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

Yale University

Status

Completed

Conditions

Vitamin D Deficiency

Treatments

Dietary Supplement: Vitamin D

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01050387

1RC1HD063562 (U.S. NIH Grant/Contract)

M#136410

0909005699

Details and patient eligibility

About

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.

Full 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.

Enrollment

193 patients

Sex

All

Ages

6 months to 6 years old

Volunteers

Accepts Healthy Volunteers

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.