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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Obesity

Intervention / Treatment
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* Drug: Vitamin D supplementation
* Drug: Placebo
* Other: 3 months lifestyle and dietary management
* Other: Normal control


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Non-Obese group<br>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<br>* Patients in this group do not have experimental intervention in order to provide measures of a real-life control group.<br>|
| Experimental: Obese group, Vitamin D<br>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<br>* Patients randomized to this group will receive 4000 UI of Vitamin D3 per day for 90 days.<br>Other: 3 months lifestyle and dietary management<br>* 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.<br>|
| Placebo Comparator: Obese group, placebo<br>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 | Drug: Placebo<br>* Patients randomized to this group will receive placebo for 90 days.<br>Other: 3 months lifestyle and dietary management<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |