Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development

Adolescent Idiopathic Scoliosis Clinical Trial

— EARLYBIRD  

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05924347
• Other study ID #: NL82419.041.22
• Status: Recruiting
• Start date: June 16, 2023
• Est. completion date: May 1, 2032

Study information

• Verified date: June 2023
• Source: UMC Utrecht
• Contact: Tom Schlosser
• Phone: +31 88 75 53602
• Email: t.p.c.schlosser[@]umcutrecht.nl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: May 1, 2032
• Est. primary completion date: May 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• 22q11.2 Deletion Syndrome
• Adolescent Idiopathic Scoliosis
• DiGeorge Syndrome
• Scoliosis

Intervention

Diagnostic Test:
• MRI
Longitudinal MRI examination of the thoracic and lumbar spine (T2, T2w, sCT)
• Scolioscan
3D ultrasound of the spine
• Skeletal maturity assessment
At one timepoint, a Hand radiograph is taken for digital skeletal maturity assessment

Locations

Country	Name	City	State
Netherlands	UMC Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	Eindhoven University of Technology

Country where clinical trial is conducted

Netherlands, 

Outcome

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