Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development (EARLYBIRD)

Longitudinal MRI Study to Catch EARLY Scoliotic Changes of the Bone and Intervertebral Disc in Younger Sisters and Daughters of Adolescent Idiopathic Scoliosis Patients and the 22q11.2DS Population.

Rationale: Despite several decades of research, the exact etiology of adolescent idiopathic scoliosis (AIS) remains unclear. In AIS, spine curvature begins with and progresses during the adolescent growth spurt. Previous studies are only performed on populations with already established scoliosis and normal spinal growth (of bone and IVD tissue) during adolescence has also not been defined. Growth pattern differences may exist between scoliotic and nonscoliotic subjects. Previous studies support the hypothesis that AIS is a spinal deformity that starts with decompensation in the IVD and is linked to sagittal spinal alignment. However, to understand its cause and pathogenic mechanism, the changes to the adolescent spine must be assessed longitudinally during the growth period coinciding with the period prior to and during the onset of AIS. Ideally this should include a cohort who do and do not develop AIS and their assessment must be minimally harmful, without radiation exposure. Certain populations are at increased risk for scoliosis development (i.e. girls with family members with scoliosis and 22q11.2DS patients). New imaging modalities (boneMRI, 3D spinal ultrasound) allow for non-radiographic monitoring of spinal growth.

Study Overview

• Status: Recruiting
• Conditions: 22q11.2 Deletion Syndrome; Adolescent Idiopathic Scoliosis
• Intervention / Treatment: Diagnostic test: MRI; Diagnostic test: Scolioscan; Diagnostic test: Skeletal maturity assessment

Detailed Description

Objective: The primary objectives is: To longitudinally evaluate the substantial differences in anatomical changes in the spine during adolescent growth in girls, at increased risk for scoliosis development, and in adolescent 22q11.2DS patients, that do and do not develop AIS.

The secondary objectives are:

• To develop spine specific (IVD/endplates) maturity assessment grading.
• To implement radiation-free imaging methods for spinal monitoring in adolescent patients at risk for scoliosis development.
• To create a longitudinal dataset for patient specific spinal biomechanical assessment.

Study design: Prospective observational cohort study

Study population: 60 adolescent girls (8-10 years old) at increased risk for idiopathic scoliosis development (an older sibling or parent diagnosed with idiopathic scoliosis) (Cohort-1) and 60 adolescent girls and boys with 22q11.2DS with increased risk for idiopathic-like scoliosis development (Cohort-2).

Intervention: none

Main study parameters/endpoints: Spinal MR imaging of the thoracic and lumbar spine will be performed at 5 time points between 8 or 9 and 15 or 16 for girls and boys respectively to evaluate possible changes in the 3D anatomy of the spine. The main study parameter will be the longitudinal changes in segmental axial rotation on boneMRI of the thoracolumbar spine in subjects that do and do not develop AIS.

Secondary endpoints: Changes in bone and intervertebral disc morphology, lateral shift of the nucleus pulposus. These will be correlated to assessments of growth, skeletal maturity and spinal alignment.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Tom Schlosser; Phone Number: +31 88 75 53602; Email: t.p.c.schlosser@umcutrecht.nl
• Study Contact Backup: Name: Hilde Stempels; Email: h.w.stempels@umcutrecht.nl

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • UMC Utrecht
    • Contact: Tom Schlösser, MD, PhD; Email: t.p.c.schlosser@umcutrecht.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cohort 1: 60 adolescent girls (8-10 years old) at increased risk for idiopathic scoliosis development (an older sibling or parent diagnosed with idiopathic scoliosis) Cohort 2: 60 adolescent girls or boys with the 22q11.2DS with increased risk for idiopathic-like scoliosis development.

Description

Inclusion Criteria:

Cohort 1:

• Female,
• 8, 9 or 10 years old
• An older sibling, twin or parent diagnosed with AIS

Cohort 2:

• Diagnosed with 22q11.2DS
• Girls: 8, 9 or 10 years old.
• Boys: 9, 10 or 11 years old.

All

• No clinical signs of scoliosis at inclusion (physical examination by forward bending test and Bunnell Scoliometer assessment with a cut-off value of 7°.
• Written informed consent of parents/legal representatives.

Exclusion Criteria:

