Bromocriptine and Insulin Sensitivity in Lean and Obese Subjects
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Timing of administration of bromocriptine
研究概览
简要总结
In this study the investigators will examine the effect of dopamine (bromocriptine) on insulin sensitivity in lean and obese subjects. Furthermore, the investigators will examine whether the timing of bromocriptine administration has influence on insulin sensitivity.
To do so, the investigators will include lean and obese subjects who will use 2 times 2 weeks bromocriptine. In randomized order, they will use it in the morning or in the evening.
The investigators will examine insulin sensitivity by performing a 7-point oral glucose tolerance test.
Furthermore, the investigators will examine energy expenditure and subjects will keep track of their eating behaviour in the 3 days before each study visit.
详细描述
Bromocriptine, a dopamine 2 receptor agonist, has recently been approved in the treatment of type 2 diabetes mellitus(DM2). Bromocriptine causes a significant improvement of fasting plasma glucose and Hba1C values. The exact mechanism of action of bromocriptine is still unknown.
Earlier, the investigators performed a study to show the effects of bromocriptine on brown adipose tissue (BAT) activity (the DEBAT study (Medisch Etische Toetsingscommissie) METC nr 2013_107). Namely, BAT, known for its capacity to dissipate excess energy, might have been involved in this process as stimulation by the sympathetic nervous system is the principal driving force in controlling BAT activity. However, the investigators have shown that bromocriptine did not influence BAT activity or energy expenditure in healthy, lean subjects.
The investigators did found an effect of bromocriptine on insulin sensitivity unexpectedly, subjects became significantly less insulin sensitive after bromocriptine use.
Circadian neuroendocrine rhythms, especially the dopaminergic and serotonergic neurotransmitter activity, play a pivotal role in the development of seasonal and non-seasonal changes in body fat stores and insulin sensitivity. Therefore, the timing of bromocriptine administration might be of great importance in changes in insulin sensitivity. Indeed, in the treatment for DM2, a bromocriptine quick release variant is given in the morning. In the former study the investigators instructed the subjects to use the bromocriptine in the evening in combination with the evening meal. The investigators decided to do so because bromocriptine had to be taken in combination with food. The investigators wanted a high level of dopamine just before the 18F-Fludeoxyglucose(18F-FDG) positron emission tomography (PET) computed tomography (CT) scan to get a maximum effect of dopamine on BAT. But the subjects had to be fasted for the OGTT and 18F-FDG-PET-CT scan. Therefore, the investigators decided to give the (long-acting) bromocriptine in the evening.
Also, the effect of bromocriptine might be different in lean or obese subjects. Obesity is associated with an increased sympathetic tonus. Therefore, the baseline condition is different in lean or obese subjects which may cause different effects of bromocriptine treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 30 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Caucasian origin
- •Subjects should be able and willing to give informed consent
- •BMI range of 19-23 kg/m2 or BMI> 27 kg/2
排除标准
- •Renal failure (creatinine>135mmol/l)
- •Liver failure (ASAT/ALAT > 3 times higher than the normal upper value)
- •Daily use of prescription medication
- •Known hypersensitivity to bromocriptine.
- •Uncontrolled hypertension
- •Known history of coronary artery disease or valvulopathy
- •History of severe psychiatric disorders.
- •Prolactin-releasing pituitary tumor (prolactinoma).
研究组 & 干预措施
Morning bromocriptine
Bromocriptine is taken in the morning
干预措施: Bromocriptine (Drug)
Evening bromocriptine
Bromocriptine is taken in te evening
干预措施: Bromocriptine (Drug)
结局指标
主要结局
Timing of administration of bromocriptine
时间窗: 6 weeks
To determine whether there is a beneficial effect on insulin sensitivity when bromocriptine is given in the morning, as compared to bromocriptine in the evening in Caucasian, lean and obese males
次要结局
- Difference in energy expenditure in lean and obese before and after the use of bromocriptin(6 weeks)
- Difference in insulin sensitivity between lean and obese males before and after the use of bromocriptin(6 weeks)
研究者
F Holleman
Dr. MD.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)