Pastor-Villaescusa Belén, Caballero-Villarraso Javier, Cañete M Dolores, Hoyos Raúl, Maldonado José, Bueno Gloria, Leis Rosaura, Gil Ángel, Cañete Ramón, Aguilera Concepción M
Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Center of Biomedical Research Laboratory 123, University of Granada, Avenida del Conocimiento s/n. 18006 Armilla, Granada, Spain.
Clinical Analysis Services. IMIBIC/Reina Sofía Hospital, Córdoba University, Córdoba, Spain.
Trials. 2016 Jul 18;17(1):323. doi: 10.1186/s13063-016-1403-4.
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.
This study will assess the differential response of metformin treatment at six months in pre-pubertal and pubertal obese children.
Registered by European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011.
超重和肥胖被视为严重的公共卫生问题。在儿科人群中，与肥胖相关的胰岛素抵抗、血脂异常和高血压的发生率不断增加。二甲双胍是一种口服抗高血糖药物，已被证明对治疗糖尿病和非糖尿病肥胖成年人有效。大量的药物遗传学研究表明，基因变异是影响二甲双胍疗效的主要因素之一。此外，最近还描述了二甲双胍作用的潜在微生物群介导机制。然而，针对儿童的相关研究很少，且未关注青春期发育的潜在影响。因此，本研究的主要目的是在一项随机对照试验（RCT）中，根据青春期阶段、基因变异和肠道微生物群特征，评估二甲双胍治疗联合生活方式建议对肥胖儿童的影响。
方法/设计：这是一项随机、前瞻性、双盲、安慰剂对照、多中心试验，按青春期和性别分层。西班牙的四家临床医院正在招募80名青春期前（40名男孩和40名女孩）和80名青春期非糖尿病肥胖儿童（40名男孩和40名女孩）。参与RCT的纳入标准包括体重指数（BMI）高于第95百分位数且年龄在7至14岁之间。青春期阶段根据坦纳标准确定。参与者根据随机分组方案分为两组，两组均接受1克二甲双胍或安慰剂治疗六个月，并结合健康的生活方式建议。主要结局包括BMI Z评分的变化以及与胰岛素抵抗综合征早期出现、炎症、心血管风险相关的生物标志物，这些指标取决于二甲双胍反应的基因决定因素，以及微生物群的可能变化。
本研究将评估青春期前和青春期肥胖儿童在六个月时二甲双胍治疗的差异反应。
于2011年11月14日由欧洲临床试验数据库（EudraCT，ID：2010 - 023061 - 21）注册。
