A MULTI-CENTER RAND, PLACEBO CTRL, DBL BLIND TRIAL - METFORMIN IN OBESE ADOLESCE

多中心兰德、安慰剂对照、DBL 盲试验 - 二甲双胍治疗肥胖青少年

• 批准号: 7605856
• 负责人: WILLIAM J KLISH
• 金额: $ 1.38万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605856
• 关键词: Adolescent; Adult; Adverse effects; Americas; Blood Pressure; Body Weight Changes; Body Weight decreased; Body mass index; Body measure procedure; Cardiovascular Diseases; Child; Childhood; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Control Groups; Country; Coupled; Data; Diet; Disease; Drug toxicity; Eating; Effectiveness; End Point; Endocrinologist; Epidemic; Excess Mortality; Fatty acid glycerol esters; Funding; Grant; Hepatic; Hypoglycemic Agents; Individual; Institution; Insulin; Insulin Resistance; Life Style; Metformin; Monitor; Morbidity - disease rate; Nitric Oxide; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Obesity; Oral; Peripheral; Pharmaceutical Preparations; Phase; Placebos; Prevalence; Production; Publishing; Purpose; Rate; Research; Research Personnel; Resources; Risk; Safety; Source; Testing; Therapeutic; Time; United States Department of Veterans Affairs; United States Food and Drug Administration; United States National Institutes of Health; Weight; Weight Gain; Youth; abstracting; blind; design; diabetic; follow-up; gastrointestinal; glucophage; glucose production; improved; insulin secretion; insulin sensitivity; lifestyle intervention; male; mortality; non-diabetic; obesity treatment; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ABSTRACT I. HYPOTHESIS This trial will test the hypothesis that among obese adolescents, treatment with extended-release metformin (Glucophage XR), coupled with a lifestyle intervention, will result in decreased obesity (as measured by Body Mass Index [BMI]) II SPECIFIC AIMS The purpose of this study is to determine the safety and effectiveness of metformin XR in treating obesity. The primary study endpoint is change in BMI. Drug toxicity and side effects will be monitored. Since there is no proven effective and lasting treatment for obesity, a disease that is associated with morbidity and mortality, metformin XR is a reasonable therapeutic option. III. BACKGROUND AND SIGNIFICANCE America is facing an epidemic of obesity among its youth. In the last seven years, there has been a 50% increase in the prevalence of obesity as defined by a Body Mass Index (BMI) > 30 kg/m[3, 4]. For the morbidly obese adult, which is defined as having a BMI > 35 kg/m, mortality is increased by 152 to 279% [5]. In a Veterans Administration study of obese 25-34 year old males, there was a 13-fold excess mortality rate over 7 years [6]. As in adults, risks associated with childhood and adolescent obesity include elevated blood pressure and cholesterol levels, predisposing these individuals to cardiovascular disease. In addition, a significant number of obese youth have abnormally high concentrations of insulin, with an attendant increased risk of developing type 2 diabetes mellitus. Currently, limited options are available to help such individuals. While attempts at lifestyle change (e.g., altering diet and activity level) may have some success in the short term, attempts at maintaining weight loss over the long term often fail. Furthermore, there are no current medications that will safely induce significant weight loss over time. Metformin Metformin is an oral antihyperglycemic, insulin-sensitizing agent that has been used in many countries for treatment of type 2 diabetes for more than 40 years. In March 1995, it was approved by the Food and Drug Administration for the treatment of adult type 2 diabetes. Metformin improves insulin sensitivity and reduces insulin resistance by hepatic and peripheral actions. It does not increase insulin secretion [7-11]. Further, metformin decreases hepatic glucose production and results in weight loss [12]. Compared to available drugs that act similarly, only metformin has weight-lowering activity, perhaps by increasing nitric oxide production and improving insulin sensitivity [13]. It is also possible that the mild gastrointestinal side effects of metformin induce weight loss. Metformin is therefore often the agent of choice in obese, type 2 diabetics [14]. In a study of non-diabetic obese adults, treatment with metformin resulted in decreased food intake, and decreased body weight and fat [15]. Metformin is commonly used in adolescent type 2 diabetics and has a good safety record, even following inadvertent administration to children [16]. Although many pediatric endocrinologists treat obese adolescents and those with high insulin levels with metformin, there are only limited published data to support this therapeutic course. For this reason, this study was designed to determine whether metformin XR is safe and effective in treating obese non-diabetic adolescents. In addition, there is very little information about how one's weight changes once treatment with metformin is discontinued. In this study, the one year Follow-up phase will allow for a determination of whether metformin XR continues to be effective once it is discontinued. Conversely, data collected during the Follow-up phase will be analyzed in order to assess whether there is a deleterious effect on a subject"s weight once metformin XR is discontinued (e.g., whether there will be increased weight gain among the subjects in the Metformin group during the Follow-up phase as compared to the subjects in the Control group).

