Efficacy of an Intra-articular Injection of Botulinum Toxin A Associated With Splinting for Base-of-thumb Osteoarthritis

Study Overview
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Brief Summary
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The primary purpose of this study is to determine whether a single ultrasound-guided intra-articular injection of botulinum toxin A associated to splinting is effective in reducing pain at 3 months in base-of-thumb osteoarthritis.

Detailed Description
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Base-of-thumb osteoarthritis is a common condition affecting middle-age persons. Base-of-thumb osteoarthritis induces pain and hand-specific limitations in activities. For short and midterm effects, therapeutic options usually include splinting, exercise therapy and intra-articular injections of glucocorticoids or hyaluronic acid. However, evidence of efficacy of intra-articular therapies in base-of-thumb osteoarthritis and international guidelines are inconsistent. Recently, the use of intra-articular botulinum toxin A as a pain killer has raised intense interest. The exact mechanisms of pain modulation by botulinum toxin A in osteoarthritis are unclear. It has been suggested that botulinum toxin A could directly reduce peripheral sensitization and indirectly reduce central sensitization. Indeed, recent studies suggest an inhibitory role of botulinum toxin A on the release of mediators involved in nociception, such as P substance, calcitonin gene-related peptide and glutamate. Open and randomized controlled trials of botulinum toxin A in knee osteoarthritis support short to mid-term positive clinical effects on pain. However, no study has reported results for base-of-thumb osteoarthritis

Official Title
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Short-term Efficacy of a Single Ultrasound-guided Intra-articular Injection of Botulinum Toxin A Associated With Splinting for Base-of-thumb Osteoarthritis: a Randomized Controlled Double-blind Pilot Study

Conditions
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Base-of-thumb Osteoarthritis

Intervention / Treatment
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* Drug: botulinum toxin A
* Drug: saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old Pain intensity on a self-administered 11-point pain numeric rating scale ≥ 30 Pain involving the base-of-thumb X-ray evidence of base-of-thumb osteoarthritis with at least 2 of the 4 following items involving the trapeziometacarpal joint : osteophytes, joint space narrowing, subchondral bone sclerosis or subchondral cysts 1990 American College of Rheumatology classification criteria for hand osteoarthritis adapted to base-of-thumb osteoarthritis Medical examination Written consent Health insurance For women of childbearing age, a negative urinary pregnancy test Exclusion Criteria: History of thumb surgery History of inflammatory or crystal-associated rheumatic disease Neurological disorders involving the hands other than carpien canal syndrom Collagen disorders involving the hands : Dupuytren, Marfan or Ehlers-Danlos diseases Osteoarthritis predominating at the scaphotrapezial joint on X-Ray Hand or wrist trauma ≤ 2 months Hand or wrist intra-articular injections ≤ 2 months Contra-indication to botulinum toxin A injection or to splinting Cognitive or behavioral disorders making the assessment impossible Participant unable to speak, read and write french Bilateral BTOA without predominant symptomatic side Pregnancy and breast feeding Persons referred to in Articles L 1121-5; 6; 8; 9 of the Public Health Code (protected minors or adults, guardianship or trusteeship, etc.) Patient with epilepsy

