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

Официальное название

Treatment of Vitamin D Deficit in Obese Children and Adolescents: an Open Label Randomized Controlled Study Comparing the Efficacy of Two Oral Supplementation Regimens: Monthly Boluses Versus Daily Doses for Correcting Blood Vitamin D Level: OBEVIDOS

Обзор

Childhood obesity is one of the most serious public health challenges of the 21st century, with an increasing prevalence over time in developed countries. Overweight and obese children and adolescents are likely to remain so into adulthood and to develop chronic diseases at a young age, such as diabetes and cardiovascular disease. Obese patients, whether adults or children, are likely to have low serum vitamin D levels due to sequestration and/or volumetric dilution of this fat-soluble vitamin in adipose tissue. Studies have established a link between vitamin D deficiency or insufficiency and chronic diseases such as hypertension, type 2 diabetes and other metabolic problems. Determining physiological 25(OH)D levels to ensure optimal phosphocalcic metabolism and bone mineralisation requires the use of functional markers: parathyroid hormone (PTH) levels, assessment of the intestinal calcium absorption fraction, assessment of bone mineral density and bone mineral content using absorptiometry. Vitamin D deficiency leads to malabsorption of calcium and phosphate in the digestive tract, with concentrations, especially of calcium, tending to fall in plasma, resulting in hypersecretion of PTH, which mobilises bone calcium to maintain subnormal blood calcium levels. Each unit increase in BMI is associated with lower serum vitamin D concentrations: given these low concentrations in this population associated with the risk of developing pathologies, it is important to ensure adequate vitamin D supplementation. The latest paediatric recommendations recommend, for children aged between 1 and 18 with vitamin D deficiency, a supplement of 2,000 IU/day for at least 6 weeks or a bolus of 50,000 IU once a week for at least 6 weeks. There are different dosage regimens for the replacement of vitamin D deficiency depending on the country: there is a lack of data on the appropriate dosage and administration regimens for vitamin D supplementation in cases of deficiency, particularly in obese children and adolescents. A prospective, randomised clinical trial will make it possible to define the vitamin D supplementation regimen best suited to increasing serum vitamin D levels in these children and adolescents suffering from obesity.

Вмешательства

• Препарат Monthly bolus of cholecalciferol per os
  Bolus therapy: first 50 000 IU and a second 50 IU after 6 weeks
• Препарат Daily dose of cholecalciferol per os
  Daily substitution, 1200 IU per day (4 drops), for 3 months

Первичные конечные точки

• Proportion of patients reaching the therapeutic target defined as vitamin D (25(OH)D) serum level ≥ 50 nmol/L and < 120 nmol/L [Срок оценки: Month 3]

Вторичные конечные точки (12)

• calcium dosages [Срок оценки: Month 3]
• phosphore dosages [Срок оценки: Month 3]
• vitamin D (25(OH)D) dosages [Срок оценки: Month 3]
• urinary calcium [Срок оценки: Month 3]
• creatinin [Срок оценки: Month 3]
• Treatment compliance [Срок оценки: Month 3]
• Evaluation of influence of type of skin on study results [Срок оценки: Month 3]
• Evaluation of influence of physical activity on study results [Срок оценки: Month 3]
• Evaluation of influence of sun exposure on study results [Срок оценки: Month 3]
• Evaluation of influence of alimentary intakes on study results [Срок оценки: Month 3]
• Bone mineral density description (DXA) [Срок оценки: Day 1]
• Evaluation of the PTH variation [Срок оценки: Month 3]

Критерии участия

Критерии включения

• Aged between 5 to 18 year-old
• Being obese (BMI >97th percentile, > IOTF 30, for age and gender using the WHO references)
• Patients (parents) having given their informed consent
• Patient having insurance from the national health system

Критерии исключения

Children will be excluded from the study if:

• Symptomatic vitamin D deficiency (tetany, muscular hypotonia, hypocalcaemic seizure)
• Vitamin D supplementation in the 3 months preceding the inclusion visit (V1)
• Signs of rickets at the X-ray (osteopenia and cortical thinning of the long bones, stress fractures, and metaphyseal widening and fraying)
• Chronic disease such as granulomatous conditions, Williams syndrome, or hypothyroidism predisposing to hypocalcaemia or in case of hypercalcaemia (calcium > 2.65 mmol/L), liver/kidney disease, malabsorption diseases;
• Hypercalciuria (urinary Calcium/Creatinine > 0.7 mmol/mmol), calcium nephrolithiasis, hypervitaminosis D (25-(OH)D > 250 nmol/L); nephrocalcinosis;
• Ongoing treatment with anticonvulsants/barbiturates or steroids which increase the catabolism of 25(OH)D;
• Ongoing treatment with thiazides diuretics which reduce urinary excretion of calcium;
• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product;
• Pregnancy, breastfeeding;
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant;
• Simultaneous enrolment to another study which could influence the results of the current study;
• Patient under legal protection or deprived of liberty.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 4 центра

• Centre d'Investigation Clinique de LYON - CIC 1407- Groupement Hospitalier Est / Hospices — Bron
• Service d'endocrinologie et métabolisme pédiatrique, Hôpital Femme Mère Enfant — Bron
• Service d'Endocrinologie Pédiatrique CHU de Clermont-Ferrand — Clermont-Ferrand
• Centre Médical Infantile de Romagnat — Romagnat

Идентификаторы

NCT: NCT03516968 · 69HCL18_0148

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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