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

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.

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Nephrotic Syndrome; Renal Transplantation
• Intervention / Treatment: Drug: Cholecalciferol vial (100 000 UI)

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Bron, France, 69500
    • Centre de Référence des Maladies Rénales Rares - Hospices Civils de Lyon - Service de Néphrologie et Rhumatologie Pédiatriques - Hôpital Femme Mère Enfant

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Usual vitamin D supplementation

Drug: Cholecalciferol vial (100 000 UI); 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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Justine Bacchetta, MD, HCL

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: September 10, 2014
• First Submitted That Met QC Criteria: September 10, 2014
• First Posted (Estimate): September 12, 2014

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Vitamin D, Calciuria, Paediatrics, Nephrology
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Nephrotic Syndrome; Nephrosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 2013-812; 2013-002710-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO