Saline Injections vs Education and Exercise in Knee Osteoarthritis

NCT03843931 | Completed Phase 2 DMC

• 1 other identifier: APPI2-PT-2019-01
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 1

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).

Conditions

Osteoarthritis, Knee

Keywords

Exercise; Placebo; Injection

Outcome Measures

Primary Outcomes (1)

• Change from baseline in knee pain

  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.

  week 9

Secondary Outcomes (8)

• 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

Other Outcomes (7)

• Joint fluid aspiration volume

  week 9 and 12

• Change from baseline in swollen knee joint count

  week 9 and 12

• Change in current knee pain at treatment visits

  Week 1, 2, 3, 4, 5, 6, 7, and 8

Study Arms (2)

GLA:D

ACTIVE COMPARATOR

8 weeks of education (1 session/week for 2 weeks) and exercise therapy (2 sessions/week for 6 week)

Behavioral: GLA:D

Intra-articular saline injection

PLACEBO COMPARATOR

Intra-articular saline injection (5 ml of 0.9% sodium chloride) every 2 weeks over an 8-week period

Drug: Intra-articular saline injection

Interventions

GLA:D BEHAVIORAL

The GLA:D exercise and education program is an 8-week treatment program delivered by GLA:D certified physiotherapists. It consists of 2 educational sessions over 2 weeks (1/week in week 1 and 2) and 12 exercise sessions over 6 weeks (2/week in weeks 2 thru 8) The 2 educational sessions provide knowledge of OA, treatment and self-management, with a special focus on exercise and its benefits. The exercise part lasts for 6 weeks with 2 exercise sessions per week of approximately 1 hour (12 sessions total). The exercise sessions are group based at a facility supervised by a GLA:D certified physiotherapist. The goal is the obtain muscle control and stability in situations resembling daily life and/or more strenuous activities.

Also known as: Education and Exercise

GLA:D

Intra-articular saline injection DRUG

Four \[4\] dosages of 5 ml intra-articular isotonic saline (0.9% (9 mg/mL) Sodium Chloride Injection (sterile, isotonic solution of sodium chloride and sterile water for injection)) every other week from baseline (week 1, 3, 5 and 7 = 4 injections). The injections will be carried out with a 21 gauge (38 mm) needle and a Luer-lock syringe under ultrasound guidance to ensure that the needle is inserted into the study knee joint cavity and document correct deposition of the bolus in the joint cavity. If the investigator detects presence of excessive joint fluid during the ultrasound guided preparation of the injection, this will be aspirated before injection of the saline - if possible.

Also known as: Physiological salinated water

Intra-articular saline injection

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Contraindications to intra-articular injections, such as wounds or skin rash over injection site.
• Contraindications to exercise
• Planning to start other treatment for knee OA in the study participation period
• Regional pain syndromes
• Generalised pain syndromes such as fibromyalgia
• Lumbar or cervical nerve root compression syndromes

Sponsors & Collaborators

• Marius Henriksen: lead

Study Sites (1)

The Parker Institute, Frederiksberg Hospital

Copenhagen, 2000, Denmark

Location

Related Publications (4)

• Henriksen M, Christensen R, Kristensen LE, Bliddal H, Bartholdy C, Boesen M, Ellegaard K, Guldberg-Moller J, Hunter DJ, Altman R, Bandak E. Exercise and education vs intra-articular saline for knee osteoarthritis: a 1-year follow-up of a randomized trial. Osteoarthritis Cartilage. 2023 May;31(5):627-635. doi: 10.1016/j.joca.2022.12.011. Epub 2023 Jan 16.

  PMID: 36657659 DERIVED

• 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.

  PMID: 36089229 DERIVED

• 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.

  PMID: 34844929 DERIVED

• 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.

  PMID: 33407791 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Motor Activity

Interventions

Educational Status; Exercise; Sodium Chloride

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Socioeconomic Factors; Population Characteristics; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Marius Henriksen, PhD

  The Parker institute

  STUDY DIRECTOR

• Henning Bliddal, DMSc

  The Parker institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 13, 2019
• First Posted: February 18, 2019
• Study Start: August 5, 2019
• Primary Completion: December 2, 2020
• Study Completion: December 18, 2020
• Last Updated: December 22, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)