EXercise as TReatment for osteoArthritis (EXTRA)

September 1, 2020 updated by: Pætur Mikal Holm, Slagelse Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Region Zealand
      • Naestved, Region Zealand, Denmark, 4700
        • Department of planned Orthopaedic Surgery, Naestved Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: NEMEX and education + strength training

Participants will undergo 12 weeks of twice weekly exercise. Each exercise session will last for 70-90 min. and will consist of 1 hour of specific exercises to optimize sensorimotor control and achieve compensatory functional stability performed in a multiple-joint weight-bearing specific manner. The final part of the session will consist of focused knee extensor strength training performed in gym machines (knee extension & leg-press) in a combination of low-load fatiguing exercises (knee-extension) followed by high-load exercises (leg-press).

Additionally, participants will receive 2 educational sessions, which include disease- and exercise specific counseling.
Other: NEMEX and education + strength training
Optimizing sensorimotor control and achieving functional stability. Increasing knee extensor muscle strength. Teaching everyday disease management.
Other Names:
  • GLA:D + strength training
Active Comparator: NEMEX and education

Participants will undergo 12 weeks of twice weekly exercise. Each exercise session will last for approximately 60 min. and will consist of 1 hour of specific exercises to optimize sensorimotor control and achieve compensatory functional stability performed in a multiple-joint weight-bearing specific manner.

Additionally, participants will receive 2 educational sessions, which include disease- and exercise specific counseling.
Other: NEMEX and education
Optimizing sensorimotor control and achieving functional stability. Teaching everyday disease management.
Other Names:
  • GLA:D

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Knee injury and Osteoarthritis Outcome Score (KOOS) - subscale Activities of daily living (ADL)
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle power (watt/kg. bodyweight)
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: Baseline to 6 weeks.
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.
Functional performance (40 m walk & stair-climbs)
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
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.
Pain medication
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
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.
KOOS (remaining four subscales)
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
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.
AE (adverse events) & Serious Adverse Events (SAE)
Time Frame: Primary endpoint: From baseline to 12 weeks.. Secondary endpoint: 12 months.
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.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain sensitization
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
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.
MRI derived muscle quality assessment
Time Frame: Primary endpoint: Change from baseline to 12 weeks.
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.
Knee extensor isokinetic dynamometry
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
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.
Functional performance (chair rise)
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks..
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..
Visual Analog Scale (VAS)
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks.
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.
Widespread Pain Index (WPI)
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoint: 6 weeks & 12 months.
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.
Numeric Rating Scale (NRS)
Time Frame: Continuous assessments from baseline to 12 weeks.
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.
Physical activity level
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary outcomes: 6 weeks & 12 months.
Patient reported physical activity levels.
Primary endpoint: Change from baseline to 12 weeks. Secondary outcomes: 6 weeks & 12 months.
Compliance with exercise
Time Frame: Primary endpoint: 12 weeks..
The number of exercise sessions that the patient participates in out of the total 24 supervised sessions.
Primary endpoint: 12 weeks..
Surgery and other treatments during follow-up
Time Frame: Primary endpoint: 12 weeks. Secondary endpoints: 6 weeks & 12 months.
Self-reported assessment at baseline, 6 and 12 weeks and at 12 months.
Primary endpoint: 12 weeks. Secondary endpoints: 6 weeks & 12 months.
EuroQOL 5 domain
Time Frame: Primary endpoint: Change from baseline to 12 weeks. Secondary endpoints: 6 weeks & 12 months.
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.
Patient Acceptable Symptom State (PASS)
Time Frame: Primary endpoint: 12 weeks. Secondary endpoint: 6 weeks & 12 months.
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.
Global Perceived Effect (GPE)
Time Frame: Primary endpoint: 12 weeks. Secondary endpoints: 6 weeks & 12 months.
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.
Treatment Failure (TF)
Time Frame: Primary endpoint: 12 weeks. Secondary endpoint: 12 months.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Slagelse Hospital

Collaborators

University of Southern Denmark
Naestved Hospital
The Danish Rheumatism Association
Region Zealand

Investigators

  • Principal Investigator: Pætur M Holm, PT, MSc, University of Southern Denmark and Department of Physiotherapy and Occupational Therapy, Naestved-Slagelse-Ringsted Hospitals.
  • Study Chair: Søren T Skou, PT, PhD, University of Southern Denmark and Naestved-Slagelse-Ringsted Hospitals.
  • Study Chair: Henrik M Schøder, MD, Naestved Hospital
  • Study Chair: Mathias Wernbom, PT, PhD, Göteborg University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 18, 2017

Primary Completion (Actual)

March 8, 2019

Study Completion (Actual)

March 31, 2020

Study Registration Dates

First Submitted

July 10, 2017

First Submitted That Met QC Criteria

July 11, 2017

First Posted (Actual)

July 12, 2017

Study Record Updates

Last Update Posted (Actual)

September 2, 2020

Last Update Submitted That Met QC Criteria

September 1, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SJ-517

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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