Idiopathic Scoliosis New Onset and Melatonin Phase Delay in Children

Melatonin Phase Delay May Increase Risk of Children and Adolescent Idiopathic Scoliosis.

This study aimed to investigate the prevalence and clinical significance of melatonin phase delay in children with new onset and progressive idiopathic scoliosis (IS).

Study Overview

• Status: Recruiting
• Conditions: Scoliosis Idiopathic; Circadian Rhythm; Melatonin

Detailed Description

Scoliosis is a three-dimensional (3D) structural deformity of the spine defined as a radiological lateral curvature of the spine in the coronal plane of ≥10°. The worldwide prevalence of spinal curves ranges from 0.5% to 5% in children aged 10-16 years. The aetiopathogenesis of idiopathic scoliosis includes genetic abnormalities, neuromuscular, biomechanics, bone metabolism, hormonal factors, and lifestyle explorations. However, none of these factors has been established conclusively as a direct cause of IS.

Etiological research is crucial for the treatment and prevention of idiopathic scoliosis (IS). "Melatonin deficiency" was once one of the most promising etiological hypotheses for IS. Blood melatonin deficiency and dysfunction of its signaling pathways are widely suspected to play a significant role in adolescent idiopathic scoliosis (AIS). In 1994, Machida et al were the first to discover that melatonin deficiency caused by pinealectomy could induce changes similar to idiopathic scoliosis in chickens. Bipedal mice (standing and walking on hind limbs) that underwent pinealectomy or bipedal C57BL/6 mice naturally lacking melatonin were subsequently shown to develop scoliosis as well.

However, the relationship between circulating melatonin levels and AIS in human adolescents has shown significant discrepancies among studies. Whether IS patients have a melatonin deficiency remains to be seen. While Ahuja et al found that daytime melatonin levels in AIS patients were lower than those in normal controls, most other researchers reported no significant differences in serum melatonin, urinary melatonin metabolite levels during the day and night between IS patients and controls. Goultidis et al. even found that melatonin levels in AIS patients were higher than those in the control group. Current studies only measure melatonin concentration. The impact of changes in melatonin secretion patterns on scoliosis has not yet been reported. Our cross-sectional study found that the onset and peak of melatonin secretion were both delayed in patients with scoliosis compared to the control group. The delayed melatonin secretion could be a potential cause of scoliosis.

To fill those gaps, investigators will perform a prospective, unrandomized, observational cohort study at a scoliosis center to determine the prevalence and significance of melatonin phase delay in children with IS. All subjects underwent scoliosis screening led by the Zhejiang Provincial Government. Those with a scoliometer-measured ATR > 5 degrees and a Cobb angle > 10 degrees on X-ray were diagnosed with scoliosis. Individuals with an ATR > 5 degrees but a Cobb angle < 10 degrees on X-ray, or an ATR < 5 degrees, were classified as normal. Subjects screened with the Morning and Evening Questionnaire-5 (MEQ-5), the Pediatric Sleep Questionnaire (PSQ), and the Pittsburgh Sleep Quality Index (PSQI) are used to assess circadian rhythm and sleep quality. Routine follow-up visits will be scheduled 6 months apart up to at least 36 months to assess the new onset scoliosis. Patients diagnosed with scoliosis underwent X-ray examinations, while those not diagnosed with scoliosis were uniformly screened for scoliosis in Zhejiang Province during 2024-2027

• Study Type: Observational
• Enrollment (Estimated): 956

Contacts and Locations

• Study Contact: Name: Xiangyang Wang, MD; Phone Number: 86-13506663458; Email: Xiangyangwang@wmu.edu.com
• Study Contact Backup: Name: Chongan Huang, MD; Phone Number: 86-577-88006815; Email: huangchongan@126.com

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The Second Affiliated Hospital of Wenzhou Medical University
      • Contact: Chongan Huang, MD; Phone Number: 86-577-88006815; Email: huangchongan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

• Patients with scoliosis other than idiopathic, or with other musculoskeletal or neurodevelopmental conditions that might be responsible for the scoliosis
• History of previous spine surgery or spinal injury
• Tumor or malignant tumor in the spine and brain
• Leg length discrepancy more than 20 mm
• Fail to fulfill the questionnaire or refuse to attend any further evaluation
• Plans to relocate within the next 24 months

Description

Inclusion Criteria:

• Collect saliva according to standards and complete melatonin testing

  • Complete scoliometer or X-ray assess scoliosis
  • Skeletally immature (Risser Sign 0-3)
  • Age between 6 and 15
  • Patients can understand and complete the MEQ-5, PSQ, and PSQI Questionnaire at baseline and follow-up visits
  • Informed Consent Form signed by subject or the guardian

Exclusion Criteria:

-

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Melatonin phase delay; Salivary melatonin testing shows Melatonin phase delay
Melatonin phase nromal, controls; Salivary melatonin testing shows normal, control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scoliosis Curve Angle	A long standard standing whole spine radiograph will be used for measuring curve size in terms of Cobb angle according to the standard Cobb method	Routine follow-up visits will be scheduled 6 months apart up to 36 months
Angle of Trunk Rotation	In addition to spinal X-rays, a Scoliometer can also help monitor curve progression. The Scoliometer is an inclinometer that measures the asymmetries between the sides of the trunk by measuring axial rotation in degrees. Numerous studies have found a high correlation between trunk axial rotation (ATR) values and the Cobb angles.	Routine follow-up visits will be scheduled 6 months apart up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body mass index	Changes in height, weight and body mass index	Routine follow-up visits will be scheduled 6 months apart up to 36 months
Circadian rhythm Measurements	circadian rhythm as assessed by Morning and Evening Questionnaire-5 (MEQ-5)	Baseline
Sleep quality	The Pediatric Sleep Questionnaire (PSQ) is used to assess sleep quality	Baseline
Sleep quality	The Pittsburgh Sleep Quality Index (PSQI) is used to assess sleep quality	Baseline

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Wenzhou Medical University
• Investigators: Study Chair: Aimin Wang, MD, Second Affiliated Hospital of Wenzhou Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 15, 2027

Study Registration Dates

• First Submitted: June 28, 2024
• First Submitted That Met QC Criteria: July 14, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 14, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Melatonin; Scoliosis
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Spinal Curvatures; Scoliosis
• Other Study ID Numbers: SAHoWMU-CR2024-08-215

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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