Vascular and Metabolic Effects of Vitamin D Supplementation Associated With Lifestyle Management in Obese Adolescents (VIDADO)

Vascular and Metabolic Effects of Vitamin D Supplementation Associated With Lifestyle Management in Obese Adolescents: Prospective, Randomized, Controlled Trial

The main objective of this study is to analyze in a population of obese adolescents, the effect of vitamin D3 supplementation in addition to lifestyle and dietary management on vascular function assessed by the change between M0 and M3 of endothelium-dependent vasorelaxation measured at the brachial artery (Flow-Mediated Dilation).

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: Normal control; Drug: Vitamin D supplementation; Other: 3 months lifestyle and dietary management; Drug: Placebo

Detailed Description

The secondary objectives of this study are:

A. To analyze in obese adolescents, the effect of the addition of vitamin D3 supplementation on metabolic and vascular function.

B. To compare the relationships between food intake, metabolic, inflammatory, oxidative stress and vitamin D status, and vascular dysfunction between obese and normal weight subjects.

C. To evaluate the effects of sun exposure variations on relationships described in Objective B by comparing the observed parameters at baseline and at the end of the three month follow-up period, in non-supplemented obese adolescents and adolescents of normal weight.

D. To identify biomarkers (metabolic signatures) in obese adolescents associated with vitamin D deficiency and vascular function.

E. To evaluate in obese adolescents, the effects of vitamin D supplementation on the metabolome (metabolic signature).

F. To evaluate the effects of lifestyle and dietary management on these biomarkers (in the "control group").

For these targets (A to F), all teenagers will be classified according to three levels of skin pigmentation.

G. Establish a biobank of samples taken at baseline and at 3 months.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Nîmes Cedex 09, France, 30029
    • CHRU de Nîmes - Hôpital Universitaire Carémeau
  • Palavas-Les-Flots, France, 34250
    • Institut Saint Pierre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

General Inclusion Criteria:

• The patient's legal representatives must have given their informed and signed consent
• The patient must be insured or beneficiary of a health insurance plan
• Sexual maturation of at least Tanner stage 2

Inclusion criteria for the patient population

• The subject has a body mass index corresponding to grade 2 obesity according to the curves described by Rolland-Cachera et al (1991)
• Absence of at least 5% of total weight over the last 3 months

Inclusion criteria for the control population

• The subject has a body mass index < 90th percentile

Exclusion Criteria:

