP).
Time frame: Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)
Different subtypes of pain: constant pain
Constant pain, will be measured using a short and easily applicable self-reported measure, i.e. Intermittent and constant pain (ICOAP).
Time frame: Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)
Different subtypes of pain: central sensitization
Central sensitization will be measured using an easily applicable self-reported measure i.e. Central Sensitization Inventory (CSI).
Time frame: Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)
Function in daily living (KOOS subscale)
Function in daily living will be measured using self-reported measures. The KOOS function in daily living (ADL) subscale and functioning in sports and recreation subscale are reliable and valid scales to measure function in people with osteoarthritis. The patient global assessment (PGA) is a recommended questionnaire in clinical trials of rehabilitation interventions for OA and it measures the improvement or deterioration of their condition.
Time frame: Baseline, post-intervention (week 13, 26 and 64)
Function in daily living (PGA)
Function in daily living will be measured using self-reported measures. The patient global assessment (PGA) is a recommended questionnaire in clinical trials of rehabilitation interventions for OA and it measures the improvement or deterioration of their condition.
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Time frame: Assessed at baseline and post-intervention (at week 13, 26 and 64)
Treatment adherence
Patient adherence for the treatment sessions will be calculated as the ratio of the number of treatment sessions that were actually carried out versus the number of prescribed sessions. Compliance will be calculated as the ratio of the total training duration (recorded in the logbooks) versus the prescribed total training duration, multiplied by 100.
Time frame: During the intervention (week 1-12) and at week 13
Treatment compliance
Compliance will be calculated as the ratio of the total training duration (recorded in the logbooks) versus the prescribed total training duration, multiplied by 100.
Time frame: During the intervention (week 1-12) and at week 13
Health care cost effectiveness
Medical consumption, the type, dose, method of administration and frequency of analgesic, NSAID or symptom-modifying medication, as well as surgeries (total or partial knee replacements) will be recorded. Health care use will be evaluated using the combination of three questionnaires: (1) the Medical Consumption Questionnaire (2) the Productivity Cost Questionnaire and (3) the EuroQol EQ-5D.
Time frame: Assessed at baseline, at week 13, 26 and 64