A Parallel, Double-blinded, Randomized, 6 Months, Two Arms Study With Lifestyle Intervention and Bydureon® or Lifestyle Intervention and Placebo in Adolescents With Obesity to Explore Differences With Regard to Change in BMI SDS
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- BMI SDS (Body Mass Index Standard Deviation Score)
研究概览
简要总结
Combat-JUDO (Combating Juvenile Diabetes and Obesity through normalization of beta-cell function) is part of a collaborative project funded by the Seventh Framework Programme of the European Commission aiming to develop innovative therapeutic strategies by increasing pharmacology-based alternatives targeting insulin hypersecretion for the treatment of young obese individuals.
The prevalence of childhood obesity is ranging between 5-25% in Europe. The reason behind these alarming figures is mostly a changing environment with a more sedative lifestyle and supply of excess food. However, specific gene mutations have also been linked to obesity and new genes are continuously being discovered. There are very few effective means of intervention in children with obesity available today. Obesity is closely associated with a number of related metabolic diseases and some children with obesity develop the metabolic syndrome at an early stage in life. Individuals with obesity have an increased risk of developing type 2 diabetes mellitus (T2DM) and with the current increase in childhood obesity, some children will develop T2DM already in their adolescent years with huge impact on their long-term health and life expectancy.
Lifestyle modification interventions, including behavioural treatment, diet modification and physical activity, are cornerstones of primary and secondary prevention/treatment of pediatric obesity today. Exenatide is a GLP-1 (glucagon-like peptide-1) receptor agonist approved for use in adults with T2DM to improve glycemic control. A pilot study with exenatide treatment in non-diabetic children and adolescents with severe obesity showed a reduced BMI of approximately 5% and improved markers of insulin resistance and β-cell function were observed.
The Combat-JUDO study is a parallel, double-blind, randomized study comparing lifestyle intervention + exenatide 2 mg vs lifestyle and intervention + placebo in adolescents with obesity. The lifestyle intervention includes regular nutritional and psychological support at 4 occasions during the study as well as physical activity on a weekly basis. Exenatide/placebo is given as a subcutaneous injection once weekly for 24 weeks. The primary objective of the study is to compare the change in BMI-SDS (according to WHO) from baseline to the 6 months visit between the two treatment arms.
The study includes males and females of age 10-18 years and 5 months with BMI SDS >2.0 or age-adapted BMI >30 kg/m2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent prior to any study-specific procedures.
- •Males or females of age 10-18 years and 5 months.
- •Obesity (BMI SDS > 2.0 or age-adapted BMI > 30 kg/m2), according to WHO.
- •Not sexually active or usage of adequate anticonception. Female subjects must also have negative pregnancy tests. Methods that can achieve a failure rate of less than 1% per year (Pearl index <1), when used consistently and correctly, are considered as highly effective birth control methods. Such methods include:
- •Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- •intravaginal
- •transdermal
- •Progestogen-only hormonal contraception associated with inhibition of ovulation:
- •injectable
- •implantable
- •Intrauterine device (IUD)
- •Intrauterine hormone-releasing system (IUS)
- •Bilateral tubal occlusion
- •Vasectomised partner Sexual abstinence (if refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the preferred and usual lifestyle of the subject).
- •Ability to understand and comply with the requirements of the study.
排除标准
- •Known syndromal obesity, such as Prader-Willi syndrome, Laurence-Moon syndrome or Bardet-Biedl syndrome.
- •Pregnancy or lactation.
- •Indigestion-causing diseases.
- •Severe gastrointestinal disease.
- •Total or partial gastric or small intestine resection.
- •Type 1 or Type 2 diabetes mellitus.
- •Kidney disease (acute or chronic, according to physician (Creatinin/Urea/Cystatin-C for Schwartz Calculation)).
- •Hypo-/Hyperthyroidism, unless under stable treatment.
- •Severe Vitamin D insufficiency, unless under stable treatment.
- •Abnormal QT interval.
- •Clinically significant abnormal laboratory values, e.g. Triglycerides > 400 mg/dl (Salzburg) or > 4,5 mmol/L (Uppsala), Amylase > 300 U/L (Salzburg) or > 5,1 µkat/L (Uppsala), Lipase > 180 U/L (Salzburg) or > 15 µkat/L (Uppsala) or Calcitonin > 11.7 pg/ml (Salzburg) or > 3,4 pmol/L (Uppsala) for females and > 17 pg/ml (Salzburg) or > 5,0 pmol/L (Uppsala) for males.
- •Severe depression, severe anxiety or other psychiatric disorder referred to or undergoing special treatment, as judged by the investigator.
- •Severe sleep apnea (defined clinically).
- •Chronic diseases, as judged by the investigator.
- •Metformin treatment within 3 months prior to screening or concomitant medication influencing blood glucose (e.g. metformin and acarbose), influencing other parameters of metabolic syndrome (e.g. orlistat) or interfering with the investigational medicinal product.
- •Steroid treatment (oral or injected).
- •Concomitant medication addressing attention disorders.
- •Antidepressants that can lead to weight gain, as judged by the investigator.
- •Hypersensitivity to exenatide or to any of the excipients.
- •Pacemaker or metal implant that may interfere with Magnetic Resonance Imaging (MRI).
- •Claustrophobia (Uppsala and Salzburg) or abdominal diameter exceeding an MR gantry diameter of 70 cm (Salzburg).
- •Current or prior (within 3 months) participation in another clinical study involving an Investigational Medicinal Product (IMP).
- •A personal or family history of Medullary Thyroid Carcinoma (MTC)
- •A personal or family history of Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
研究组 & 干预措施
Placebo
s.c. once Weekly
干预措施: Placebo (Behavioral)
Bydureon
s.c. once Weekly
干预措施: Exenatide (Drug)
结局指标
主要结局
BMI SDS (Body Mass Index Standard Deviation Score)
时间窗: 6 months
The primary objective is to compare the change from baseline to the 6 months visit, between lifestyle intervention + exenatide 2 mg once weekly and lifestyle intervention + placebo, in BMI SDS (according to WHO) for adolescents with obesity.
次要结局
未报告次要终点
研究者
Peter Bergsten
Professor
Uppsala University