Effects of Intraarticular Botulinum Toxin A in Ankle Osteoarthritis

Study Overview
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Brief Summary
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The purpose of this study is to compare the effects of intraarticular Botulinum Toxin A versus intraarticular hyaluronate plus rehabilitation exercise in patients with ankle osteoarthritis.

Detailed Description
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Recent pilot studies report that intraarticular injection of Botulinum Toxin A into painful joints of patients with various types of arthritis leads to significant and durable improvement in pain and function and is safe to use. To date, there is no published literature that evaluate the effects of intraarticular Botulinum Toxin A in the treatment of ankle OA. Sun el al reported that 3 or 5 weekly injection of hyaluronate may improve pain and physical function in patients with ankle OA and the treatment effects may last for 6 months. The effect of one injection of hyaluronate plus exercise had never been studied. The purpose of this study is to compare the effects of intraarticular Botulinum Toxin A versus intraarticular hyaluronate plus rehabilitation exercise for patients with ankle OA.

Official Title
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Comparing Effects of Intraarticular Botulinum Toxin A Versus Hyaluronate Plus Rehabilitation Exercise in Patients With Unilateral Ankle Osteoarthritis

Conditions
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Ankle Osteoarthritis

Intervention / Treatment
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* Drug: Botulinum Toxin A (Allergan, Inc, Irvine CA)
* Drug: Hyalgan (Hyalgan, Fidia , Italy)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: an age of 20-85 years with diagnosis of ankle osteoarthritis unilateral ankle pain that had lasted for at least 6 months, with no significant benefit from conservative treatment or with an inability to tolerate the side effects of medications ankle radiographs taken within 6 months equivalent to grade 2 on the Kellgren-Lawrence grading system a current total Ankle Osteoarthritis Scale (AOS) score of >3 and < 9 (possible range, 0-10) a normal activity level-i.e., not bedridden or confined to a wheelchair, and are able to walk 30 meters without the aid of a walker, crutches or cane no changes in shoes or orthotic devices during the study period. Exclusion Criteria: pregnancy or lactation in women lower leg trauma other than ankle trauma previous surgery involving the spine, hip or knee the presence of an active joint infections of foot or ankle previous surgery or arthroscopy on the ankle within 12 months history of chicken or egg allergy intraarticular steroid or hyaluronate injection in the treated ankle within the previous 6 months treatment with anticoagulants or immunosuppressives a history of rheumatoid arthritis, gout, or any other inflammatory arthropathy the presence of other comorbidity (such as neoplasms, diabetes mellitus, paresis or recent trauma) or poor health status that would interfere with the clinical assessments during the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 85 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: The Botulinum Toxin A group<br>The Botulinum Toxin A group received intraarticular injections of 100 units of Botulinum Toxin A (Allergan, Inc, Irvine CA) reconstituted in 2 cc normal saline. | Drug: Botulinum Toxin A (Allergan, Inc, Irvine CA)<br>* patients received intraarticular injections by the same experienced physician using aseptic procedures.<br>* Other names: 100 units of Botulinum Toxin A in 2 cc NS;|
| Active Comparator: The hyaluronate group (Hyalgan, Italy)<br>The hyaluronate group received intraarticular injections of 2 ml sodium hyaluronate (Hyalgan, molecular weight 500-730kDa, Fidia Pharmaceutical Corporation, Abano Terme, Italy) and subsequent 6 sessions of rehabilitation exercise for 50 miniutes/day, 3 days per week for 2 weeks and home exercise for 2 weeks . | Drug: Hyalgan (Hyalgan, Fidia , Italy)<br>* The rehabilitation program consists of 6 sessions of rehabilitation exercise for 50 miniutes/day, 3 days per week for 2 weeks and home exercise program for another 2 weeks.<br>* Other names: 2 ml Hyalgan, molecular weight 500-730kDa, Fidia , Italy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ankle Osteoarthritis Scale (AOS) score | The AOS is a patient-rated, validated outcome measure that includes nine items on a pain subscale and nine items on a disability subscale.Using the AOS, a score of 0 represent no pain or disability and 10 represent worst pain or disability imaginable | at 6 months after the injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AOFAS ankle/hindfoot score | AOFAS ankle/hindfoot score is a 100-point scale that devotes 40 points to pain, 50 points to function and 10 points to alignment. | pre-injection and at 2 weeks, 1 month, 3 months, and 6 months post injection. | 
| Visual analog scale (VAS) | The patient rate the intensity of average ankle movement pain in the previous week using a 10-cm horizontal Visual analog scale (VAS) | pre-injection and at 2 weeks, 1 month, 3 months, and 6 months post injection | 
| Single-leg stance test (SLS) | Single-leg stance test (SLS) is done by raising one foot up without touching it to the supported lower extremity with ankle OA and maintain balance for as long as possible | pre-injection and at 2 weeks, 1 month, 3 months, and 6 months post injection | 
| Timed  Up-and-Go test (TUG) | A Timed  Up-and-Go test (TUG) measures functional mobility and the dynamic balance of an individual. | pre-injection and at 2 weeks, 1 month, 3 months, and 6 months post injection | 
| global Patients satisfaction | This rating is based on a 7-point categorical scale ranging from completely satisfied, satisfied, somewhat satisfied, no change, somewhat unsatisfied, unsatisfied to completely unsatisfied. | at 2 weeks, 1 month, 3 months, and 6 months post injection. | 
| adverse effects | patients recorded any systemic and local adverse effects (defined as any unwanted effect whether it was thought to be related to the study or not) on a diary card. | at 2 weeks, 1 month, 3 months, and 6 months post injection. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoarthritis, botulinum toxin, hyaluronate