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 摘要 I. 假设 本试验将检验以下假设：在肥胖青少年中，二甲双胍缓释剂（格华止XR）治疗结合生活方式干预将导致肥胖减少（通过体重指数[BMI]测量） II 具体目标 本研究的目的是确定二甲双胍XR治疗肥胖的安全性和有效性。主要研究终点是BMI的变化。将监测药物毒性和副作用。由于目前尚无有效且持久的治疗肥胖症的方法，这种疾病与发病率和死亡率相关，因此二甲双胍XR是一种合理的治疗选择。 三. 背景和意义 美国正面临着年轻人肥胖的流行。在过去的七年中，肥胖症的患病率增加了50%，定义为体重指数（BMI）> 30 kg/m[3，4]。对于定义为BMI > 35 kg/m2的病态肥胖成人，死亡率增加152 - 279% [5]。在退伍军人管理局对25-34岁肥胖男性的一项研究中，7年内的死亡率高出13倍[6]。与成人一样，与儿童和青少年肥胖相关的风险包括血压和胆固醇水平升高，使这些人易患心血管疾病。此外，大量肥胖青年的胰岛素浓度异常高，随之而来的是患2型糖尿病的风险增加。目前，帮助此类个人的选择有限。虽然尝试改变生活方式（例如，改变饮食和活动水平）可能会在短期内取得一些成功，但长期维持减肥的尝试往往会失败。此外，目前还没有药物可以安全地随着时间的推移引起显著的体重减轻。二甲双胍二甲双胍是一种口服降糖药，胰岛素增敏剂，已在许多国家用于治疗2型糖尿病超过40年。1995年3月，它被美国食品和药物管理局批准用于治疗成人2型糖尿病。二甲双胍通过肝脏和外周作用改善胰岛素敏感性并降低胰岛素抵抗。它不会增加胰岛素分泌[7-11]。此外，二甲双胍可降低肝葡萄糖生成并导致体重减轻[12]。与具有类似作用的现有药物相比，只有二甲双胍具有减肥活性，可能是通过增加一氧化氮的产生和改善胰岛素敏感性[13]。二甲双胍的轻度胃肠道副作用也可能导致体重减轻。因此，二甲双胍通常是肥胖2型糖尿病患者的首选药物[14]。在一项非糖尿病肥胖成人研究中，二甲双胍治疗导致摄食量减少，体重和脂肪减少[15]。二甲双胍常用于青少年2型糖尿病患者，即使在儿童意外给药后也具有良好的安全性记录[16]。虽然许多儿科内分泌学家用二甲双胍治疗肥胖青少年和胰岛素水平高的青少年，但只有有限的已发表数据支持这种治疗过程。因此，本研究旨在确定二甲双胍XR治疗肥胖非糖尿病青少年是否安全有效。此外，关于二甲双胍停药后体重变化的信息很少。在本研究中，1年随访期将允许确定二甲双胍XR在停药后是否继续有效。相反，将对随访期收集的数据进行分析，以评估二甲双胍XR停药后是否对受试者的体重产生有害影响（例如，与对照组中的受试者相比，在随访期期间，Metabolic组中的受试者的体重增加是否增加）。