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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03516968

Collaborator

(none)

156

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Obesity, Childhood	Drug: Monthly bolus of cholecalciferol per os Drug: Daily dose of cholecalciferol per os Other: Control	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

156 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2026

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Monthly bolus arm

Drug: Monthly bolus of cholecalciferol per os

Bolus therapy (100'000 - 200'000 IU/month depending on age: < or ≥ 9 years old) for 3 months

Active Comparator: Daily arm

Drug: Daily dose of cholecalciferol per os

Daily substitution (3'500 to 6'500 IU/day depending on age: < or ≥ 9 years old) for 3 months

Other: Control group

Group of obese patients without vitamin D deficiency

Other: Control

no cholecalciferol therapy

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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