Intra Articular Injection of Botulinum Toxin Versus Corticoids in Gonarthrosis

Study Overview
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Brief Summary
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We believe we can demonstrate a link between the analgesic action of intra-articular injection of botulinum toxin and synovial inflammation by Dynamic Contrast Enhancement (DCE) perfusion Magnetic Resonance Imaging (MRI).

Detailed Description
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Knee osteoarthritis is one of the most common causes of joint pain and functional disability in the general population. Intra-articular infiltrations of corticoids are indicated for painful crisis especially if accompanied of effusion. However, this effect lasts only 2 weeks. Given the lack of effective long-term medical-infiltrative treatment, we believe that botulinum toxin type A could be used by its direct action on mediators of neuro-gene inflammation at the joint level and its indirect medullary action by retrograde migration. To date, 2 published randomized controlled trials and one unpublished Phase Ib clinical trial have shown that botulinum toxin injected intraarticularly improves pain and functionality in gonarthrosis. Dynamic Contrast Enhancement (DCE) Magnetic Resonance Imaging (MRI) demonstrated the correlation between synovial inflammation and pain in gonarthrosis in a cohort of 454 subjects. It has also made it possible, via the monitoring of synovial inflammation, to demonstrate the efficacy of treatments in patients suffering from rheumatoid arthritis in the early phase, juvenile chronic arthritis or osteoarthritis. DCE MRI perfusion therefore appears here as the technique of choice to follow the evolution of synovial inflammation after botulinum toxin injection in patients with symptomatic gonarthrosis.

Official Title
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Analysis of Antalgic Efficacy of an Intra Articular Injection of Botulinum Toxin Versus Corticoids in Gonarthrosis by Perfusion MRI:a Superiority, Randomized, Controlled, Double Blind Study

Conditions
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Joint Diseases, Knee, Therapeutics, Magnetic Resonance Imaging

Intervention / Treatment
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* Drug: Botulinum Toxin Type A 100U
* Drug: Botulinum Toxin Type A 200U
* Drug: Triamcinolone Hexacetonide Inj Susp 20 MG/ML


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presenting gonarthrosis of degenerative origin, Kellgren/Lawrence Radiological Stage I to III, with a maturity of more than 18 months With pain intensity greater than or equal to 50/100 on an VAS In case of bilateral gonarthrosis, the VAS of the contralateral knee must be less than or equal to 30/100 Presenting a failure of conventional per os treatments (non-steroidal anti-inflammatory drugs, analgesics) Affiliated with a social security scheme For women of childbearing age: effective contraception for the duration of the study Exclusion Criteria: Patient presenting at the time of the inclusion visit: an inflammatory attack, septic or inflammatory arthritis, a generalized infectious episode in progress Local or regional local skin lesion Need of an arthroplasty within the next 12 months Having received corticosteroids or other molecules in intra-articular infiltration in the last 6 months History of traumatic knee injury (bone injury in the past 24 months), bone, ligament or meniscal surgery in the past 24 months History of disabling peripheral nerve injury Severe bleeding disorders, anticoagulant treatment in progress or double antiplatelet aggregation BMI > 35 kg/m2 Coxarthrosis with projected knee pain Pregnant or breastfeeding woman Patient under guardianship and protection of justice Allergy/contraindication to botulinum toxin type A, corticoids Usual contraindication to MRI Allergy to the contrast product

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botulinum Toxin Type A 100U<br>one intra-articular injection in the painful knee 30 days after the inclusion visit | Drug: Botulinum Toxin Type A 100U<br>* one intra-articular injection of 100 U of botulinum toxin type A, diluted in 2 ml of 0.9% SSI<br>* Other names: Botox 100 UNT Injection;|
| Experimental: Botulinum Toxin Type A 200U<br>one intra-articular injection in the painful knee 30 days after the inclusion visit | Drug: Botulinum Toxin Type A 200U<br>* one intra-articular injection of 200 U of botulinum toxin type A, diluted in 4 ml of 0.9% SSI<br>* Other names: Botox 200 UNT Injection;|
| Active Comparator: Triamcinolone Hexacetonide 20 MG/ML<br>one intra-articular injection in the painful knee 30 days after the inclusion visit | Drug: Triamcinolone Hexacetonide Inj Susp 20 MG/ML<br>* one intra-articular injection of 2 ml Triamcinolone Hexacetonide<br>* Other names: HEXATRIONE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assesment of vascularization by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) according to the % Area Under the Curve (AUC) of perfusion value |  | one month post-injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain analysis by the visual analogue scale (VAS) | Evolution kinetics of daily pain collected during the first 3 months post-injection allowing to deduce the onset and duration of analgesic efficacy in number of days. The pain VAS is a continuous scale comprised of a horizontal line, usually 10 centimeters (100 mm) in length, anchored by 2 verbal descriptors, one for each symptom extreme: no pain (score of 0) and pain as bad as it could be (score of 100 [100-mm scale]) | during the first 3 months after injection | 
| Joint amplitude measured by goniometry | To measure range of motion of the knee | at 1, 3, 6 month post-injection | 
| Western Ontario McMaster University Osteoarthritis (WOMAC) Index | An arthritic pain scoring system ranging from 0-no pain/disability to 100-most severe pain/disability | at 1, 3, 6 month post-injection | 
| Two minutes walk | This test measure the distance walked in two minutes | at 1, 3, 6 month post-injection | 
| Frequency of consumption of analgesics |  | at 1, 3, 6 month post-injection | 
| Amount of consumption of analgesics |  | at 1, 3, 6 month post-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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knee, Arthrosis, Botulinum toxin, Magnetic Resonance Imaging