Vitamin D and Vascular Health in Children

University of Pittsburgh225 enrolled

Overview

In this study, we will test the central hypothesis that enhancement of vitamin D status in obese and overweight children will improve their vascular health and their cardiovascular disease (CVD) and metabolic syndrome risk profile.

Our primary objective is to determine, in obese and overweight children aged 10 to 18 years with vitamin D deficiency (defined as serum 25-hydroxyvitamin D \<20 ng/mL), the efficacy of enhanced vitamin D3 supplementation in improving vascular endothelial function, arterial stiffness, insulin sensitivity, and metabolic syndrome risk status; and to assess whether these effects are dose-dependent. As a secondary objective, we will examine the vitamin D supplementation-induced effect on adipokines and inflammatory markers relevant to CVD risk. In a double-masked, controlled trial, we will randomize 252 eligible children to receive either 600 IU (conventional supplementation), or 1000 IU or 2000 IU (enhanced supplementation) of vitamin D3 daily for 6 months. In terms of reporting of results, the following pre-specified outcomes are included in the primary manuscript (PubMed PMID:31950134 -- see Reference section for citation details) 1. Waist Circumference 2. Serum High Density Lipoprotein (HDL) Cholesterol 3. Serum Triglycerides 4. Inflammatory markers (Plasma TNF-alpha, high-sensitivity C-reactive protein, and IL-6) 5. Adiopkines (Plasma Leptin and Adiponectin) Plasma nitric oxide metabolites were not measured.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

225

Conditions

Obesity Vitamin D Deficiency

Interventions

Vitamin D3DIETARY_SUPPLEMENT

Tablet form

Eligibility

Sex: ALLMin age: 10 YearsMax age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Eligible subjects will be 10 to 18 years of age; * obese or overweight (BMI ≥85th %tile); * otherwise healthy, and * have a serum 25(OH)D concentration \<20 ng/mL Children taking multivitamins should be able to hold off their multivitamins during the course of the study. Exclusion Criteria: Children will be excluded if they * (a) have hepatic or renal disease, metabolic rickets, malabsorptive disorders, primary hyperparathyroidism, hyperthyroidism, or other chronic disorders that could affect vitamin D metabolism; * (b) are receiving treatment with anticonvulsants, systemic glucocorticoids, pharmacologic doses of vitamin D (≥1000 IU of vitamin D2 or D3 daily), antihypertensives, vasoactive drugs, antilipidemics, metformin, antipsychotics, or other oral insulin regulators; * (c) have cholelithiasis or urolithiasis; * (d) have type 1 or type 2 diabetes; or * (e) have a condition or underlying abnormality that could compromise the safety of the subject. Post-menarchial girls with a positive pregnancy test at randomization, or subjects found during the screening phase to have hypercalcemia (serum calcium \>10.8 mg/dL) or significant fasting hyperglycemia (fasting blood glucose ≥ 125 mg/dL) will also be excluded.

Locations (1)

Primary Care Center, Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Outcomes

Primary Outcomes

Flow-mediated Dilation (FMD) Percentage

Brachial artery flow-mediated dilation percentage is a measure of endothelial function. FMD percentage calculation is based on baseline brachial artery diameter(brachialADbase) and change in brachial artery diameter (brachialADchange) during post-occlusive reactive hyperemia. FMD% was determined using the formula (brachialADchange/brachialADbase) x 100.

Time frame: 6 months

Secondary Outcomes

Pulse-wave Velocity (PWV)

PWV is a measure of arterial stiffness. Higher values of PWV indicate greater degree of arterial stiffness.

Time frame: 6 months

Augmentation Index at Heart Rate of 75 Beats/Min (AIx-75)

AIx-75 is a measure of arterial stiffness. AIx was measured through radial arterial tonometry using SphygmoCor. Radial pulse waveform are analyzed through an automatic software function to determine aortic pulse waveform and aortic or central systolic (cSBP) and diastolic blood pressure (cDBP), and these measurements are further analyzed automatically to calculate AIx. AIx is a composite measure of the magnitude of wave reflection and arterial stiffness in all conduit arteries which affect the timing of the wave reflection. AIx = P2-P1/cSBP-cDBP, where P1 is the height of the incident pressure wave form during systole, P2 is the height of the reflected wave added to the incident wave, cSBP is the aortic systolic BP, and cDBP is the aortic diastolic BP. AIx adjusted to heart rate of 75 beats/min (AIx-75) is a validated index of arterial stiffness, with higher values indicating higher degree of arterial stiffness.

Time frame: 6 months

Central Systolic Blood Pressure

a measure of cardiometabolic health

Time frame: 6 months

Central Diastolic Blood Pressure

a measure of cardiometabolic health

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.