Trial Comparing Botulin Toxin Versus Hyaluronic Acid by Intra-articular Injection for the Treatment of Painful Knee Osteoarthritis

Study Overview
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Brief Summary
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In France, osteoarthritis affects about 10 million people and knee osteoarthritis represents 35% of cases. It is thought that more than 2.5 million people older than 65 years have knee osteoarthritis. Currently, osteoarthritis management is based on three major axes: Non-pharmacological means, such as patient education, loss of weight and physical activity General pharmacological treatments: mainly paracetamol and then schedule II and III painkillers as well as nonsteroidal anti-inflammatory agent. Intra-articular pharmacological treatments: Intra-articular injections of corticosteroids: they are recommended during hydarthrotic flare-ups Intra-articular injections of hyaluronic acid (HA) (viscosupplementation) in the absence of intra-articular effusion. However, their efficacy is questioned by most experts in the case of symptomatic knee osteoarthrosis. Sometimes, surgery is the only therapeutic option. However, besides the fact of exposing patients, who are sometimes frail, to several peri- and post-operative complications, the recovery rate (variable according to the prosthesis type and ranging from 5% to 25% at 9 years) in an ageing population justifies waiting as much as possible before surgery. Therefore, it is important to test new therapeutic options for symptomatic osteoarthrosis that will allow postponing the surgical treatment. The use of botulinum toxin (BoNT-A) could thus represents an interesting alternative. BoNT-A is habitually used by intra-muscular injection for its myorelaxant effect in the management of painful reactive periarticular muscle contractures. However, BoNT-A has also antalgic activity independently of the myorelaxant effect. This allows explaining in part the antalgic effect of intra-articular BoNT-A injection. In the literature, six randomized controlled studies (RCS) have compared BoNT-A and intra-articular injections of corticosteroids, hyaluronic acid, or placebo. Only two RCS concerned knee osteoarthritis and compared BoNT-A to corticosteroids and a placebo, respectively, with a significant antalgic effect only in the groups treated with BoNT-A. No study has compared yet the intra-articular injection of BoNT-A to the viscosupplementation by HA in knee osteoarthritis and this is the aim of this trial.

Official Title
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Randomized Controlled Trial Comparing Botulin Toxin Versus Hyaluronic Acid by Intra-articular Injection for the Treatment of Painful Knee Osteoarthritis

Conditions
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Painful Unilateral Femorotibial Knee Osteoarthritis of Any Etiology

Intervention / Treatment
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* Drug: Botulinum toxin A ( BoNT-A)
* Device: Hyaluronic acid (HA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Painful, or predominantly unilateral painful, knee osteoarthritis of any etiology Knee without clinical signs of intra-articular effusion Kellgren score ≥ II on X-ray WOMAC pain sub-score ≥ 5 in the month preceding the inclusion visit Exclusion Criteria: Clinical: Inflammatory arthropathy,infectious, neoplastic within the past year Neuromuscular pathology Cardiorespiratory pathology or any other severe disease that interferes with the functional capacities Any decompensated or unstable chronic pathology Glomerular filtration rate (GFR)<15 mL/min/1.73m²) within the past 6 months HBA1c in diabetic people > 12% within the past 6 months BMI ≥ 35kg/m2 Infection: joint, general, distant, cutaneous Foreign material in the knee to be treated: prosthesis, osteosynthesis material Severe coagulation problem: platelets <100000/mm3 within the past 6 months Allergy to BoNT-A Allergy to HA Pregnant or breast-feeding women Treatment with aminoglycosides or direct oral anticoagulants Treatment with VKA (antihemorrhagic vitamin) if INR (International Normalized Ratio) higher than 3 within the past month Change of anti-pain treatment less than 2 weeks before enrolment Treatment with III pain killers or corticosteroids because of intense pain that does not respond to schedule I and II pain-killers Intra-articular injection of corticosteroids in the previous two months Viscosupplementation and/or injection of BoNT-A in the knee to be treated within the past 6 months Injection of BoNT-A (except the knee to be treated) within the past 3 months Swallowing troubles

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-articular injection of botulinum toxin A<br> | Drug: Botulinum toxin A ( BoNT-A)<br>* Intra-articular injection of BoNT-A<br>|
| Active Comparator: Intra-articular injection of hyaluronic acid<br> | Device: Hyaluronic acid (HA)<br>* Intra-articular injection of Hyaluronic acid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of pain measured using the WOMAC pain sub-score |  | Change from baseline WOMAC pain sub-score at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the antalgic effect of BoNT-A vs hyaluronic acid measured using a verbal rating scale (VRS) |  | 1 week after injection | 
| Evaluation of the patients' functional improvement based on the WOMAC score (stiffness and function sub-score and total score) |  | Before injection, 1 month, 3 months and 6 months following injection | 
| Evaluation of the patients' functional improvement using the Timed Up-and-go Test |  | Before injection, 1 month, 3 months and 6 months following injection | 
| Evaluation of the quality of life based on the SF-36 score |  | Before injection, 1 month, 3 months and 6 months following injection | 
| Frequency, seriousness and severity of adverse event reactions |  | during the 6 months following injection | 
| Changes in pain treatment score (using a correspondence table) |  | Change from baseline pain treatment score at 6 months | 
| Changes in muscular strenght et muscular trophicity (using dynanometer and measure of knee and thin circumference) |  | Before injection, 1 month, 3 months and 6 months following injection | 
| Changes in passive and active articular knee amplitude, by goniometry |  | Before injection, 1 month, 3 months and 6 months following injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee osteoarthritis, Intra-articular botulinum toxin, Hyaluronic acid, Pain, Function