Dysport ® as an Adjunctive Treatment to Bracing in the Management of Adolescent Idiopathic Scoliosis

Study Overview
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Brief Summary
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This study evaluates the combined effect of botulinum toxin A (administered as Dysport® (Ipsen Pharmaceuticals)) and bracing in children with adolescent idiopathic scoliosis. Two thirds of patients will be treated with Dysport® and bracing, while the remaining patients will be treated with placebo and bracing.

Detailed Description
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Adolescent idiopathic scoliosis (AIS) is lateral curvature of the spine with an unknown cause in children 10-16 years old. Without treatment, skeletally immature children with idiopathic curves of 20°-40° risk curve progression. Treatment of these patients is focused on either observation or bracing. Although bracing has been shown to be more effective than observation, success is contingent on patient adherence and has the potential for further optimization with adjunct therapies. Little research is available concerning adjunct therapies that may be used during bracing of AIS patients. One therapy in particular, abobotulinumtoxinA (BTX) injection, has been poorly studied. Injection of BTX into the paraspinal musculature of the concave aspect of the major curve may result in a more malleable curve and thus optimize brace treatment. If BTX injections are found to improve outcomes in this way, a new standard of nonoperative care could be established for AIS patients, potentially reducing the number of patients who undergo surgery. The aim of this study is to assess whether BTX injections (administered as Dysport® (Ipsen Pharmaceuticals)) in the paraspinal musculature at the site of the major scoliotic curve decrease curve progression in skeletally immature AIS patients who are concurrently treated with bracing. Dysport® will be evaluated primarily as an adjunct treatment to bracing. Hypotheses Dysport® injections into the concave-side paraspinal muscles will decrease the rate of curve progression, with a lower rate of curve progression in patients treated with both Dysport® injections and bracing compared with those treated with only bracing. Quantitative physical and mental health scores will improve to a greater extent in patients treated with Dysport® and bracing compared with patients treated with only bracing.

Official Title
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Dysport ® (abobotulinumtoxinA) as an Adjunctive Treatment to Bracing in the Management of Adolescent Idiopathic Scoliosis

Conditions
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Adolescent Idiopathic Scoliosis

Intervention / Treatment
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* Drug: AbobotulinumtoxinA
* Drug: Placebos
* Device: Custom Thoracolumbosacral Orthosis


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Clinically determined idiopathic nature of scoliosis Age 10-16 years Risser stage 0,1,or 2 major curve of 20°-40° curve apex caudal to T7 vertebra ability to adhere to bracing protocol Botulinum toxin naïve or previously treated greater than 6 months prior to study entry Exclusion criteria: Diagnosis of congenital scoliosis, neuromuscular scoliosis, or other reason for scoliosis - Previous surgery at any segment of the spine Current need for surgery at any level of the spine Treatment with any drug known to interfere with neuromuscular function Any other medical condition, laboratory or diagnostic procedure finding that might preclude administration of BTX Ongoing infection at the injection sites Diagnosis as either resistant or sensitive to botulinum toxin treatment of any type or to any components of the BTX formulation Cow milk protein allergy

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 16 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<br>The investigators plan to administer approximately 1000 U Dysport ® in the concave-sided paraspinal musculature of the major curve, based on an estimated total dose of 1000 U, the maximum allowable dose. The total dose per treatment session will not exceed 15 units/kilogram or 1000 units, whichever is lower. If two curves are equivalent within 3˚, both will be treated, however, the dosing (described above) will be divided equally across both curves. There will be two cycles of injections. Patients will be treated at time 0 (baseline) and 4 months. | Drug: AbobotulinumtoxinA<br>* Paraspinal abobotulinumtoxinA injections (compared to placebo)<br>* Other names: Dysport, Ipsen;Device: Custom Thoracolumbosacral Orthosis<br>* Non-operative external bracing for scoliosis curves<br>|
| Placebo Comparator: Placebo<br>Control patients will receive an injection of placebo specifically prepared as a control for this study. The same volumes as indicated in the experimental arm description will be injected. These will be administered during two cycles of injections. Patients will be treated at time 0 (baseline) and 4 months. | Drug: Placebos<br>* Placebo prepared by Ipsen for use as control<br>Device: Custom Thoracolumbosacral Orthosis<br>* Non-operative external bracing for scoliosis curves<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in scoliotic curve as assessed by the Major Curve Cobb Angle | Change in scoliotic curve will be assessed using by the Major Curve Cobb Angle with measurement of standing scoliosis radiographs. Cobb angle refers to a radiographic measurement of side to side spinal curvature, measured in angle degrees. | Assessed at baseline (time 0), 6 weeks, 4 months, 4 months + 6 weeks, 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Patient Reported Outcomes | This will be assessed by Scoliosis Research Society (SRS) 22 Survey; The SRS-22 questionnaire is a validated measure used to assesses quality of life in patients with idiopathic scoliosis. It consists of five domains that assess: function, pain, mental health, self-image, and satisfaction with treatment. Higher scores indicate increased satisfaction. Each of the 22 questions are scored on a scale of 1 to 5. | Assessed at baseline (time 0), 6 weeks, 4 months, 4 months + 6 weeks, 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIS, adolescent idiopathic scoliosis