Clinical trial NCT05924347: Early Scoliotic Changes in Children at Increased Risk for Scoliosis Development
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.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Adolescent Idiopathic Scoliosis
22q11.2 Deletion Syndrome
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Eindhoven University of Technology
First posted: 2023-06-29
Enrollment: 120
Sex: ALL
Minimum age (years): 8
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Girls: Baseline
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Girls: 11year
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Girls: 12year
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Girls: 13year
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Girls: 15year
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Boys: Baseline
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Boys: 12year
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Boys: 13year
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Boys: 14year
measure: Spinal MR Imaging of the thoracic and lumbar spine
timeFrame: Boys: 16year
Secondary outcomes:
measure: A-P ratio vertebrae and disc
timeFrame: Girls: Baseline
measure: A-P ratio vertebrae and disc
timeFrame: Girls: 11year
measure: A-P ratio vertebrae and disc
timeFrame: Girls: 12year
measure: A-P ratio vertebrae and disc
timeFrame: Girls: 13year
measure: A-P ratio vertebrae and disc
timeFrame: Girls: 15year
measure: A-P ratio vertebrae and disc
timeFrame: Boys: Baseline
measure: A-P ratio vertebrae and disc
timeFrame: Boys: 12year
measure: A-P ratio vertebrae and disc
timeFrame: Boys: 13year
measure: A-P ratio vertebrae and disc
timeFrame: Boys: 14year
measure: A-P ratio vertebrae
timeFrame: Boys: 16year
measure: Left-right ratio
timeFrame: Girls: Baseline
measure: Left-right ratio
timeFrame: Girls: 11year
measure: Left-right ratio
timeFrame: Girls: 12year
measure: Left-right ratio
timeFrame: Girls: 13year
measure: Left-right ratio
timeFrame: Girls: 15year
measure: Left-right ratio
timeFrame: Boys: Baseline
measure: Left-right ratio
timeFrame: Boys: 12year
measure: Left-right ratio
timeFrame: Boys: 13year
measure: Left-right ratio
timeFrame: Boys: 14year
measure: Left-right ratio
timeFrame: Boys: 16year
measure: Torsion
timeFrame: Girls: Baseline
measure: Torsion
timeFrame: Girls: 11year
measure: Torsion
timeFrame: Girls: 12year
measure: Torsion
timeFrame: Girls: 13year
measure: Torsion
timeFrame: Girls: 15year
measure: Torsion
timeFrame: Boys: Baseline
measure: Torsion
timeFrame: Boys: 12year
measure: Torsion
timeFrame: Boys: 13year
measure: Torsion
timeFrame: Boys: 14year
measure: Torsion
timeFrame: Boys: 16year
measure: Volumes disc
timeFrame: Girls: Baseline
measure: Volumes disc
timeFrame: Girls: 11year
measure: Volumes disc
timeFrame: Girls: 12year
measure: Volumes disc
timeFrame: Girls: 13year
measure: Volumes disc
timeFrame: Girls: 15year
measure: Volumes disc
timeFrame: Boys: Baseline
measure: Volumes disc
timeFrame: Boys: 12year
measure: Volumes disc
timeFrame: Boys: 13year
measure: Volumes disc
timeFrame: Boys: 14year
measure: Volumes disc
timeFrame: Boys: 16year
measure: Volumes vertebrae
timeFrame: Girls: Baseline
measure: Volumes vertebrae
timeFrame: Girls: 11year
measure: Volumes vertebrae
timeFrame: Girls: 12year
measure: Volumes vertebrae
timeFrame: Girls: 13year
measure: Volumes vertebrae
timeFrame: Girls: 15year
measure: Volumes vertebrae
timeFrame: Boys: Baseline
measure: Volumes vertebrae
timeFrame: Boys: 12year
measure: Volumes vertebrae
timeFrame: Boys: 13year
measure: Volumes vertebrae
timeFrame: Boys: 14year
measure: Volumes vertebrae
timeFrame: Boys: 16year
measure: Shift nucleus pulposis
timeFrame: Girls: Baseline
measure: Shift nucleus pulposis
timeFrame: Girls: 11year
measure: Shift nucleus pulposis
timeFrame: Girls: 12year
measure: Shift nucleus pulposis
timeFrame: Girls: 13year
measure: Shift nucleus pulposis
timeFrame: Girls: 15year
measure: Shift nucleus pulposis
timeFrame: Boys: Baseline
measure: Shift nucleus pulposis
timeFrame: Boys: 12year
measure: Shift nucleus pulposis
timeFrame: Boys: 13year
measure: Shift nucleus pulposis
timeFrame: Boys: 14y
measure: Shift nucleus pulposis
timeFrame: Boys: 16year
measure: Changes in spinal alignment during growth
timeFrame: Girls: Baseline-15years, Boys: Baseline-15years
measure: Spine specific maturity assessment grading
timeFrame: Girls: Baseline-15years, Boys: Baseline-15years
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
References: