Exercise Therapy for Osteoarthritis Pain: How Does it Work?

Not Applicable

Recruiting

• Conditions: Knee Osteoarthritis
• Interventions: Other: Muscle Strengthening Training; Behavioral: Behavioral graded activity

• Registration Number: NCT04362618
• Lead Sponsor: Vrije Universiteit Brussel

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-28
• Study Start: 2020-03-05
• Study First Submitted QC: 2020-04-22
• Study First Posted: 2020-04-27
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-26
• Last Update Posted: 2023-05-30
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. KOA according to the clinical American College of Rheumatology (ACR) criteria. The clinical ACR criteria for KOA are: knee pain and at least 3 of the 6 following features: age ≥50, morning stiffness <30 minutes, crepitus, bony tenderness, bony enlargement, no palpable warmth. KOA will be confirmed with radiographs, including anterior-posterior (AP) and medio-lateral (ML) radiographs for imaging the tibiofemoral joint, and an axial view for imaging the patellofemoral joint. Kellgren and Lawrence (K&L) grading system for OA will be applied, with K&L grade 2 or higher defined as OA; radiographic KOA is defined as definite osteophytes and possible joint space narrowing.
2. pain, nominated by the patient as 3 /10 or higher on a visual analogue scale on most days of the last 3 months
3. aged ≥ 50 years.

Exclusion Criteria

1. treatment with exercise therapy or joint infiltrations (e.g., corticosteroids, hyaluronic acid) in the preceding 6 months;
2. being on a waiting list for knee replacement;
3. any contra-indication for exercise therapy as established by the treating physician;
4. corticosteroid infiltrations in the last 6 months;
5. cognitive impairment (unable to understand the test instructions and/or Mini Mental State Examination score <23/30);
6. unable to understand the Dutch language;
7. inflammation unrelated to OA (e.g. due to acute or chronic infection) established by CRP>10mg/L.
8. presence of a disorder and/or medication that influences pain and/or the immune system

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Muscle Strengthening Training (MST)-group	Muscle Strengthening Training	Subjects allocated to the MST group (n=30) will perform a muscle strengthening training program of 12 weeks.
Behavioral Graded Activity (BGA)-group	Behavioral graded activity	Subjects allocated to the BGA group (n=30) will perform a rehabilitation program according to the principles of behavioural graded activity for a period of 12 weeks.

Primary Outcome Measures

Name	Time	Method
Knee pain as primary study outcome	post-intervention: week 64	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.

Secondary Outcome Measures

Name	Time	Method
Different subtypes of pain: pain	Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)	Pain will be measured using the Visual analogue scale (VAS).
Treatment compliance	During the intervention (week 1-12) and at week 13	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.
Function in daily living (KOOS subscale)	Baseline, post-intervention (week 13, 26 and 64)	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.
Health care cost effectiveness	Assessed at baseline, at week 13, 26 and 64	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.
Different subtypes of pain: constant pain	Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)	Constant pain, will be measured using a short and easily applicable self-reported measure, i.e. Intermittent and constant pain (ICOAP).
Function in daily living (PGA)	Assessed at baseline and post-intervention (at week 13, 26 and 64)	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.
Different subtypes of pain: intermittent pain	Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)	Intermittent pain will be measured using a short and easily applicable self-reported measure, i.e. intermittent and constant pain (ICOAP).
Different subtypes of pain: central sensitization	Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)	Central sensitization will be measured using an easily applicable self-reported measure i.e. Central Sensitization Inventory (CSI).
Treatment adherence	During the intervention (week 1-12) and at week 13	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.

Trial Locations

Locations (1)

Vrije Universiteit Brussel (VUB); 🇧🇪 Jette, Brussels Capital Region, Belgium