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

Adolescent Idiopathic Scoliosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03935295
• Other study ID #: IRB00110399
• Status: Recruiting
• Phase: Phase 4
• Start date: September 3, 2020
• Est. completion date: March 31, 2026

Study information

• Verified date: April 2024
• Source: Johns Hopkins University
• Contact: Gabrielle Reichard, MA
• Phone: 4105023626
• Email: greicha1[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

1. 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.

2. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 16 Years

Eligibility

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

Related Conditions & MeSH terms

• Adolescent Idiopathic Scoliosis
• Scoliosis

Intervention

Drug:
• AbobotulinumtoxinA
Paraspinal abobotulinumtoxinA injections (compared to placebo)
• Placebos
Placebo prepared by Ipsen for use as control

Device:
• Custom Thoracolumbosacral Orthosis
Non-operative external bracing for scoliosis curves

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

References & Publications (15)

Asher M, Min Lai S, Burton D, Manna B. The reliability and concurrent validity of the scoliosis research society-22 patient questionnaire for idiopathic scoliosis. Spine (Phila Pa 1976). 2003 Jan 1;28(1):63-9. doi: 10.1097/00007632-200301010-00015. — View Citation

Asher MA, Burton DC. Adolescent idiopathic scoliosis: natural history and long term treatment effects. Scoliosis. 2006 Mar 31;1(1):2. doi: 10.1186/1748-7161-1-2. — View Citation

Cheung KM, Cheng EY, Chan SC, Yeung KW, Luk KD. Outcome assessment of bracing in adolescent idiopathic scoliosis by the use of the SRS-22 questionnaire. Int Orthop. 2007 Aug;31(4):507-11. doi: 10.1007/s00264-006-0209-5. Epub 2006 Aug 1. — View Citation

Fidler MW, Jowett RL. Muscle imbalance in the aetiology of scoliosis. J Bone Joint Surg Br. 1976 May;58(2):200-1. doi: 10.1302/0301-620X.58B2.932082. — View Citation

Hresko MT. Clinical practice. Idiopathic scoliosis in adolescents. N Engl J Med. 2013 Feb 28;368(9):834-41. doi: 10.1056/NEJMcp1209063. No abstract available. — View Citation

Kouwenhoven JW, Castelein RM. The pathogenesis of adolescent idiopathic scoliosis: review of the literature. Spine (Phila Pa 1976). 2008 Dec 15;33(26):2898-908. doi: 10.1097/BRS.0b013e3181891751. — View Citation

Nuzzo RM, Walsh S, Boucherit T, Massood S. Counterparalysis for treatment of paralytic scoliosis with botulinum toxin type A. Am J Orthop (Belle Mead NJ). 1997 Mar;26(3):201-7. — View Citation

RIDDLE HF, ROAF R. Muscle imbalance in the causation of scoliosis. Lancet. 1955 Jun 18;268(6877):1245-7. doi: 10.1016/s0140-6736(55)91020-5. No abstract available. — View Citation

Schwieger T, Campo S, Weinstein SL, Dolan LA, Ashida S, Steuber KR. Body Image and Quality-of-Life in Untreated Versus Brace-Treated Females With Adolescent Idiopathic Scoliosis. Spine (Phila Pa 1976). 2016 Feb;41(4):311-9. doi: 10.1097/BRS.0000000000001210. — View Citation

Weinstein SL, Dolan LA, Wright JG, Dobbs MB. Effects of bracing in adolescents with idiopathic scoliosis. N Engl J Med. 2013 Oct 17;369(16):1512-21. doi: 10.1056/NEJMoa1307337. Epub 2013 Sep 19. — View Citation

Weinstein SL, Dolan LA. The Evidence Base for the Prognosis and Treatment of Adolescent Idiopathic Scoliosis: The 2015 Orthopaedic Research and Education Foundation Clinical Research Award. J Bone Joint Surg Am. 2015 Nov 18;97(22):1899-903. doi: 10.2106/JBJS.O.00330. No abstract available. — View Citation

Weinstein SL. Idiopathic scoliosis. Natural history. Spine (Phila Pa 1976). 1986 Oct;11(8):780-3. doi: 10.1097/00007632-198610000-00006. — View Citation

Wong C, Gosvig K, Sonne-Holm S. The role of the paravertebral muscles in adolescent idiopathic scoliosis evaluated by temporary paralysis. Scoliosis Spinal Disord. 2017 Oct 10;12:33. doi: 10.1186/s13013-017-0138-7. eCollection 2017. — View Citation

Wong C, Pedersen SA, Kristensen BB, Gosvig K, Sonne-Holm S. The Effect of Botulinum Toxin A Injections in the Spine Muscles for Cerebral Palsy Scoliosis, Examined in a Prospective, Randomized Triple-blinded Study. Spine (Phila Pa 1976). 2015 Dec;40(23):E1205-11. doi: 10.1097/BRS.0000000000001049. — View Citation

Wong C. Mechanism of right thoracic adolescent idiopathic scoliosis at risk for progression; a unifying pathway of development by normal growth and imbalance. Scoliosis. 2015 Jan 27;10:2. doi: 10.1186/s13013-015-0030-2. eCollection 2015. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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

External Links

•   Dysport Prescribing Information