EXercise as TReatment for osteoArthritis

Knee Osteoarthritis Clinical Trial

— EXTRA  

Official title:

EXercise as TReatment for osteoArthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03215602
• Other study ID #: SJ-517
• Status: Completed
• Phase: N/A
• Start date: July 18, 2017
• Est. completion date: March 31, 2020

Study information

• Verified date: September 2020
• Source: Slagelse Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: March 31, 2020
• Est. primary completion date: March 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Other:
• NEMEX and education + strength training
Optimizing sensorimotor control and achieving functional stability. Increasing knee extensor muscle strength. Teaching everyday disease management.
• NEMEX and education
Optimizing sensorimotor control and achieving functional stability. Teaching everyday disease management.

Locations

Country	Name	City	State
Denmark	Department of planned Orthopaedic Surgery, Naestved Hospital	Naestved	Region Zealand

Sponsors (5)

Lead Sponsor	Collaborator
Slagelse Hospital	Naestved Hospital, Region Zealand, The Danish Rheumatism Association, University of Southern Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pain sensitization	Pan sensitization will be assessed through pain pressure cuff algometry (PPCA). The assessment involves placing a pneumatic pressure cuff with automatic inflation around the participant's lower leg. Through four different tests, the participant is asked to rate pain intensity (VAS). The pain scores along with cuff pressure (kPa) is registered. The PPCA is an increasingly used measure of deep-tissue pain sensitization, which allows for multimodal measurements of pain mechanisms in the knee-OA population.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
Other	MRI derived muscle quality assessment	In order to assess morphologic changes and changes in muscle quality of the knee extensors, patients will undergo two MRI scans (baseline & follow-up). MRI is considered the gold standard in assessing morphometric muscle changes in humans.	Primary endpoint: Change from baseline to 12 weeks.
Other	Knee extensor isokinetic dynamometry	Isokinetic dynamometry will be conducted in order to assess the contractile properties of the knee extensors. The dynamometry assessments will allow for specific strength evaluations and is a validated measure of maximal contractile muscle strength.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
Other	Functional performance (chair rise)	The 30 sec chair-rise (total reps) is part of the recommended functional performance tests in knee OA.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks..
Other	Visual Analog Scale (VAS)	VAS will be derived for the questions: last 24 hours, last week and after 30 min. of walking.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
Other	Widespread Pain Index (WPI)	WPI will be assessed by questions on regional body pain as validated by the American College of Rheumatology.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks & 12 months.
Other	Numeric Rating Scale (NRS)	NRS will be derived before, during and after each exercise session as well as before and after each testing procedure. The NRS assessments will allow for an evaluation of the effects of exercise and functional activities on self-reported pain ratings.	Continuous assessments from baseline to 12 weeks.
Other	Physical activity level	Patient reported physical activity levels.	Primary endpoint: Change from baseline to 12 weeks. Secondary outcomes: 6 weeks & 12 months.
Other	Compliance with exercise	The number of exercise sessions that the patient participates in out of the total 24 supervised sessions.	Primary endpoint: 12 weeks..
Other	Surgery and other treatments during follow-up	Self-reported assessment at baseline, 6 and 12 weeks and at 12 months.	Primary endpoint: 12 weeks. Secondary endpoints: 6 weeks & 12 months.
Other	EuroQOL 5 domain	A self-reported outcome measure of health-related quality of life, covering 5 dimensions (movement, personal care, everyday activities, pain/discomfort and anxiety/depression). Is translated and validated for use in a Danish population.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
Other	Patient Acceptable Symptom State (PASS)	PASS registers how patients perceive their current symptom state. Answered by "yes" or "no" to the question; "When you think of your knee function, will you consider your current condition as satisfying?".	Primary endpoint: 12 weeks. Secondary endpoint: 6 weeks & 12 months.
Other	Global Perceived Effect (GPE)	GPE registers how patients perceive the effects of the interventions on a 7-point likert scale.	Primary endpoint: 12 weeks. Secondary endpoints: 6 weeks & 12 months.
Other	Treatment Failure (TF)	Only answered by patients answering "no" to PASS. TF registers if the patients perceive the intervention as failed. Answered by "yes" or "no" to the question; "Would you consider your current state as being so unsatisfactory that you consider the treatment to have failed?".	Primary endpoint: 12 weeks. Secondary endpoint: 12 months.
Primary	Knee injury and Osteoarthritis Outcome Score (KOOS) - subscale Activities of daily living (ADL)	KOOS is a validated and extensively used self-reported outcome measure for people with knee OA. KOOS consists of five subscales, of which the subscale KOOS-ADL will be the primary outcome for this study. KOOS-ADL consists of 17 questions, which are answered on a 4-point likert scale (0=no problems, 4=extreme problems). KOOS-ADL has demonstrated a test-retest reliability (ICC) of 0.84-0.94 as well as demonstrating responsiveness to change following physical therapy in knee osteoarthritis.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
Secondary	Muscle power (watt/kg. bodyweight)	Knee extensor muscle power (force times acceleration) will be measured using the Nottingham Power Rig (NPR). The NPR measures the power output in total watt and watt pr. bodyweight in kilograms from a seated push on a flat pedal which is transmitted by a lever and chain to spin a flywheel. The NPR is a safe and reliable method to measure explosive knee extensor muscle power and has been validated as a clinically important measure of muscle function in elderly individuals.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: Baseline to 6 weeks.
Secondary	Functional performance (40 m walk & stair-climbs)	Assessment of functional performance involves time (in seconds) taken to complete a 40 m course at fast walking pace as well as time taken to negotiate 9 steps on a standard step-height stair-way. The tests are part of the recommended functional performance tests in knee osteoarthritis.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
Secondary	Pain medication	Assessment of pain medication intake specific for knee pain. Derived as part of self-reported outcome measure.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
Secondary	KOOS (remaining four subscales)	The four remaining subscales of the validated KOOS questionnaire (see primary outcome for further info on KOOS). The 4 remaining subscales cover: symptoms, pain, sport & recreation and quality of life.	Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
Secondary	AE (adverse events) & Serious Adverse Events (SAE)	Continous registration of health issues and injuries. Physiotherapists in charge of the training sessions will monitor potential AE and SAE. Also, during the follow-up visits at week 6 and week 12, the participants will be asked about potential AE's and SAE's using open-probe questions. Finally, the 12 month follow-up will include questions regarding AE's and SAE's during the preceding period from baseline to 12 months.	Primary endpoint: From baseline to 12 weeks.. Secondary endpoint: 12 months.