Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.

Study Overview
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Brief Summary
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Vitamin D is not seen anymore only as a phosphocalcic and bone hormone, but also as having an effect on global health (anti-infective, anti-inflammatory, anti-tumour roles and cardiovascular protection). Until recently, vitamin D repletion was defined as the minimal concentration that enables the prevention of rickets in children and osteomalacia in adults, i.e, approximately 8 ng/mL (20 nmol/L). However, most of the international experts agree to set minimal threshold of 25 OH vitamin D serum concentration, higher than the one previously admitted, with a limit of 20 ng/mL (50 nmol/L) to define a vitamin D deficiency and a limit of 30 ng/mL (75 nmol/L) to define vitamin D insufficiency. Recommendations for Vit D supplementation in healthy children were updated in France in 2012. The invariable supplementation of infants and toddlers is efficient since deficiency-related rickets have almost disappeared; however there is very few information in ill children populations. Vit D supplementation tolerance is usually considered as good and over-dosage risks are low, however these studies were conducted more than 30 years ago, and as far as we know, there is no study about calcium urinary excretion kinetics after intake of a 100 000 IU vial of cholecalciferol (Uvedose®). When 25 OH vitamin D serum concentrations exceeds 200 ng/mL, which is very rare in daily practice, toxic effects of Vit D may theoretically be observed, particularly hypercalcemia and hypercalciuria. Vitamin D deficit is very common in children with chronic kidney disease (CKD) with a 50 to 92% prevalence depending on the studies; it it is a risk factor for secondary hyperparathyroidism. Although international guidelines regarding the care of CKD children recommend 25 OH vitamin D serum concentrations over 75 nmol/L, there are no practical recommendations in terms of dose and frequency of native Vit D treatment. Therefore, the objectives of the present study has are the following: to validate prospectively the efficacy of our service usual care for Vit D supplementation of children and adolescents seen in the paediatric nephrology department. and to study the effect of Vit D supplementation (100 000 IU vial of cholecalciferol) on calciuria in these patients.

Official Title
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Vitamin D Supplementation in Children and Adolescents Seen in the Paediatric Nephrology Service: Study of the Efficacy of Service Usual Care (Cholecalciferol) and Its Impact on Calciuria.

Conditions
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Chronic Kidney Disease, Renal Transplantation, Nephrotic Syndrome

Intervention / Treatment
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* Drug: Cholecalciferol vial (100 000 UI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age : between [18 mo et 18 yo[ Patients seen in the paediatric nephrology service and having : Chronic kidney disease Renal transplant Stable nephrotic syndrome (i.e., normal protidemia at inclusion) Initial 25 OH vitamin D concentration < 75nmol/l Patient agree to participate (if old enough to give his agreement) and written informed consent signed by parents Patients affiliated within the French universal healthcare system Exclusion Criteria: - Contraindication to 100 000 IU Uvedose® treatment (according to the Summary of Product Characteristics: known hypersensitivity to vitamin D or hypercalcemia, hypercalciuria or nephrolithiasis).

Ages Eligible for Study
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Minimum Age: 18 Months
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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Usual vitamin D supplementation<br> | Drug: Cholecalciferol vial (100 000 UI)<br>* VISIT 1: Patient > 60 kg and initial 25OHD serum concentration < 25nmol/L : prescription of 4 vials to be taken every 2 weeks between 25 and 50 nmol/L: prescription of 3 vials to be taken every 2 weeks between 50 and 75 nmol/L: prescription of 2 vials to be taken every 2 weeks Patient between 20 and 60 kg and initial 25OHD serum concentration < 25nmol/L: prescription of 2 vials to be taken every month between 25 and 50 nmol/L: prescription of 2 vials to be taken every 6 weeks between 50 and 75 nmol/L: prescription of 1 single vial Patient < 20 kg and initial 25OHD serum concentration < 75 nmol/L: prescription of 1 single vial A local lab will performed urinary dosage of calciuria and creatininuria: at days 0, 1, 2, 3, 4 and 7 after the first intake of a 25OHD vial at days 0, 2 and 4 after other intakes (when applicable) VISIT 2: 25OHD serum concentration will then be dosed at month 2 after visit 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of usual vitamin D supplementation | The 25 OH vitamin D serum concentration will be measured at inclusion (before treatment intake) and 2 months after supplementation. No extra blood intake is programmed since this parameter is always measured in this population. The main evaluation criterion is defined as a 25 OH vitamin D serum concentration over 75 nmol/l at month 2. This defines the success of supplementation. The failure is defined as a 25 OH vitamin D serum concentration under 75 nmol/l at month 2. | Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetics of calciuria after a 100 000 IU vial of cholecalciferol | Calciuria (absolute and normalized with the calculation of the ratio urinary calcium/creatinine) will be measured on the first morning urine at those time points after each vial intake. Measurements will be made in the unique local laboratory chosen by each patient. Thus the lab will be different between patients but must remain the same for each patient. | Day 0, day 1, day 2, day 3, day 4, day 7 after treatment intake. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Calciuria, Paediatrics, Nephrology