Vitamin A Deficiency, Idiopathic Scoliosis
Conditions
Brief summary
This study aims to investigate whether vitamin A supplementation can influence spinal curve magnitude in idiopathic scoliosis children and potentially prevent its de novo development.
Detailed description
Idiopathic scoliosis (IS) is the most common structural spinal deformity in children and adolescents. Despite extensive research, its etiology remains largely unknown, resulting in a lack of modifiable targets for prevention or early intervention. Notably, preliminary unpublished data from our pediatric health center indicate a high prevalence (up to 30%) of mild scoliosis among children with vitamin A deficiency. Furthermore, our pilot data suggest a tendency toward vitamin A insufficiency in many children diagnosed with IS. Vitamin A is critical for normal bone growth, embryonic skeletal development, and the maintenance of epithelial tissues. We hypothesize that chronic vitamin A deficiency may represent a modifiable risk factor that contributes to the pathogenesis or progression of IS by disrupting these fundamental processes. This study will be conducted at the Child Health-Spine Wellness Center. Children with idiopathic scoliosis and concurrent vitamin A deficiency or insufficiency will be randomized into one of two groups. The Intervention Group will receive sustained biochemical correction through daily oral vitamin A supplementation (2000 IU) for 6 months, coupled with a standardized nutritional education session. The Control Group will receive an identical nutritional education session but no study-provided supplements, serving as an active comparator that controls for the effects of increased health awareness and general dietary advice. For all children with scoliosis, routine follow-up visits with radiographic assessment will be scheduled at 6-month intervals for at least 24 months to evaluate curve progression. Additionally, children with vitamin A deficiency but without scoliosis at baseline will also be randomized to the same supplementation regimens and will undergo annual scoliosis screening as part of an ongoing provincial health initiative. All participants will undergo serial radiographic and clinical assessments. At the same time, a structured safety monitoring plan will be implemented to prevent and promptly identify both vitamin A deficiency persistence and hypervitaminosis A. Prior to randomization, all caregivers will receive standardized education on the signs and symptoms of both significant vitamin A deficiency (e.g., night blindness, dry eyes) and acute/chronic hypervitaminosis A (e.g., headache, nausea/vomiting, dizziness, blurred vision, skin dryness/peeling). They will be instructed to report any such symptoms immediately to the study team via a dedicated 24-hour contact line. Serum retinol concentration will be measured for all participants at baseline and the 6-month visit. This serves the dual purpose of monitoring adherence in the Long-term. If a participant's serum retinol level exceeds 1.0 mg/L, the study supplementation will be immediately suspended, and the participant will be referred to a pediatric nutritionist for further evaluation and management.
Interventions
DIETARY_SUPPLEMENTVitamin A
Vitamin A supplements plus Nutritional Education
BEHAVIORALNutritional Education
Nutritional Education Only
Sponsors
The Children's Hospital of Zhejiang University School of Medicine
Ningbo No. 1 Hospital
Ningbo No.2 Hospital
The Third Affiliated Hospital of Wenzhou Medical University
Second Affiliated Hospital of Wenzhou Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The radiologists measuring Cobb angles will be blinded to treatment allocation.
Eligibility
Sex/Gender
ALL
Age
6 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 6 and 15 years. 2. Biochemically confirmed vitamin A deficiency (serum retinol \< 0.20 mg/L) or insufficiency (serum retinol 0.20-0.29 mg/L). 3. Has undergone radiographic evaluation (standing full-spine X-ray) for idiopathic scoliosis at the initial clinic visit. 4. Skeletally immature (Risser sign 0-3) with a major Cobb angle \< 40 degrees at baseline. 5. Written informed consent/assent provided by the participant and legal guardian.
Exclusion criteria
1. Unwillingness or inability to comply with all study procedures and follow-up visits. 2. Plans to relocate outside the study area within the next 24 months. 3. Previous high-dose vitamin A supplementation therapy within the past 12 months. 4. Clinical signs of severe vitamin A deficiency syndrome (e.g., xerophthalmia, Bitot's spots). 5. Serum vitamin A level \> 0.70 mg/L (to avoid risk of hypervitaminosis A). 6. Severe chronic health conditions that could confound study outcomes, including but not limited to: * Known syndromic, neuromuscular, or congenital musculoskeletal causes of scoliosis. * History of spine surgery or significant spinal trauma. * Spinal tumor. * Leg length discrepancy \> 20 mm. * Other severe chronic diseases (e.g., poorly controlled diabetes, chronic liver or renal disease, malabsorption syndromes). * Severe obesity (body mass index z-score ≥ 3).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Scoliosis Curve Angle | Routine follow-up visits will be scheduled 6 months apart up to 24 months | 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 |
| Angle of Trunk Rotation | Routine follow-up visits will be scheduled 6 months apart up to 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Levels of Vitamin D | At baseline and months 6 | Change in serum concentrations of Vitamin D potentially interacting with vitamin A metabolism or bone health from baseline to 6 months. |
| Scoliosis Research Society-22 (SRS-22) questionnaire | Routine follow-up visits will be scheduled 6 months apart up to 24 months | The SRS-22 aims to evaluate health-related quality of life (HRQOL) in patients with idiopathic scoliosis. The SRS-22 specifically addresses areas affected by spinal deformities-such as pain, self-perception, function, mental health, and satisfaction with treatment. Consequently, it offers a focused approach to understanding the patient experience. |
| Circadian rhythm Measurements | Routine follow-up visits will be scheduled 6 months apart up to 24 months | Circadian rhythm as assessed by Morning and Evening Questionnaire-5 (MEQ-5) |
| Change in Gene Expression Levels of biomarkers | At baseline and months 6 | Change in mRNA expression levels of specific Genes such as HIF1A, Bmal1 and IGFBPs in peripheral blood mononuclear cells (PBMCs) as measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). |
| Change in Serum Vitamin A (Retinol) Level | At baseline and months 6 | Change in serum concentration of retinol (mg/L) measured by high-performance liquid chromatography (HPLC) between baseline and the 6-month visit. |
Countries
China
Contacts
Primary ContactXiangyang Wang, MD
Outcome results
None listed