Clinical trial NCT02400151: Vascular and Metabolic Effects of Vitamin D Supplementation Associated With Lifestyle Management in Obese Adolescents
Official title: Vascular and Metabolic Effects of Vitamin D Supplementation Associated With Lifestyle Management in Obese Adolescents: Prospective, Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
Collaborators: name: UMR1260 NORT Nutrition, Obésité et Risque Thrombotique
name: EA4278 PEC Laboratoire de Pharm-Ecologie Cardiovasculaire
First posted: 2015-03-26
Enrollment: 49
Sex: ALL
Minimum age (years): 11
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in Flow Mediated Dilation (%) at the brachial artery
timeFrame: 3 months
Secondary outcomes:
measure: Change from baseline in Nitrate Mediated Dilation (%) at the brachial artery
timeFrame: 3 months
measure: Change from baseline in carotid compliance (mm^2mmHg^-1)
timeFrame: 3 months
measure: Change from baseline in brachial compliance (mm^2mmHg^-1)
timeFrame: 3 months
measure: Change from baseline in arterial wave speed (m*s^-1)
timeFrame: 3 months
measure: Usual Vitamin D intake according to food questionnaire
timeFrame: Baseline
measure: Change from baseline in blood 25(OH)D levels (mmol*L^-1)
timeFrame: 3 months
measure: Change from baseline in blood parathyroid hormone levels (mmol*L^-1)
timeFrame: 3 months
measure: Change from baseline in serum calcium levels (mmol*L^-1)
timeFrame: 3 months
measure: Change from baseline in blood total protein levels (g*L^-1)
timeFrame: 3 months
measure: Change from baseline in Homeostatic model assessment Insulin Resistance
timeFrame: 3 months
measure: Change from baseline in the ratio Low Density Lipoprotein/High Density Lipoprotein
timeFrame: 3 months
measure: Change from baseline in Triglyceride levels
timeFrame: 3 months
measure: Change from baseline in Acetylcholine-Cutaneous Blood Flow peak
timeFrame: 3 months
measure: Change from baseline in Sodium nitroprussiate-Cutaneous Blood Flow peak (%)
timeFrame: 3 months
measure: Change from baseline in Insulin-Cutaneous Blood Flow peak (%)
timeFrame: 3 months
measure: Change from baseline in TNF-alpha (pg*mL^-1)
timeFrame: 3 months
measure: Change from baseline in IL-6 (pg*mL^-1)
timeFrame: 3 months
measure: Change from baseline in High sensitivity C-reactive protein (pg*mL^-1)
timeFrame: 3 months
measure: Change from baseline in leptin (pg*mL^-1)
timeFrame: 3 months
measure: Change from baseline in adiponectin (pg*mL^-1)
timeFrame: 3 months
measure: Change from baseline in SuperOxyde Dismutase (U*gHb^-1)
timeFrame: 3 months
measure: Change from baseline in Isoprostanes (ng*L^-1)
timeFrame: 3 months
measure: Change from baseline in nitrite-nitrate (µmol*L^-1)
timeFrame: 3 months
measure: Change from baseline in PAI-1 (µmol*L^-1)
timeFrame: 3 months
measure: Metabolomic profile
timeFrame: baseline
measure: Metabolomic profile
timeFrame: 3 months
Other outcomes:
Locations:
city: Nîmes Cedex 09
country: France
facility: CHRU de Nîmes - Hôpital Universitaire Carémeau
city: Palavas-Les-Flots
country: France
facility: Institut Saint Pierre
Study officials:
affiliation: Centre Hospitalier Universitaire de Nîmes
name: Antonia Perez Martin, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.