Clinical trial NCT04362618: Exercise Therapy for Osteoarthritis Pain: How Does it Work?
Official title: Exercise Therapy for Osteoarthritis Pain: How Does it Work?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: Osteoarthritis
Exercise
Acute effects
Inflammation
Endogenous hypoalgesia
Lead sponsor: Vrije Universiteit Brussel
Sponsor class: OTHER
Collaborators: name: Universitair Ziekenhuis Brussel
name: AZ St.-Dimpna Geel
First posted: 2020-04-27
Enrollment: 90
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The patients will be randomly allocated to 12 weeks of either muscle strengthening training (MST), behavioural graded activity (BGA) or control. Randomization will be performed by using the method of randomly permuted blocks, utilising a computer-generated random number sequence. To keep both intervention groups balanced, randomization will be stratified for sex (male versus female) baseline inflammation status (hsCRP\<3mg/L versus hsCRP ≥3mg/L) and baseline central sensitization status (central sensitization inventory (CSI) score \<40 versus CSI score ≥ 40).

A list with patient numbers and the group allocation that results from this randomization procedure will be securely stored and only an independent researcher will have direct access to the randomization list. Patients will be scheduled to receive their first assessment within 1 week of randomisation.

Patients will be recruited in primary care and participating hospitals. Announcements will be placed in newspapers, pharmacies etc.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Knee pain as primary study outcome
timeFrame: Baseline
measure: Knee pain as primary study outcome
timeFrame: during intervention: week 2 (acute)
measure: Knee pain as primary study outcome
timeFrame: during intervention: week 10 (acute)
measure: Knee pain as primary study outcome
timeFrame: post-intervention: week 13
measure: Knee pain as primary study outcome
timeFrame: post-intervention: week 26
measure: Knee pain as primary study outcome
timeFrame: post-intervention: week 64
Secondary outcomes:
measure: Different subtypes of pain: pain
timeFrame: Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)
measure: Different subtypes of pain: intermittent pain
timeFrame: Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)
measure: Different subtypes of pain: constant pain
timeFrame: Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)
measure: Different subtypes of pain: central sensitization
timeFrame: Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)
measure: Function in daily living (KOOS subscale)
timeFrame: Baseline, post-intervention (week 13, 26 and 64)
measure: Function in daily living (PGA)
timeFrame: Assessed at baseline and post-intervention (at week 13, 26 and 64)
measure: Treatment adherence
timeFrame: During the intervention (week 1-12) and at week 13
measure: Treatment compliance
timeFrame: During the intervention (week 1-12) and at week 13
measure: Health care cost effectiveness
timeFrame: Assessed at baseline, at week 13, 26 and 64
Other outcomes:
measure: Pain catastrophizing (explanatory outcome)
timeFrame: Assessed at baseline, at week 13, 26 and 64
measure: Pain hypervigilance (explanatory outcome)
timeFrame: Assessed at baseline, at week 13, 26 and 64
measure: Illness perceptions (explanatory outcome)
timeFrame: Assessed at baseline, at week 13, 26 and 64
measure: Dietary intake (explanatory outcome)
timeFrame: Assessed at baseline, at week 13, 26 and 64
measure: Inflammation (as treatment mediator)
timeFrame: Assessments will be performed at baseline, during intervention (at week 2 or week 3 and at week 10 or week 11; pre- and post-treatment for the acute effects), at week 13 (at least 48 hours after the last intervention) and at week 64
measure: Endogenous analgesia as treatment mediator: electrical detection threshold
timeFrame: Assessments will be performed at baseline, during intervention (at week 2 or week 3 and at week 10 or week 11; pre- and post-treatment for the acute effects), and at week 13 (at least 48 hours after the last intervention) and week 64
measure: Endogenous analgesia as treatment mediator: electrical pain threshold
timeFrame: Assessments will be performed at baseline, during intervention (at week 2 or week 3 and at week 10 or week 11; pre- and post-treatment for the acute effects), and at week 13 (at least 48 hours after the last intervention) and at week 64
measure: Endogenous analgesia as treatment mediator: temporal summation
timeFrame: Assessments will be performed at baseline, during intervention (at week 2 or week 3 and at week 10 or week 11; pre- and post-treatment for the acute effects), at week 13 (at least 48 hours after the last intervention) and at week 64
measure: Endogenous analgesia as treatment mediator: conditioned pain modulation
timeFrame: Assessments will be performed at baseline, and at week 13 (at least 48 hours after the last intervention) and at week 64.
measure: Endogenous analgesia as treatment mediator: offset-analgesia
timeFrame: Assessments will be performed at baseline and at week 13 (at least 48 hours after the last intervention) and at week 64.
Locations:
city: Jette
country: Belgium
facility: Vrije Universiteit Brussel (VUB)
state: Brussels Capital Region
Study officials:
affiliation: Gerontology department (GERO) and Frailty in Ageing (FRIA) research department, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium
name: Ivan Bautmans, PhD
role: PRINCIPAL_INVESTIGATOR
References: