Clinical trial NCT03215602: EXercise as TReatment for osteoArthritis
Official title: EXercise as TReatment for osteoArthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: knee
osteoarthritis
exercise
quadriceps
strength
activities of daily living
treatment outcome
Lead sponsor: Slagelse Hospital
Sponsor class: OTHER
Collaborators: name: The Danish Rheumatism Association
name: Region Zealand
name: Naestved Hospital
name: University of Southern Denmark
First posted: 2017-07-12
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel group, assessor- and patient blinded randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Osteoarthritis (OA) of the knee is a chronic musculoskeletal disease, and a major cause of pain and disability worldwide. Exercise has previously demonstrated good effect in alleviating OA symptoms. However, optimal exercise modes in OA are currently unknown.

This study seeks to evaluate the effects of supplementary focused, knee extensor strength training in addition to neuromuscular exercise (NEMEX) and education in people with OA of the knee as performed in Good Life with osteoArthritis in Denmark (GLA:D ᵀᴹ).

Through a randomized design, study participants will either be allocated to 12 weeks (twice weekly) of NEMEX and education or 12 weeks (twice weekly) of NEMEX and education and focused, knee extensor strength training.

The primary outcome measurement for this study is the Knee injury and Osteoarthritis Outcome Score, subscale Activities of Daily Living (KOOS-ADL), which is a self-reported questionnaire on daily life activities. Other outcomes include parameters of maximal muscle strength and muscle power, muscle imaging, physical function, pain and self-reported health status.

Detailed description: Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases worldwide. In Denmark, it is estimated that approximately 900.000 people, or 1 out of 5 residents are suffering from OA in one or more joints. The annual socio-economic costs (treatment and loss of labour) as a direct consequence of OA in Denmark are estimated to 11.5 billion "Danish kroner" (DKK).

Osteoarthritis of the knee is the most frequently reported and disabling OA subgroup and is mainly reported in middle-aged adults (≥40 years) with an increasing prevalence with increasing age. Knee osteoarthritis is associated with knee pain, loss of lower limb muscle strength, activity limitations and reduced quality of life. Moreover, pain sensitization, i.e. increased responsiveness of nociceptive neurons, is another mechanism involved in pain and disability in knee-OA and may contribute to the frequently reported disparities between pain symptoms and radiographic signs of structural damage.

The current non-surgical treatment recommendations in Denmark as well as internationally include offering one or more of: Patient education, dietary advice, weight loss counselling and exercise. Exercise has proven to be a potent stimulus to improve function, and general quality of life in people with knee-OA. Moreover, exercise has been shown to reduce pain sensitization in knee-OA subjects with clinical signs of sensitization. However, there is still a paucity of information on the exact exercise mode for greatest beneficial effects in the knee-OA population.

Reduced lower limb muscle strength has repeatedly been suggested as one of the main working mechanisms behind knee-OA symptoms and quadriceps muscle strength is even suggested as a potential mediating factor in future knee joint space narrowing and longitudinal worsening of knee-joint pain. A recent systematic review revealed upper leg muscle strength along with joint proprioception to be two of the most potent mediating factors in symptomatic knee-OA.

In a randomized controlled trial (RCT) design, this study seeks to investigate potential added benefits of supplementing NEMEX and education with focused knee extensor strength training in patients with knee-OA. 90 patients deemed ineligible for knee replacement surgery will be recruited from the ambulatory setting at Naestved Hospital. By random allocation, patients will be recruited to either 12 weeks (twice weekly) of NEMEX and education + focused knee extensor strength training (intervention group) or 12 weeks (twice weekly) of NEMEX and education only (control group).

The main outcome is the change in KOOS-ADL from baseline to 12-week follow-up. Other outcomes include the remaining KOOS subscales, self-reported pain, health status, physical activity and patient satisfaction, knee extensor muscle power and knee extensor maximal contractile strength, pain sensitization, MRI assessed thigh muscle quality and physical function.

Eligibility criteria: Inclusion Criteria:

Patients with symptomatic and radiographically confirmed knee-OA who are found not eligible for knee replacement surgery by an orthopaedic surgeon in secondary health care.

