Clinical trial NCT03843931: Saline Injections vs Education and Exercise in Knee Osteoarthritis
Official title: A Randomized, Open Label, Parallel Group Study in Patients With Knee Osteoarthritis to Compare Intra-articular Saline Injections With Education Plus Exercise Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: Exercise
Placebo
Injection
Lead sponsor: Frederiksberg University Hospital
Sponsor class: OTHER
First posted: 2019-02-18
Enrollment: 206
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

1. Age ≥50 years.
2. Body Mass index ≤ 35
3. A clinical diagnosis of tibiofemoral OA in the target knee according to the American College of Rheumatology (12).
4. 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).
5. 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:

1. Intra-articular treatments of any kind of either knee 3 months before inclusion
2. Scheduled surgery during study participation
3. Knee joint fluid aspiration within 3 month of baseline visit
4. Participation in exercise therapy within 3 months of baseline visit
5. Evidence of other inflammatory joint disease (e.g. rheumatoid arthritis or gout)
6. History of knee surgery within 12 months
7. History of arthroplasty in the target knee
8. Use of oral glucocorticoids
9. Use of synthetic or non-synthetic opioids
10. Other musculoskeletal, neurological, medical conditions precluding participation in exercise
11. Contraindications to intra-articular injections, such as wounds or skin rash over injection site.
12. Contraindications to exercise
13. Planning to start other treatment for knee OA in the study participation period
14. Regional pain syndromes
15. Generalised pain syndromes such as fibromyalgia
16. Lumbar or cervical nerve root compression syndromes
17. Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or which obstruct participation, such as large knee joint effusion, uncontrolled diabetes, psychiatric disorders, or opiate dependency.

Primary outcomes:
measure: Change from baseline in knee pain
timeFrame: week 9
Secondary outcomes:
measure: Change from baseline in physical function
timeFrame: week 9 and week 12
measure: Change from baseline in symptoms
timeFrame: week 9 and week 12
measure: Change from baseline in knee related quality of life
timeFrame: week 9 and week 12
measure: Change from baseline in patient's global assessment of impact of osteoarthritis
timeFrame: week 9 and week 12
measure: Number of treatment responders according to OMERACT-OARSI response criteria
timeFrame: week 9 and week 12
measure: Change from baseline in 4x10 meter fast walk test
timeFrame: Week 9 and week 12
measure: Change from baseline in the 30 seconds chair stand test
timeFrame: Week 9 and week 12
measure: Change from baseline in Stair climbing test
timeFrame: Week 9 and week 12
Other outcomes:
measure: Joint fluid aspiration volume
timeFrame: week 9 and 12
measure: Change from baseline in swollen knee joint count
timeFrame: week 9 and 12
measure: Change in current knee pain at treatment visits
timeFrame: Week 1, 2, 3, 4, 5, 6, 7, and 8
measure: Time course pattern of changes from baseline in knee OA symptoms during the treatment period
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 7, and 8
measure: Time course pattern of changes from baseline in morning knee OA pain
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9 and 12
measure: Change from baseline in intermittent and constant knee pain
timeFrame: Week 9 and 12
measure: Use of acetaminophen and ibuprofen during study participation
timeFrame: Baseline, Week 9 and 12
Locations:
city: Copenhagen
country: Denmark
facility: The Parker Institute, Frederiksberg Hospital
Study officials:
affiliation: The Parker institute
name: Marius Henriksen, PhD
role: STUDY_DIRECTOR
affiliation: The Parker institute
name: Henning Bliddal, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Henriksen M, Nielsen SM, Christensen R, Kristensen LE, Bliddal H, Bartholdy C, Boesen M, Ellegaard K, Hunter DJ, Altman R, Bandak E. Who are likely to benefit from the Good Life with osteoArthritis in Denmark (GLAD) exercise and education program? An effect modifier analysis of a randomised controlled trial. Osteoarthritis Cartilage. 2023 Jan;31(1):106-114. doi: 10.1016/j.joca.2022.09.001. Epub 2022 Sep 8.
citation: Bandak E, Christensen R, Overgaard A, Kristensen LE, Ellegaard K, Guldberg-Moller J, Bartholdy C, Hunter DJ, Altman R, Bliddal H, Henriksen M. Exercise and education versus saline injections for knee osteoarthritis: a randomised controlled equivalence trial. Ann Rheum Dis. 2022 Apr;81(4):537-543. doi: 10.1136/annrheumdis-2021-221129. Epub 2021 Nov 29.
citation: Bandak E, Overgaard AF, Kristensen LE, Ellegaard K, Guldberg-Moller J, Bartholdy C, Hunter DJ, Altman RD, Christensen R, Bliddal H, Henriksen M. Exercise therapy and patient education versus intra-articular saline injections in the treatment of knee osteoarthritis: an evidence-based protocol for an open-label randomised controlled trial (the DISCO trial). Trials. 2021 Jan 6;22(1):18. doi: 10.1186/s13063-020-04952-5.