A Randomized, Open Label, Parallel Group Study in Patients With Knee Osteoarthritis to Compare Intra-articular Saline Injections With Education Plus Exercise Therapy
Overview
- Phase
- Phase 2
- Intervention
- Intra-articular saline injection
- Conditions
- Osteoarthritis, Knee
- Sponsor
- Marius Henriksen
- Enrollment
- 206
- Locations
- 1
- Primary Endpoint
- Change from baseline in knee pain
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition mainly affecting older people, causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended by leading international organisations and authorities based on extensive research that documents that exercise and education are superior to no-attention control groups.
In Denmark, an initiative to implement these recommendations was initiated in 2013. The initiative is called Good Life with osteoArthritis in Denmark (GLA:D) and aims at facilitating high quality care of patients with OA in the Danish population. The core components of the GLA:D program are 8 weeks of education (2 sessions) and supervised neuromuscular exercise delivered by GLA:D certified physiotherapists. The GLA:D concept has been exported to Canada, China and Australia.
While several randomised controlled trials have investigated exercise and education for knee OA none have used a placebo comparison group. The effect size of exercise plus education therapy is in line with the current theories that the contact with a caring clinician that believes in efficacy of the treatments he/she provides can result in beneficial health effects. In exercise and education programs (such as the GLA:D program) frequent and lengthy contacts with a physiotherapist are typically necessary. Hence, a significant proportion of the beneficial effects can be expected to be attributable to placebo or placebo.like effects.
In trials of intra-articular treatment of knee OA (e.g. in trials of corticosteroids, viscosupplementation, or platelet-rich-plasma) saline injections are a commonly used as placebo comparator. While saline is recognised as a pharmacologically inert agent, a recent systematic review and meta-analysis concluded that although intra-articular saline injection is often used as a "placebo" treatment in clinical trials for knee OA it can provide substantial pain relief. The effect size of saline injections is in line with the current theories that the "invasiveness" of a procedure is an important determinant for the magnitude of placebo effects.
This trial aims to compare a widely used 8-week education plus exercise program (the GLA:D program) with 4 intra-articular saline injections as treatments of knee OA symptoms. Outcomes are taken at baseline, after 8-weeks of treatment (week 9) and after additionally 4 weeks of follow-up (week 12).
Investigators
Marius Henriksen
Professor
Frederiksberg University Hospital
Eligibility Criteria
Inclusion Criteria
- •Age ≥50 years.
- •Body Mass index ≤ 35
- •A clinical diagnosis of tibiofemoral OA in the target knee according to the American College of Rheumatology (12).
- •Average knee pain in the last week during weight bearing activities of at least 4 on a 0 to 10 points scale (0=no pain; 10=worst possible pain).
- •Verification of clinical diagnosis by definite tibiofemoral OA on posterior-anterior weight bearing semi-flexed knee radiographs with severity equivalent to Kellgren and Lawrence grade 2 or more.
Exclusion Criteria
- •Intra-articular treatments of any kind of either knee 3 months before inclusion
- •Scheduled surgery during study participation
- •Knee joint fluid aspiration within 3 month of baseline visit
- •Participation in exercise therapy within 3 months of baseline visit
- •Evidence of other inflammatory joint disease (e.g. rheumatoid arthritis or gout)
- •History of knee surgery within 12 months
- •History of arthroplasty in the target knee
- •Use of oral glucocorticoids
- •Use of synthetic or non-synthetic opioids
- •Other musculoskeletal, neurological, medical conditions precluding participation in exercise
Arms & Interventions
Intra-articular saline injection
Intra-articular saline injection (5 ml of 0.9% sodium chloride) every 2 weeks over an 8-week period
Intervention: Intra-articular saline injection
Outcomes
Primary Outcomes
Change from baseline in knee pain
Time Frame: week 9
Assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale (patient-reported questionnaire). The KOOS pain subscale consists of 9 questions with a five-point Likert scale scoring system (ranging from 0 (least severe) to 4 (most severe)). The answers are summed and a 0-100 normalized score is calculated with 0 indicating extreme pain and 100 indicating no pain.
Secondary Outcomes
- Change from baseline in physical function(week 9 and week 12)
- Change from baseline in symptoms(week 9 and week 12)
- Change from baseline in knee related quality of life(week 9 and week 12)
- Change from baseline in patient's global assessment of impact of osteoarthritis(week 9 and week 12)
- Number of treatment responders according to OMERACT-OARSI response criteria(week 9 and week 12)
- Change from baseline in 4x10 meter fast walk test(Week 9 and week 12)
- Change from baseline in the 30 seconds chair stand test(Week 9 and week 12)
- Change from baseline in Stair climbing test(Week 9 and week 12)