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Trials
Published in: Trials 1/2016

Open Access 01-12-2016 | Study protocol

Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial

Authors: Belén Pastor-Villaescusa, Javier Caballero-Villarraso, M. Dolores Cañete, Raúl Hoyos, José Maldonado, Gloria Bueno, Rosaura Leis, Ángel Gil, Ramón Cañete, Concepción M. Aguilera

Published in: Trials | Issue 1/2016

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Abstract

Background

Overweight and obesity are considered to be serious public health problems. In pediatric populations, insulin resistance, dyslipidemia, and hypertension associated with obesity occur with increased frequencies. Metformin is an oral anti-hyperglycemic agent that has been demonstrated to be efficacious in the treatment of diabetic and non-diabetic obese adults. A considerable amount of pharmacogenetic research has demonstrated that genetic variation is one of the major factors affecting metformin response. Additionally, potential microbiota-mediated mechanisms of metformin effect have been recently described. However, scant work has been conducted in children, with no attention being paid to the potential effects of pubertal development. Thus, the main objective of the present study is to evaluate the effect of metformin treatment together with lifestyle recommendations in a randomized control trial (RCT) of obese children according to pubertal stage, genetic variants and signature of gut microbiota.

Methods/design

This is a randomized, prospective, double-blind, placebo-controlled, multicenter trial, which is stratified by puberty and sex. Eighty pre-pubertal (40 boys and 40 girls) and 80 pubertal non-diabetic obese children (40 boys and 40 girls) are being recruited in four Spanish Clinical Hospitals. The inclusion criteria to participate in the RCT include a Body Mass Index (BMI) above the 95th percentile and age 7–14 years. The pubertal stage is determined based on the Tanner criteria. Participants are assigned to two groups in accordance with a randomization schedule and receive 1 g of metformin or placebo for six months in combination with healthy lifestyle recommendations in both groups. The primary outcomes include changes in the BMI Z score and the biomarkers associated with the early appearance of insulin resistance syndrome, inflammation, cardiovascular risk according of the presence of genetic determinants of metformin response, as well as possible modifications in microbiota.

Discussion

This study will assess the differential response of metformin treatment at six months in pre-pubertal and pubertal obese children.

Trial registration

Registered by European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011.
Appendix
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Metadata
Title
Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial
Authors
Belén Pastor-Villaescusa
Javier Caballero-Villarraso
M. Dolores Cañete
Raúl Hoyos
José Maldonado
Gloria Bueno
Rosaura Leis
Ángel Gil
Ramón Cañete
Concepción M. Aguilera
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1403-4

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