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

Sponsor

Johns Hopkins University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03935295

Collaborator

(none)

Enrollment

Location

Arms

30.9

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Adolescent Idiopathic Scoliosis	Drug: AbobotulinumtoxinA Drug: Placebos Device: Custom Thoracolumbosacral Orthosis	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 3, 2020

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Botulinum Toxin 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 Paraspinal abobotulinumtoxinA injections (compared to placebo) Other Names: Dysport, Ipsen Device: Custom Thoracolumbosacral Orthosis Non-operative external bracing for scoliosis curves
Placebo Comparator: Placebo 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 Placebo prepared by Ipsen for use as control Device: Custom Thoracolumbosacral Orthosis Non-operative external bracing for scoliosis curves

Arm

Intervention/Treatment

Experimental: Botulinum Toxin

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

Paraspinal abobotulinumtoxinA injections (compared to placebo)

Other Names:

Dysport, Ipsen

Device: Custom Thoracolumbosacral Orthosis

Non-operative external bracing for scoliosis curves

Placebo Comparator: Placebo

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

Placebo prepared by Ipsen for use as control

Device: Custom Thoracolumbosacral Orthosis

Non-operative external bracing for scoliosis curves

Outcome Measures

Primary Outcome Measures

Change in scoliotic curve as assessed by the Major Curve Cobb Angle [Assessed at baseline (time 0), 6 weeks, 4 months, 4 months + 6 weeks, 8 months]
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.

Secondary Outcome Measures

Change in Patient Reported Outcomes [Assessed at baseline (time 0), 6 weeks, 4 months, 4 months + 6 weeks, 8 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 16 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins University	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

Johns Hopkins University

Investigators

Principal Investigator: Paul Sponseller, MD, MBA, Johns Hopkins Hospital Department of Orthopaedic Surgery
Principal Investigator: Varun Puvanesarajah, MD, Johns Hopkins Hospital Department of Orthopaedic Surgery