• The patient is participating in another study
• The patient is in an exclusion period determined by a previous study
• The patient is under judicial protection
• The patient's legal representative(s) refuse(s) to sign the consent
• It is impossible to correctly inform the patient or his/her legal representative(s)
• The patient has a contraindication for physical activity (joint, heart or other)
• The subject does at least 3 hours of extracurricular physical activity per week
• The subject has a concomitant illness, a history of first-degree cardiovascular disease, abnormal glucose tolerance (pre-diabetes or diabetes).
• Active smoking
• Known dyslipidemia (particularly hypercholesterolemia).
• The subject regularly takes food and vitamin supplements and refuses to stop taking these during the study (in case of disruption of these supplements, a wash-out stopping period of 3 weeks is required).
• BMI corresponding to a grade 1 obesity according to the Rolland-Cachera et al. (1991) curves.
• Secondary or known genetic obesity.
• Known hypersensitivity to vitamin D.
• Hypercalcemia, hypercalciuria, calcium lithiasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Non-Obese group; Non-obese patients will be recruited and frequency matched to obese groups according to sex and level of sexual maturation. Intervention: Normal control	Other: Normal control; Patients in this group do not have experimental intervention in order to provide measures of a real-life control group.
Experimental: Obese group, Vitamin D; Subjects randomized to this group will receive vitamin D supplementation. They are recruited from the St Pierre Institute at Palavas-les-Flots, France. Intervention: 3 months lifestyle and dietary management Intervention: Vitamin D supplementation	Drug: Vitamin D supplementation; Patients randomized to this group will receive 4000 UI of Vitamin D3 per day for 90 days.; Other: 3 months lifestyle and dietary management; Lifestyle and dietary management at the Saint Pierre Institute (Palavas-les-Flots, France) occurs for three months. Nutritionally speaking, each child or adolescent receives a controlled and balanced diet, consistent with the recommendations appropriate for his/her age, slightly hypocaloric or normocaloric. This dietary approach is complemented by a nutrition education program and supervision by a doctor and a dietician. Three hours of exercise training per week are scheduled; these sessions include adapted aerobic activities supervised by instructors and educators at the center.
Placebo Comparator: Obese group, placebo; Subjects randomized to this group will receive a placebo supplement. They are recruited from the St Pierre Institute at Palavas-les-Flots, France. Intervention: 3 months lifestyle and dietary management Intervention: Placebo	Other: 3 months lifestyle and dietary management; Lifestyle and dietary management at the Saint Pierre Institute (Palavas-les-Flots, France) occurs for three months. Nutritionally speaking, each child or adolescent receives a controlled and balanced diet, consistent with the recommendations appropriate for his/her age, slightly hypocaloric or normocaloric. This dietary approach is complemented by a nutrition education program and supervision by a doctor and a dietician. Three hours of exercise training per week are scheduled; these sessions include adapted aerobic activities supervised by instructors and educators at the center.; Drug: Placebo; Patients randomized to this group will receive placebo for 90 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Flow Mediated Dilation (%) at the brachial artery	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Nitrate Mediated Dilation (%) at the brachial artery	3 months
Change from baseline in carotid compliance (mm^2mmHg^-1)	3 months
Change from baseline in brachial compliance (mm^2mmHg^-1)	3 months
Change from baseline in arterial wave speed (m*s^-1)	3 months
Usual Vitamin D intake according to food questionnaire	Baseline
Change from baseline in blood 25(OH)D levels (mmol*L^-1)	3 months
Change from baseline in blood parathyroid hormone levels (mmol*L^-1)	3 months
Change from baseline in serum calcium levels (mmol*L^-1)	3 months
Change from baseline in blood total protein levels (g*L^-1)	3 months
Change from baseline in Homeostatic model assessment Insulin Resistance	3 months
Change from baseline in the ratio Low Density Lipoprotein/High Density Lipoprotein	3 months
Change from baseline in Triglyceride levels	3 months
Change from baseline in Acetylcholine-Cutaneous Blood Flow peak	3 months
Change from baseline in Sodium nitroprussiate-Cutaneous Blood Flow peak (%)	3 months
Change from baseline in Insulin-Cutaneous Blood Flow peak (%)	3 months
Change from baseline in TNF-alpha (pg*mL^-1)	3 months
Change from baseline in IL-6 (pg*mL^-1)	3 months
Change from baseline in High sensitivity C-reactive protein (pg*mL^-1)	3 months
Change from baseline in leptin (pg*mL^-1)	3 months
Change from baseline in adiponectin (pg*mL^-1)	3 months
Change from baseline in SuperOxyde Dismutase (U*gHb^-1)	3 months
Change from baseline in Isoprostanes (ng*L^-1)	3 months
Change from baseline in nitrite-nitrate (µmol*L^-1)	3 months
Change from baseline in PAI-1 (µmol*L^-1)	3 months
Metabolomic profile	baseline
Metabolomic profile	3 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Collaborators: UMR1260 NORT Nutrition, Obésité et Risque Thrombotique; EA4278 PEC Laboratoire de Pharm-Ecologie Cardiovasculaire
• Investigators: Study Director: Antonia Perez Martin, MD, PhD, Centre Hospitalier Universitaire de Nîmes

Publications and helpful links

General Publications

• Vinet A, Morrissey C, Perez-Martin A, Goncalves A, Raverdy C, Masson D, Gayrard S, Carrere M, Landrier JF, Amiot MJ. Effect of vitamin D supplementation on microvascular reactivity in obese adolescents: A randomized controlled trial. Nutr Metab Cardiovasc Dis. 2021 Jul 22;31(8):2474-2483. doi: 10.1016/j.numecd.2021.04.025. Epub 2021 May 10.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2015
• Primary Completion (Actual): June 24, 2016
• Study Completion (Actual): June 24, 2016

Study Registration Dates

• First Submitted: March 23, 2015
• First Submitted That Met QC Criteria: March 23, 2015
• First Posted (Estimate): March 26, 2015

Study Record Updates

• Last Update Posted (Actual): June 19, 2017
• Last Update Submitted That Met QC Criteria: June 16, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: LOCAL/2015/APM-01; 2015-000060-34 (EudraCT Number)