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intra-articular botulinum toxin A and splinting<br>Ultrasound-guided injection of 50 Allergan Unities of botulinum toxin A (Botox®, Allergan) resuspended in 1 ml of saline in the trapeziometacarpal joint and custom-made thermoformed plastic splint to be worn for 48 hours after intra-articular injection then nightly | Drug: botulinum toxin A<br>* Ultrasound-guided injection of 50 Allergan Unities of botulinum toxin A (Botox®, Allergan) resuspended in 1 ml of saline in the trapeziometacarpal joint and custom-made thermoformed plastic splint to be worn for 48 hours after intra-articular injection then nightly<br>* Other names: Allergan;|
| Active Comparator: Intra-articular saline and splinting<br>Ultrasound-guided injection of 1 ml of saline in the trapeziometacarpal joint and custom-made thermoformed plastic splint to be worn for 48 hours after intra-articular injection then nightly | Drug: saline<br>* Ultrasound-guided injection of 1 ml of saline in the trapeziometacarpal joint and custom-made thermoformed plastic splint to be worn for 48 hours after intra-articular injection then nightly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in base-of-thumb pain 3 months post-injection | Mean change from baseline in average base-of-thumb pain intensity in the previous 48 hrs on a self-administered 11-point pain numeric rating scale (0 no pain - 100 maximal pain) | 3 months post injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in base-of-thumb pain 1 month post-injection | Mean change from baseline in average base-of-thumb pain intensity in the previous 48 hrs on a self-administered 11-point pain numeric rating scale (0 no pain - 100 maximal pain) | 1 month post injection | 
| Change in base-of-thumb pain 6 months post-injection | Mean change from baseline in average base-of-thumb pain intensity in the previous 48 hrs on a self-administered 11-point pain numeric rating scale (0 no pain - 100 maximal pain) | 6 months post injection | 
| Change in hand function 3 months post-injection | Mean change from baseline in average hand-specific limitations in activities in the previous 2 weeks on the self-administered Cochin Hand Function Scale (0 no limitations - 90 maximal limitations) | 3 months post injection | 
| Change in hand function 6 months post-injection | Mean change from baseline in average hand-specific limitations in activities in the previous 2 weeks on the self-administered Cochin Hand Function Scale (0 no limitations - 90 maximal limitations) | 6 months post injection | 
| Change in patient's global assessment 3 months post-injection | Mean change from baseline in patient's global assessment on a self-administered 11-point numeric rating scale (0 worst possible - 100 best possible) | 3 months post-injection | 
| Change in patient's global assessment 6 months post-injection | Mean change from baseline in patient's global assessment on a self-administered 11-point numeric rating scale (0 worst possible - 100 best possible) | 6 months post-injection | 
| Percentage of OARSI responders 3 months post-injection | OARSI response is defined as an improvement in pain (0 to 100 numeric rating scale) or in function (0 to 90 Cochin Hand Function Scale) ≥ 50% and absolute change ≥ 20/100 on pain numeric rating scale or ≥ 9/90 on Cochin Hand Function Scale respectively , or improvement in at least 2 of the 3 following items: 1/ pain ≥ 20% and absolute change ≥ 10/100, 2/ function ≥ 20% and absolute change ≥ 9/90, 3/ patient's global assessment (0 to 100 numeric rating scale) ≥ 20% and absolute change ≥ 10/100 | 3 months post-injection | 
| Percentage of OARSI responders 6 months post-injection | OARSI response is defined as an improvement in pain (0 to 100 numeric rating scale) or in function (0 to 90 Cochin Hand Function Scale) ≥ 50% and absolute change ≥ 20/100 on pain numeric rating scale or ≥ 9/90 on Cochin Hand Function Scale respectively , or improvement in at least 2 of the 3 following items: 1/ pain ≥ 20% and absolute change ≥ 10/100, 2/ function ≥ 20% and absolute change ≥ 9/90, 3/ patient's global assessment (0 to 100 numeric rating scale) ≥ 20% and absolute change ≥ 10/100 | 6 months post-injection | 
| Analgesics consumption at 3 months | Self-reported consumption of analgesics (non-opioid, weak and strong opioids) using a self-administered 4-class scale (never; several times a month; several times a week; daily) | from injection to 3 months post-injection | 
| Analgesics consumption at 6 months | Self-reported consumption of analgesics (non-opioid, weak and strong opioids) using a self-administered 4-class scale (never; several times a month; several times a week; daily) | from 3 to 6 months post-injection | 
| Non-steroidal anti-inflammatory drugs consumption at 3 months | Self-reported consumption of non-steroidal anti-inflammatory drugs using a self-administered 4-class scale (never; several times a month; several times a week; daily) | from injection to 3 months post-injection | 
| Non-steroidal anti-inflammatory drugs consumption at 6 months | Self-reported consumption of non-steroidal anti-inflammatory drugs using a self-administered 4-class scale (never; several times a month; several times a week; daily) | from 3 to 6 months post-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Base-of-thumb osteoarthritis, Botulinum toxin A, Intra-articular therapy, Randomized trial