000056750 001__ 56750 000056750 005__ 20220525082802.0 000056750 0247_ $$2doi$$a10.1186/s13063-016-1403-4 000056750 0248_ $$2sideral$$a96066 000056750 037__ $$aART-2016-96066 000056750 041__ $$aeng 000056750 100__ $$aPastor-Villaescusa, B. 000056750 245__ $$aEvaluation of differential effects of metformin treatment in obese children according to pubertal stage and genetic variations: Study protocol for a randomized controlled trial 000056750 260__ $$c2016 000056750 5060_ $$aAccess copy available to the general public$$fUnrestricted 000056750 5203_ $$aBackground: 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. 000056750 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000056750 590__ $$a1.969$$b2016 000056750 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b78 / 128 = 0.609$$c2016$$dQ3$$eT2 000056750 592__ $$a1.24$$b2016 000056750 593__ $$aPharmacology (medical)$$c2016$$dQ1 000056750 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1 000056750 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000056750 700__ $$aCaballero-Villarraso, J. 000056750 700__ $$aCañete, M.D. 000056750 700__ $$aHoyos, R. 000056750 700__ $$aMaldonado, J. 000056750 700__ $$0(orcid)0000-0002-0902-387X$$aBueno, G.$$uUniversidad de Zaragoza 000056750 700__ $$aLeis, R. 000056750 700__ $$aGil, Á. 000056750 700__ $$aCañete, R. 000056750 700__ $$aAguilera, C.M. 000056750 7102_ $$11010$$2670$$aUniversidad de Zaragoza$$bDpto. Pediatría Radiol.Med.Fís$$cÁrea Pediatría 000056750 773__ $$g17, 1 (2016), 323 [10 pp.]$$pTrials$$tTrials$$x1745-6215 000056750 8564_ $$s666067$$uhttps://zaguan.unizar.es/record/56750/files/texto_completo.pdf$$yVersión publicada 000056750 8564_ $$s87906$$uhttps://zaguan.unizar.es/record/56750/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000056750 909CO $$ooai:zaguan.unizar.es:56750$$particulos$$pdriver 000056750 951__ $$a2022-05-25-08:23:58 000056750 980__ $$aARTICLE