Monthly Boluses Versus Daily Doses for Correcting Blood Vitamin D Deficit in Obese Children and Adolescents

Study Overview
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Brief Summary
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Childhood obesity prevalence is increasing and is a serious public health challenge. Indeed, according to INPES in 2006, overweight and obesity were affecting 18 % of French children between 3 and 17 years. 3 % of the boys and 4 % of the girls were classified as obese. Obese children are likely to develop chronic disease, starting at paediatric age, as cardiovascular or bone diseases, or type 2 diabetes. Vitamin D deficiency is recognized to play an essential role in bone metabolism and arterial hypertension and type 2 diabetes development. Obesity, in adults like in children, is associated with vitamin D deficiency. Common explanations for this low serum concentration of 25(OH)D in obese are the sequestration and/or the volumetric dilution of this lipid-soluble vitamin by adipose tissue. Therefore, obese population is at higher risk of developing cardiovascular and metabolic complications. The nutrition comity of French Pediatric Society (SFP) edit vitamin D supplementation recommendations (2012) for adolescents at risk of deficit: supplementation by trimestral loading dose of 80 000 to 100 000 UI of vitamin D. However, for obese patients, the deficit is difficult to cure with classical loading doses. It seems that these patients need higher dose of Vitamin D (two to three times higher). Likewise, the optimum scheme of administration (daily vs monthly) was never evaluated. Given new physiopathological data on pleiotropic role of vitamin D (on bone, cardiovascular system, adipose tissue) and in light of consequence of obesity on these systems, it seems essential to obtain data on vitamin deficit correction in obese children and adolescents and to evaluate bone status of these patients using modern imaging technics (high resolution peripheral quantitative computed tomography, HRpQCT). In this context, the OBEVIDOS study, randomised multi-centre prospective in 156 obese children and adolescent will allow us for : evaluate vitamin D correction effect by two scheme of administration establish an inventory of vitamin D status in this population Modeling and simulation of vitamin D concentration in obese children and adolescents using a mathematical PBPK model study, in a patient sub-group, the impact of vitamin D deficit and of obesity by itself on bone, by analysing bone micro-architecture

Official Title
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Treatment of Vitamin D Deficit in Obese Children and Adolescents: a Multi-centre Open Label Randomized Controlled Study Comparing the Efficacy of Two Oral Supplementation Regimens: Monthly Boluses Versus Daily Doses for Correcting Blood Vitamin D Level. A French-Swiss Collaboration

Conditions
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Obesity, Childhood

Intervention / Treatment
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* Drug: Monthly bolus of cholecalciferol per os
* Drug: Daily dose of cholecalciferol per os
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 5 to 18 year-old Being obese (BMI >97th percentile for age and gender using the WHO references) Patients (parents) having given their informed consent Patient having insurance from the national health system Exclusion Criteria: Children will be excluded from the study if: They suffer from symptomatic vitamin D deficiency (tetany, muscular hypotonia, hypocalcaemic seizure) or present signs of rickets at the X-ray (osteopenia and cortical thinning of the long bones, stress fractures, and metaphyseal widening and fraying. The earliest rachitic change is a loss of demarcation between the metaphysic and growth plate and loss of the provisional zone of calcification). A 10-point radiographic scoring system will be used to assess the presence and the severity of rickets on the basis of knee and wrist findings. They suffer from a chronic disease such as granulomatous conditions, Williams syndrome, or hypothyroidism predisposing to hypocalcaemia or in case of hypercalcaemia, liver/kidney disease, malabsorption diseases. They are under treatment of anticonvulsivants/barbiturates or steroids which increase the catabolism of 25(OH)D. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product. Pregnancy. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant. Previous enrolment into the current study

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monthly bolus arm<br> | Drug: Monthly bolus of cholecalciferol per os<br>* Bolus therapy (100'000 - 200'000 IU/month depending on age: < or ≥ 9 years old) for 3 months<br>|
| Active Comparator: Daily arm<br> | Drug: Daily dose of cholecalciferol per os<br>* Daily substitution (3'500 to 6'500 IU/day depending on age: < or ≥ 9 years old) for 3 months<br>|
| Other: Control group<br>Group of obese patients without vitamin D deficiency | Other: Control<br>* no cholecalciferol therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients reaching the therapeutic target defined as vitamin D (25(OH)D) serum level ≥ 50 nmol/L and < 120 nmol/L |  | Month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| calcium dosages | blood safety dosages | Month 4 | 
| phosphore dosages | blood safety dosages | Month 4 | 
| urinary calcium | urinary safety dosages | Month 4 | 
| creatinin | urinary safety dosages | Month 4 | 
| Treatment compliance |  | Month 4 | 
| Evaluation of influence of type of skin on study results | assessed by Fitzpatrick scale | Month 4 | 
| Evaluation of influence of sun exposure on study results | assessed by a questionnaire | Month 4 | 
| Evaluation of influence of physical activity on study results | assessed by a questionnaire | Month 4 | 
| Evaluation of influence of alimentary intakes on study results | assessed by questionnaires | Month 4 | 
| Modeling of vitamin D concentration | Modeling and simulation of vitamin D concentration in obese children and adolescents using a mathematical PBPK model | Month 4 | 
| Evaluation of one mineral density by biphotonic absorptiometry in the spine | Comparison of the both treated arms with the control group | Day 1 | 
| Evaluation of one mineral density by biphotonic absorptiometry in the femoral neck | Comparison of the both treated arms with the control group | Day 1 | 
| Evaluation of bone micro-architecture (HRpQCT) at the radius | Comparison of the both treated arms with the control group | Day 1 | 
| Evaluation of bone micro-architecture (HRpQCT) at the tibia | Comparison of the both treated arms with the control group | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Vitamin D deficiency,, supplementation,, Child, Adolescent