Exercise Therapy for Osteoarthritis Pain: How Does it Work?

NCT04362618 | Unknown

• 1 other identifier: G040919N_KOA_PAIN
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Knee Osteoarthritis

Keywords

Osteoarthritis; Exercise; Acute effects; Inflammation; Endogenous hypoalgesia

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  post-intervention: week 64

Secondary Outcomes (9)

• Different subtypes of pain: pain

  Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)

• Different subtypes of pain: intermittent pain

  Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)

• Different subtypes of pain: constant pain

  Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)

• Different subtypes of pain: central sensitization

  Baseline, during intervention (week 2 and 10), post-intervention (week 13, 26 and 64)

• Function in daily living (KOOS subscale)

  Baseline, post-intervention (week 13, 26 and 64)

Other Outcomes (10)

• Pain catastrophizing (explanatory outcome)

  Assessed at baseline, at week 13, 26 and 64

• Pain hypervigilance (explanatory outcome)

  Assessed at baseline, at week 13, 26 and 64

• Illness perceptions (explanatory outcome)

  Assessed at baseline, at week 13, 26 and 64

Study Arms (3)

Muscle Strengthening Training (MST)-group

EXPERIMENTAL

Subjects allocated to the MST group (n=30) will perform a muscle strengthening training program of 12 weeks.

Other: Muscle Strengthening Training

Behavioral Graded Activity (BGA)-group

EXPERIMENTAL

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.

Behavioral: Behavioral graded activity

Control group

NO INTERVENTION

Subjects allocated to the control group (n=30) have to maintain their current life-style and treatment (if any) and to refrain from other new interventions during 24 weeks.

Interventions

Muscle Strengthening Training OTHER

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.

Muscle Strengthening Training (MST)-group

Behavioral graded activity BEHAVIORAL

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).

Behavioral Graded Activity (BGA)-group

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• pain, nominated by the patient as 3 /10 or higher on a visual analogue scale on most days of the last 3 months
• aged ≥ 50 years.

You may not qualify if:

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

Sponsors & Collaborators

• Vrije Universiteit Brussel: lead
• Universitair Ziekenhuis Brussel: collaborator
• AZ St.-Dimpna Geel: collaborator

Study Sites (1)

Vrije Universiteit Brussel (VUB)

Jette, Brussels Capital, 1090, Belgium

RECRUITING

Related Publications (1)

• Beckwee D, Nijs J, Bierma-Zeinstra SMA, Leemans L, Leysen L, Puts S, Rice D, Schiphof D, Bautmans I. Exercise therapy for knee osteoarthritis pain: how does it work? A study protocol for a randomised controlled trial. BMJ Open. 2024 Jan 10;14(1):e074258. doi: 10.1136/bmjopen-2023-074258.

  PMID: 38199628 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis; Motor Activity; Inflammation

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ivan Bautmans, PhD

  Gerontology department (GERO) and Frailty in Ageing (FRIA) research department, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ivan Bautmans, PhD

CONTACT

+3224774207; ivan.bautmans@vub.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Outcome assessors will be blinded to the maximal extent possible. With regard to this, patients will be asked not to communicate with the assessors about the intervention received. The researcher who is responsible for the acute measurements, is not blinded for group allocation but the researcher responsible for the basal measurements is. Both researchers are blinded for the outcome analyses. Furthermore, at the end of each assessment, the success of assessor blinding will be examined by asking whether the assessor thought the participant had received the experimental or control intervention, including the percentage of certainty. The physiotherapists providing BGA will not be involved in providing MST, and vice versa. Additionally, the physiotherapists will be blinded for outcome measures. The statistician will be blinded to the allocation of the treatment groups and statistical analyses will be performed in a blinded manner.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: 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.

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: April 27, 2020
• Study Start: March 5, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: May 30, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)