Vitamin D and Vascular Health in Children

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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) Waist Circumference Serum High Density Lipoprotein (HDL) Cholesterol Serum Triglycerides Inflammatory markers (Plasma TNF-alpha, high-sensitivity C-reactive protein, and IL-6) Adiopkines (Plasma Leptin and Adiponectin) Plasma nitric oxide metabolites were not measured.

Official Title
-----------------
Vitamin D and Vascular Function in Obese Children

Conditions
-----------------
Obesity, Vitamin D Deficiency

Intervention / Treatment
-----------------
* Dietary Supplement: Vitamin D3


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 10 Years
Maximum Age: 18 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D3 2000 IU<br>Vitamin D3 2000 IU tablet once daily by mouth for 6 months | Dietary Supplement: Vitamin D3<br>* Tablet form<br>* Other names: Cholecalciferol;|
| Active Comparator: Vitamin D3 1000 IU<br>Vitamin D3 1000 IU tablet by mouth once daily for 6 months | Dietary Supplement: Vitamin D3<br>* Tablet form<br>* Other names: Cholecalciferol;|
| Placebo Comparator: Vitamin D3 600 IU<br>Vitamin D3 600 IU tablet by mouth once daily for 6 months | Dietary Supplement: Vitamin D3<br>* Tablet form<br>* Other names: Cholecalciferol;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulse-wave Velocity (PWV) | PWV is a measure of arterial stiffness. Higher values of PWV indicate greater degree of arterial stiffness. | 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. | 6 months | 
| Central Systolic Blood Pressure | a measure of cardiometabolic health | 6 months | 
| Central Diastolic Blood Pressure | a measure of cardiometabolic health | 6 months | 
| Systemic Systolic Blood Pressure | a measure of cardiometabolic health | 6 months | 
| Systemic Diastolic Blood Pressure | a measure of cardiometabolic health | 6 months | 
| Fasting Blood Glucose | a measure of cardiometabolic health | 6 months | 
| 1/Fasting Insulin Ratio | 1/fasting insulin ratio is a measure of insulin sensitivity. Increases in 1/fasting insulin ratio indicate improvements in insulin sensitivity. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Obesity, Vitamin D Deficiency, Vascular Function, Insulin resistance, metabolic syndrome