Clinical trial NCT01797302: Vitamin D and Vascular Health in Children
Official title: Vitamin D and Vascular Function in Obese Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Vitamin D Deficiency
Keywords: Obesity
Vitamin D Deficiency
Vascular Function
Insulin resistance
metabolic syndrome
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Office of Dietary Supplements (ODS)
First posted: 2013-02-22
Enrollment: 225
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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.

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.

Primary outcomes:
measure: Flow-mediated Dilation (FMD) Percentage
timeFrame: 6 months
Secondary outcomes:
measure: Pulse-wave Velocity (PWV)
timeFrame: 6 months
measure: Augmentation Index at Heart Rate of 75 Beats/Min (AIx-75)
timeFrame: 6 months
measure: Central Systolic Blood Pressure
timeFrame: 6 months
measure: Central Diastolic Blood Pressure
timeFrame: 6 months
measure: Systemic Systolic Blood Pressure
timeFrame: 6 months
measure: Systemic Diastolic Blood Pressure
timeFrame: 6 months
measure: Fasting Blood Glucose
timeFrame: 6 months
measure: 1/Fasting Insulin Ratio
timeFrame: 6 months
Other outcomes:
measure: Body Mass Index (BMI)
timeFrame: 6 months
Locations:
city: Pittsburgh
country: United States
facility: Primary Care Center, Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh, Children's Hospital of Pittsburgh of UPMC
name: Kumaravel Rajakumar, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rajakumar K, Moore CG, Khalid AT, Vallejo AN, Virji MA, Holick MF, Greenspan SL, Arslanian S, Reis SE. Effect of vitamin D3 supplementation on vascular and metabolic health of vitamin D-deficient overweight and obese children: a randomized clinical trial. Am J Clin Nutr. 2020 Apr 1;111(4):757-768. doi: 10.1093/ajcn/nqz340.