• Contraindications for MR imaging
• Early-onset scoliosis or other spinal deformities
• Other syndromes or neuromuscular disease associated with scoliosis
• Clinical signs of >1cm leg length discrepancy
• Other diseases or injuries, that are related to abnormal spinal growth, posture, activity levels, or scoliosis development.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; 60 adolescent girls (8-10 years old) at increased risk for idiopathic scoliosis development (an older sibling or parent diagnosed with idiopathic scoliosis)	Diagnostic test: MRI; Longitudinal MRI examination of the thoracic and lumbar spine (T2, T2w, sCT); Diagnostic test: Scolioscan; 3D ultrasound of the spine; Diagnostic test: Skeletal maturity assessment; At one timepoint, a Hand radiograph is taken for digital skeletal maturity assessment
Cohort 2; 60 adolescent girls or boys with the 22q11.2DS with increased risk for idiopathic-like scoliosis development.	Diagnostic test: MRI; Longitudinal MRI examination of the thoracic and lumbar spine (T2, T2w, sCT); Diagnostic test: Scolioscan; 3D ultrasound of the spine; Diagnostic test: Skeletal maturity assessment; At one timepoint, a Hand radiograph is taken for digital skeletal maturity assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Girls: Baseline
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Girls: 11year
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Girls: 12year
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Girls: 13year
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Girls: 15year
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Boys: Baseline
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Boys: 12year
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Boys: 13year
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Boys: 14year
Spinal MR Imaging of the thoracic and lumbar spine	MRI images	Boys: 16year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Girls: Baseline
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Girls: 11year
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Girls: 12year
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Girls: 13year
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Girls: 15year
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Boys: Baseline
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Boys: 12year
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Boys: 13year
A-P ratio vertebrae and disc	Ratio anterior and posterior height	Boys: 14year
A-P ratio vertebrae	Ratio anterior and posterior height	Boys: 16year
Left-right ratio	Ratio left and right height	Girls: Baseline
Left-right ratio	Ratio left and right height	Girls: 11year
Left-right ratio	Ratio left and right height	Girls: 12year
Left-right ratio	Ratio left and right height	Girls: 13year
Left-right ratio	Ratio left and right height	Girls: 15year
Left-right ratio	Ratio left and right height	Boys: Baseline
Left-right ratio	Ratio left and right height	Boys: 12year
Left-right ratio	Ratio left and right height	Boys: 13year
Left-right ratio	Ratio left and right height	Boys: 14year
Left-right ratio	Ratio left and right height	Boys: 16year
Torsion	Difference in axial rotation between 2 subsequent endplates	Girls: Baseline
Torsion	Difference in axial rotation between 2 subsequent endplates	Girls: 11year
Torsion	Difference in axial rotation between 2 subsequent endplates	Girls: 12year
Torsion	Difference in axial rotation between 2 subsequent endplates	Girls: 13year
Torsion	Difference in axial rotation between 2 subsequent endplates	Girls: 15year
Torsion	Difference in axial rotation between 2 subsequent endplates	Boys: Baseline
Torsion	Difference in axial rotation between 2 subsequent endplates	Boys: 12year
Torsion	Difference in axial rotation between 2 subsequent endplates	Boys: 13year
Torsion	Difference in axial rotation between 2 subsequent endplates	Boys: 14year
Torsion	Difference in axial rotation between 2 subsequent endplates	Boys: 16year
Volumes disc	Volumes disc	Girls: Baseline
Volumes disc	Volumes disc	Girls: 11year
Volumes disc	Volumes disc	Girls: 12year
Volumes disc	Volumes disc	Girls: 13year
Volumes disc	Volumes disc	Girls: 15year
Volumes disc	Volumes disc	Boys: Baseline
Volumes disc	Volumes disc	Boys: 12year
Volumes disc	Volumes disc	Boys: 13year
Volumes disc	Volumes disc	Boys: 14year
Volumes disc	Volumes disc	Boys: 16year
Volumes vertebrae	Volumes vertebrae	Girls: Baseline
Volumes vertebrae	Volumes vertebrae	Girls: 11year
Volumes vertebrae	Volumes vertebrae	Girls: 12year
Volumes vertebrae	Volumes vertebrae	Girls: 13year
Volumes vertebrae	Volumes vertebrae	Girls: 15year
Volumes vertebrae	Volumes vertebrae	Boys: Baseline
Volumes vertebrae	Volumes vertebrae	Boys: 12year
Volumes vertebrae	Volumes vertebrae	Boys: 13year
Volumes vertebrae	Volumes vertebrae	Boys: 14year
Volumes vertebrae	Volumes vertebrae	Boys: 16year
Shift nucleus pulposis	Position of nucleus pulposus in discus	Girls: Baseline
Shift nucleus pulposis	Position of nucleus pulposus in discus	Girls: 11year
Shift nucleus pulposis	Position of nucleus pulposus in discus	Girls: 12year
Shift nucleus pulposis	Position of nucleus pulposus in discus	Girls: 13year
Shift nucleus pulposis	Position of nucleus pulposus in discus	Girls: 15year
Shift nucleus pulposis	Position of nucleus pulposus in discus	Boys: Baseline
Shift nucleus pulposis	Position of nucleus pulposus in discus	Boys: 12year
Shift nucleus pulposis	Position of nucleus pulposus in discus	Boys: 13year
Shift nucleus pulposis	Position of nucleus pulposus in discus	Boys: 14y
Shift nucleus pulposis	Position of nucleus pulposus in discus	Boys: 16year
Changes in spinal alignment during growth	Scan for changes over growth	Girls: Baseline-15years, Boys: Baseline-15years
Spine specific maturity assessment grading	See if it is possible to create a spine specific maturity assessment	Girls: Baseline-15years, Boys: Baseline-15years

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: Eindhoven University of Technology

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2023
• Primary Completion (Estimated): May 1, 2032
• Study Completion (Estimated): May 1, 2032

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 20, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Lymphatic Diseases; Endocrine System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Parathyroid Diseases; Spinal Diseases; Bone Diseases; Spinal Curvatures; Heart Defects, Congenital; Cardiovascular Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Abnormalities, Multiple; Chromosome Disorders; 22q11 Deletion Syndrome; Lymphatic Abnormalities; Hypoparathyroidism; Scoliosis; DiGeorge Syndrome
• Other Study ID Numbers: NL82419.041.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No