Effects of Vitamin D Dose and Genotype of the Binding Protein in Infants and Children

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if the vitamin D binding protein genotype influences circulating vitamin D levels and if it may have functional consequences on vitamin D activity.

Detailed Description
-----------------
Vitamin D has recently been the subject of much attention. Advantages to the prevention of vitamin D deficiency (VDD) in young children are obvious: acutely, hypocalcemic seizures may occur in VDD, and rickets can result in long-term skeletal deformities. Previous research has emphasized the importance of identifying optimal supplementation doses and appropriate target thresholds for circulating 25-hydroxyvitamin D (25-OHD), the best described marker of vitamin D status. The timely next step is to objectively establish effective doses for the prevention of VDD, without creating risk from overzealous supplementation, in a population representative of those most at risk for overt disease. Although the primary role of vitamin D is considered to be its effect on intestinal calcium absorption, enormous variability of fractional calcium absorption in relation to 25-OHD levels exists. We provide evidence that a significant component of this variability is genetic in nature and in particular, relates to vitamin D binding protein (DBP) genotype. The aggregate data suggest that the critical mechanism for the development of nutritional rickets is reduction in availability of calcium to the skeleton, which is largely determined by vitamin D status and intestinal calcium absorption. Our proposal focuses on the establishment of a workable definition of vitamin D deficiency in an underserved and highly vulnerable population and to assess the impact of genetic variance in VDR and DBP as factors to be considered in the recommendation of vitamin D status assessment, taking into account the outcome of 25-OHD level, and in additional studies, potential functional consequences of vitamin D related to both its classical and non-classical effects.

Official Title
-----------------
A Randomized, Controlled Trial of Vitamin D Supplementation in Infants and Children: Effects of Vitamin D Dose and Genotype of the Binding Protein

Conditions
-----------------
Vitamin D Deficiency

Intervention / Treatment
-----------------
* Dietary Supplement: Vitamin D


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 6 months to 6 years of age healthy or free from any diseases or conditions that may affect nutritional status or bone metabolism willingness of family to participate in a 6-month study of vitamin D supplementation Exclusion Criteria: Chronic disease Prematurity < 32 weeks gestational age Liver disease such as hepatitis or renal/urologic disease (e.g., recurrent urinary tract infection) Use of pharmacologic or prescription-level dosages of vitamin D or its metabolites. We will exclude users of any systemic glucocorticoid preparation and users of inhaled steroids that are considered greater than medium dose for age 4 yrs. Specifically, this would exclude users of over 1 mg/day of budesonide, and over 352 mcg/day of fluticasone. Current or recent (within 1 month) use of anticonvulsants or other medications known to affect bone and mineral homeostasis or alkaline phosphatase levels.

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: Vitamin D|Vitamin D (either 400 IU vs 1000 IU) given orally each day|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in serum 25-OH vitamin D |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vitamin D Deficiency, VDD, Vitamin D Supplementation, Vitamin D Binding Protein, DBP, Nutritional rickets, rickets, 25hydroxyvitamin D, 25OHD, 1,25OH2D, vitamin D metabolites, PTH, vitamin D homeostasis