Exercise and Steroid in Knee Osteoarthritis

Combined Intra Articular Corticosteroid and Physiotherapeutic Exercise in Patients With Osteoarthritis of the Knee: A Random-ised Clinical Trial

Osteoarthritis (OA) of the knee is a very common chronic joint disorder associated pain and disability. As no cure exists, management aims to reduce pain, improve function, and enhance quality of life. The recommended hierarchy of management should consist of exercise in first line, then the add-on of drugs if necessary, and ultimately, if necessary, surgery.

The effect size of exercise therapy is of the same magnitude as most pharmacological treatments but is often without adverse effects. Local pharmacological treatment of the afflicted knee joint is recommended by means of intra-articular injections of corticosteroids, which is considered as a standard medical treatment of knee OA and are included in established guidelines for management of knee OA. While the two treatment approaches have been investigated separately in numerous clinical trials, the efficacy of a combined pharmacological and non-pharmacological approach is not known, despite the high rank of such combined treatment approach on the recommended hierarchy of management.

The purpose of this study is to assess the effects of exercise therapy in combination with intra-articular corticosteroid injections on patient reported pain and function in patients with knee OA.

The hypothesis is that the combined treatment approach (exercise therapy preceded by intra-articular injection of corticosteroid) enhances the clinical outcome compared to exercise therapy preceded by a placebo injection.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Intraarticular steroid; Other: Exercise therapy; Drug: Intraarticular saline

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2000
    • The Parker Institute, Frederiksberg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 40 years or above
• clinical knee osteoarthritis verified by radiography
• pain during level walking of at least 40 mm on a 0-100 mm visual analog scale
• clinical signs of local inflammation
• body mass index between 20 and 35

Exclusion Criteria:

• Exercise therapy within 3 months
• Intraarticular corticosteroid within 3 months
• Counter indications to exercise
• Counter indications to corticosteroid
• pregnant or breast feeding
• Auto immune disease
• Planned surgery in the study period
• significant cardiovascular disease
• significant neuroloigal disease
• significant psychiatric disease
• regional pain syndromes (e.g. fibromyalgia)
• spinal nerve root compression syndromes

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intraarticular steroid + Exercise; Intra-articular corticosteroid treatment with subsequent exercise therapy. Exercise therapy is commenced 2 weeks after injection	Drug: Intraarticular steroid; 1 ml methylprednisolon corticosteroid (40 mg Depo-Medrol®) mixed with 4 ml Lidocain (10 mg/ml) without adrenalin. Injections are done ultrasound guided.; Other: Exercise therapy; The exercise is commenced 2 weeks after injection. The exercise includes a 10 minute warm up phase (ergometer bicycling) followed by strengthening and coordination exercises focusing on trunk, hip and knees. In case of pain or symptom exacerbation, a rescue exercise program is administered, excluding weight bearing activities.
Active Comparator: Intraarticular saline+Exercise; Combined intra-articular saline injection and subsequent exercise therapy. Exercise therapy is commenced 2 weeks after injection	Other: Exercise therapy; The exercise is commenced 2 weeks after injection. The exercise includes a 10 minute warm up phase (ergometer bicycling) followed by strengthening and coordination exercises focusing on trunk, hip and knees. In case of pain or symptom exacerbation, a rescue exercise program is administered, excluding weight bearing activities.; Drug: Intraarticular saline; 1 ml isotonic saline mixed with 4 ml Lidocain (10 mg/ml) without adrenalin. Injections are done ultrasound guided

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee pain	Self-reported pain assessed by the pain subdomain in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire	Change from baseline to week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee pain	Self-reported pain assessed by the pain subdomain in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire	Change from baseline to week 2 and week 26
Knee symptoms	Self-reported knee symptoms, knee related function, quality of life and, function during sports and recreation assessed by the pain subdomain in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire	Change from baseline to week 2, 14, and 26
Functional pain test	Knee OA pain is associated with movement of the afflicted knee. Therefore we assess pain intensity and movement tolerance during repeated squatting. The test has 3 outcomes: 1) The number of pain free squatting movements that can be done in 30 seconds; 2) the number of painful squatting movements that can be done in 30 seconds; and 3) the average pain intensity during the squatting movements assessed on a 0-10 numeric rating scale.	Change from baseline to week 14, and 26
Knee Muscle strength	Assessed by an isokinetic dynamometer	Change from baseline to week 14, and 26
6 minute walk distance	The distance covered during 6 minutes of fast walking	Change from baseline to week 14, and 26
Systemic markers of inflammation in blood	Blood sample	Change from baseline to week 14, and 26
MRI based inflammation	To assess the severity and extent of local inflammation in the knee and surrounding tissues magnetic resonance imaging (MRI) are done before and after intravenous injection of a Gadolinium contrast agent. Contrast agents are only administered to participants with normal kidney function assessed from a standard blood sample	Change from baseline to week 14, and 26

Collaborators and Investigators

• Sponsor: Frederiksberg University Hospital
• Investigators: Study Chair: Marius Henriksen, PhD, Frederiksberg University Hospital

Publications and helpful links

General Publications

• Dall CH, Andersen H, Povlsen TM, Henriksen M. Evaluation of a technology assisted physical activity intervention among hospitalised patients: A randomised study. Eur J Intern Med. 2019 Nov;69:50-56. doi: 10.1016/j.ejim.2019.08.019. Epub 2019 Sep 4.
• Bartholdy C, Klokker L, Bandak E, Bliddal H, Henriksen M. A Standardized "Rescue" Exercise Program for Symptomatic Flare-up of Knee Osteoarthritis: Description and Safety Considerations. J Orthop Sports Phys Ther. 2016 Nov;46(11):942-946. doi: 10.2519/jospt.2016.6908. Epub 2016 Sep 28.
• Henriksen M, Christensen R, Klokker L, Bartholdy C, Bandak E, Ellegaard K, Boesen MP, Riis RG, Bartels EM, Bliddal H. Evaluation of the benefit of corticosteroid injection before exercise therapy in patients with osteoarthritis of the knee: a randomized clinical trial. JAMA Intern Med. 2015 Jun;175(6):923-30. doi: 10.1001/jamainternmed.2015.0461.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: September 16, 2013
• First Submitted That Met QC Criteria: September 16, 2013
• First Posted (Estimate): September 19, 2013

Study Record Updates

• Last Update Posted (Estimate): May 6, 2014
• Last Update Submitted That Met QC Criteria: May 5, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: 101.04; 2012-002607-18 (EudraCT Number)