Metformin in Obese Children and Adolescents (MetVoorMin)
2017年4月26日 更新者：Van der Vorst、St. Antonius Hospital
An Efficacy, Safety and Pharmacokinetic Study on the Short-term and Long-term Use of Metformin in Obese Children and Adolescents
The purpose of this study is to determine whether metformin is effective in reducing BMI and insulin resistance in obese children and adolescents.
研究概览
详细说明
The prevalence of obesity in children and adolescents is increasing rapidly and is associated with significant medical and psychosocial consequences persisting into adulthood.
Obesity may lead to metabolic complications, such as insulin resistance, which can progress via impaired fasted glucose and impaired glucose tolerance to type 2 diabetes mellitus (T2DM) and to the development of micro- and macro-vascular complications.
Metformin, an oral anti-diabetic licensed for T2DM for adults and children from 10 years onwards, is already used off label in obese children and adolescents with insulin resistance, even though the specific effects of metformin in these obese children and adolescents have not been elucidated, particularly upon long-term use.
The rationale for this study is based on the hypothesis that metformin may reduce body mass index (BMI), insulin resistance and percentage of body-fat in obese children and adolescents with insulin resistance. Further more it is anticipated that metformin may delay the progression to T2DM and thereby micro- and macro-vascular complications in obese children and adolescents with insulin resistance.
研究类型
介入性
注册 (实际的)
62
阶段
- 第三阶段
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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's Hertogenbosch、荷兰
- Jeroen Bosch Hospital
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Nieuwegein、荷兰、3430EM
- St. Antonius Hospital
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
10年 至 16年 (孩子)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Age ≥ 10 and ≤ 16 years at study entry
- Caucasian descent
- Obesity defined as BMI-SDS > 2.3
- Insulin resistance defined as HOMA-IR ≥ 3.4.
- An obtained informed consent from subjects and parents/caregivers.
Exclusion Criteria:
- Presence of T2DM (American Diabetes Association criteria)
- Presence of endocrine disorders with steroid therapy
- Suspicion of polycystic ovarium syndrome;
- Height < -1.3 SD of target height;
- Syndrome disorders with or without mental retardation;
- Use of anti-hyperglycaemic drugs;
- Pregnancy (pregnancy test will be performed, if applicable);
- (History of) alcohol abuse;
- Impaired renal and/or hepatic function (defined as GFR < 80 ml/min. GFR=40 x length (cm) / serumcreatinin (μmol/l and ALAT >150% of normal value for age);
- Use of ritonavir; use of ACE inhibitors;
- Insufficient knowledge of the Dutch language.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器：Metformin
Metformin with lifestyle intervention during 18 months
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Oral administration, 500 mg daily at week 1.
Every week metformin dosage increases with 500 mg, to a maximum dose of 1000 mg bid.
This maximum dose will be administered till the end of the study.
其他名称：
Lifestyle intervention: 18 months physical therapy and dietary advice
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安慰剂比较：Placebo
Placebo and lifestyle intervention during 18 months
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Lifestyle intervention: 18 months physical therapy and dietary advice
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change in BMI from baseline
大体时间：18 months and 36 months
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Change in BMI after part 1 (double blind) and part 2 ( follow-up)
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18 months and 36 months
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Change in Insulin resistance from baseline
大体时间：3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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calculated by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR).
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3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Renal and hepatic function
大体时间：3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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creatinine and alat
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3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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Tolerability
大体时间：3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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The amount of reported adverse effects, in relation to the achieved dose level.
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3; 6; 9; 12; 15; 18; 24; 30 and 36 months
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Pharmacokinetics (PK)-parameters: clearance (ml/min)
大体时间：9 months
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Clearance where applicable expressed per body weight, age category, Tanner Stage and gender, clearance will be determined with a two-compartment pharmacokinetic model using non linear mixed effect modelling.
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9 months
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Body fat percentage
大体时间：0, 9, 18 and 36 months
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0, 9, 18 and 36 months
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Physical fitness
大体时间：0, 9, 18 and 36 months
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0, 9, 18 and 36 months
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Quality of life
大体时间：0, 9, 18 and 36 months
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0, 9, 18 and 36 months
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Long term efficacy
大体时间：36 months
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Based on BMI and HOMA-IR values
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36 months
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Long-term safety
大体时间：36 months
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Renal and hepatic function after 36 months of metformin use
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36 months
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Long-term tolerability
大体时间：36 months
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The amount of adverse effects after 36 months
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36 months
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Microvascular complications
大体时间：36 months
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Measured as micro-albuminuria
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36 months
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Macrovascular complications
大体时间：36 monthts
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Measured with Pulse Wave Velocity and Augmentation Index.
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36 monthts
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Development of T2DM
大体时间：36 months
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36 months
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PK-parameters: volume of distribution (liters)
大体时间：9 months
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Volume of distribution, where applicable expressed per body weight, age category, Tanner Stage and gender, volume of distribution will be determined with a two-compartment pharmacokinetic model using non linear mixed effect modelling.
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9 months
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Marja MJ van der Vorst, MD, PhD、St. Antonius Hospital
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- van Rongen A, van der Aa MP, Matic M, van Schaik RHN, Deneer VHM, van der Vorst MM, Knibbe CAJ. Increased Metformin Clearance in Overweight and Obese Adolescents: A Pharmacokinetic Substudy of a Randomized Controlled Trial. Paediatr Drugs. 2018 Aug;20(4):365-374. doi: 10.1007/s40272-018-0293-1.
- van der Aa MP, Hoving V, van de Garde EM, de Boer A, Knibbe CA, van der Vorst MM. The Effect of Eighteen-Month Metformin Treatment in Obese Adolescents: Comparison of Results Obtained in Daily Practice with Results from a Clinical Trial. J Obes. 2016;2016:7852648. doi: 10.1155/2016/7852648. Epub 2016 Dec 22.
- van der Aa MP, Elst MA, van Mil EG, Knibbe CA, van der Vorst MM. METFORMIN: an efficacy, safety and pharmacokinetic study on the short-term and long-term use in obese children and adolescents - study protocol of a randomized controlled study. Trials. 2014 Jun 5;15:207. doi: 10.1186/1745-6215-15-207.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2011年8月1日
初级完成 (实际的)
2015年8月1日
研究完成 (实际的)
2017年2月28日
研究注册日期
首次提交
2011年10月20日
首先提交符合 QC 标准的
2011年12月6日
首次发布 (估计)
2011年12月8日
研究记录更新
最后更新发布 (实际的)
2017年4月27日
上次提交的符合 QC 标准的更新
2017年4月26日
最后验证
2017年4月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
Metformin的临床试验
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Poznan University of Medical SciencesUniversity of California, San Diego未知
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Boehringer IngelheimEli Lilly and Company完全的
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Boehringer IngelheimEli Lilly and Company完全的