Exclusion Criteria:

* Kellgren \& Lawrence score of \<2 on radiography
* Less than "mild" symptoms (mean score \>75 in 0-100 KOOS-ADL)
* Medication: Morphine for pain other than knee-joint pain
* Previous ipsilateral knee arthroplasty
* Rheumatoid arthritis
* Inability to comply with the protocol
* Inadequacy in written and spoken Danish

Primary outcomes:
measure: Knee injury and Osteoarthritis Outcome Score (KOOS) - subscale Activities of daily living (ADL)
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
Secondary outcomes:
measure: Muscle power (watt/kg. bodyweight)
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: Baseline to 6 weeks.
measure: Functional performance (40 m walk & stair-climbs)
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
measure: Pain medication
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
measure: KOOS (remaining four subscales)
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
measure: AE (adverse events) & Serious Adverse Events (SAE)
timeFrame: Primary endpoint: From baseline to 12 weeks.. Secondary endpoint: 12 months.
Other outcomes:
measure: Pain sensitization
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
measure: MRI derived muscle quality assessment
timeFrame: Primary endpoint: Change from baseline to 12 weeks.
measure: Knee extensor isokinetic dynamometry
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
measure: Functional performance (chair rise)
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks..
measure: Visual Analog Scale (VAS)
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
measure: Widespread Pain Index (WPI)
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks & 12 months.
measure: Numeric Rating Scale (NRS)
timeFrame: Continuous assessments from baseline to 12 weeks.
measure: Physical activity level
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary outcomes: 6 weeks & 12 months.
measure: Compliance with exercise
timeFrame: Primary endpoint: 12 weeks..
measure: Surgery and other treatments during follow-up
timeFrame: Primary endpoint: 12 weeks. Secondary endpoints: 6 weeks & 12 months.
measure: EuroQOL 5 domain
timeFrame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
measure: Patient Acceptable Symptom State (PASS)
timeFrame: Primary endpoint: 12 weeks. Secondary endpoint: 6 weeks & 12 months.
measure: Global Perceived Effect (GPE)
timeFrame: Primary endpoint: 12 weeks. Secondary endpoints: 6 weeks & 12 months.
measure: Treatment Failure (TF)
timeFrame: Primary endpoint: 12 weeks. Secondary endpoint: 12 months.
Locations:
city: Naestved
country: Denmark
facility: Department of planned Orthopaedic Surgery, Naestved Hospital
state: Region Zealand
Study officials:
affiliation: University of Southern Denmark and Department of Physiotherapy and Occupational Therapy, Naestved-Slagelse-Ringsted Hospitals.
name: Pætur M Holm, PT, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern Denmark and Naestved-Slagelse-Ringsted Hospitals.
name: Søren T Skou, PT, PhD
role: STUDY_CHAIR
affiliation: Naestved Hospital
name: Henrik M Schøder, MD
role: STUDY_CHAIR
affiliation: Göteborg University
name: Mathias Wernbom, PT, PhD
role: STUDY_CHAIR
References:
citation: Holm PM, Kemnitz J, Bandholm T, Wernbom M, Schroder HM, Skou ST. Muscle Function Tests as Supportive Outcome Measures for Performance-Based and Self-Reported Physical Function in Patients With Knee Osteoarthritis: Exploratory Analysis of Baseline Data From a Randomized Trial. J Strength Cond Res. 2022 Sep 1;36(9):2635-2642. doi: 10.1519/JSC.0000000000003840. Epub 2020 Oct 5.
citation: Holm PM, Nyberg M, Wernbom M, Schroder HM, Skou ST. Intrarater Reliability and Agreement of Recommended Performance-Based Tests and Common Muscle Function Tests in Knee Osteoarthritis. J Geriatr Phys Ther. 2021 Jul-Sep 01;44(3):144-152. doi: 10.1519/JPT.0000000000000266.
citation: Holm PM, Schroder HM, Wernbom M, Skou ST. Low-dose strength training in addition to neuromuscular exercise and education in patients with knee osteoarthritis in secondary care - a randomized controlled trial. Osteoarthritis Cartilage. 2020 Jun;28(6):744-754. doi: 10.1016/j.joca.2020.02.839. Epub 2020 Mar 13.