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

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 b...

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Autores principales: Pastor-Villaescusa, Belén, Caballero-Villarraso, Javier, Cañete, M. Dolores, Hoyos, Raúl, Maldonado, José, Bueno, Gloria, Leis, Rosaura, Gil, Ángel, Cañete, Ramón, Aguilera, Concepción M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950074/
https://www.ncbi.nlm.nih.gov/pubmed/27432166
http://dx.doi.org/10.1186/s13063-016-1403-4
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author Pastor-Villaescusa, Belén
Caballero-Villarraso, Javier
Cañete, M. Dolores
Hoyos, Raúl
Maldonado, José
Bueno, Gloria
Leis, Rosaura
Gil, Ángel
Cañete, Ramón
Aguilera, Concepción M.
author_facet Pastor-Villaescusa, Belén
Caballero-Villarraso, Javier
Cañete, M. Dolores
Hoyos, Raúl
Maldonado, José
Bueno, Gloria
Leis, Rosaura
Gil, Ángel
Cañete, Ramón
Aguilera, Concepción M.
author_sort Pastor-Villaescusa, Belén
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1403-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-49500742016-07-20 Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial Pastor-Villaescusa, Belén Caballero-Villarraso, Javier Cañete, M. Dolores Hoyos, Raúl Maldonado, José Bueno, Gloria Leis, Rosaura Gil, Ángel Cañete, Ramón Aguilera, Concepción M. Trials Study Protocol 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1403-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-18 /pmc/articles/PMC4950074/ /pubmed/27432166 http://dx.doi.org/10.1186/s13063-016-1403-4 Text en © Pastor-Villaescusa et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Study Protocol
Pastor-Villaescusa, Belén
Caballero-Villarraso, Javier
Cañete, M. Dolores
Hoyos, Raúl
Maldonado, José
Bueno, Gloria
Leis, Rosaura
Gil, Ángel
Cañete, Ramón
Aguilera, Concepción M.
Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial
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
title_full Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial
title_fullStr Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial
title_full_unstemmed Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial
title_short Evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial
title_sort evaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: study protocol for a randomized controlled trial
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950074/
https://www.ncbi.nlm.nih.gov/pubmed/27432166
http://dx.doi.org/10.1186/s13063-016-1403-4
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