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

NCT ID: NCT03935295

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-03

Study Completion Date

2026-03-31

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

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.

Conditions

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Adolescent Idiopathic Scoliosis

Keywords

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AIS adolescent idiopathic scoliosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

AbobotulinumtoxinA

Intervention Type DRUG

Paraspinal abobotulinumtoxinA injections (compared to placebo)

Custom Thoracolumbosacral Orthosis

Intervention Type DEVICE

Non-operative external bracing for scoliosis curves

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.

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

Placebo prepared by Ipsen for use as control

Custom Thoracolumbosacral Orthosis

Intervention Type DEVICE

Non-operative external bracing for scoliosis curves

Interventions

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AbobotulinumtoxinA

Paraspinal abobotulinumtoxinA injections (compared to placebo)

Intervention Type DRUG

Placebos

Placebo prepared by Ipsen for use as control

Intervention Type DRUG

Custom Thoracolumbosacral Orthosis

Non-operative external bracing for scoliosis curves

Intervention Type DEVICE

Other Intervention Names

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Dysport, Ipsen

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
Minimum Eligible Age

10 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Sponseller, MD, MBA

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Hospital Department of Orthopaedic Surgery

Varun Puvanesarajah, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins Hospital Department of Orthopaedic Surgery

Locations

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Johns Hopkins University

Baltimore, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Gabrielle Reichard, MA

Role: CONTACT

Phone: 4105023626

Email: [email protected]

Varun Puvanesarajah, MD

Role: CONTACT

Phone: 9193605646

Email: [email protected]

Facility Contacts

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Varun Puvanesarajah, MD

Role: primary

Gabrielle Reichard, MA

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 23445094 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16759428 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 3810292 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26582623 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24047455 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9240788 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29046898 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19092622 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25657814 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14382561 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 932082 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12544958 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16896864 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26555827 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26165216 (View on PubMed)

Related Links

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Other Identifiers

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IRB00110399

Identifier Type: -

Identifier Source: org_study_id