Saline Injections vs Education and Exercise in Knee Osteoarthritis

NCT ID: NCT03843931

Last Updated: 2020-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

206 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-05

Study Completion Date

2020-12-18

Brief Summary

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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).

Detailed Description

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Conditions

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Osteoarthritis, Knee

Keywords

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Exercise Placebo Injection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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GLA:D

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

Group Type ACTIVE_COMPARATOR

GLA:D

Intervention Type 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.

Intra-articular saline injection

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

Group Type PLACEBO_COMPARATOR

Intra-articular saline injection

Intervention Type 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.

Interventions

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GLA:D

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.

Intervention Type BEHAVIORAL

Intra-articular saline injection

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.

Intervention Type DRUG

Other Intervention Names

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Education and Exercise Physiological salinated water

Eligibility Criteria

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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.
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Marius Henriksen

OTHER

Sponsor Role lead

Responsible Party

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Marius Henriksen

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Marius Henriksen, PhD

Role: STUDY_DIRECTOR

The Parker institute

Henning Bliddal, DMSc

Role: PRINCIPAL_INVESTIGATOR

The Parker institute

Locations

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The Parker Institute, Frederiksberg Hospital

Copenhagen, , Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type DERIVED
PMID: 36657659 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36089229 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34844929 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33407791 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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APPI2-PT-2019-01

Identifier Type: -

Identifier Source: org_study_id