Investigation of the Cardiovascular Effects of Exenatide in Healthy Male Subjects
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- superior mesenteric (SMA) blood flow
研究概览
简要总结
Exenatide is a new drug which lowers blood sugar (glucose) levels for people with type 2 diabetes. It has significant advantages over other treatments such as insulin as it causes weight loss in a group of people that is generally overweight. Data from studies involving exenatide have shown that it also has an effect on blood pressure. The mechanism for the blood pressure lowering effect is not known and has not been investigated previously. Exenatide may have an effect on blood vessels throughout the body and gut to reduce blood pressure. 12 healthy men (18-45yr) will be studied on 2 occasions. Limb blood flow, skin blood flow, gut blood flow, blood pressure, and heart rate will be measured half hourly for 4 hours. Blood samples (3ml) for insulin and glucose determination will be taken via a cannula and 3-way tap at the same time points. A dose of either 5μg exenatide or saline will be injected under the skin of the abdomen and a breakfast will be provided during the study. A urine collection will be made over the duration of the study.
详细描述
Background:
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the L-cells of the gut following a meal (1). GLP-1 has multiple modes of action, including to augment the usual rise in insulin release and decrease in glucagon that follows carbohydrate ingestion (2). GLP-1 therefore plays a part in glucose homeostasis. GLP-1 secretion is reduced in patients with type 2 diabetes (T2DM) and extended-action GLP-1 agonists or mimetics are currently being introduced for use as glucose lowering medications. The peptide exendin-4 has considerable homology with GLP-1 but is resistant to degradation by the enzyme Dipeptidyl peptidase-4 (DPP-IV) and so has a much longer duration of action. The synthetic exendin, 'Exenatide', is a novel GLP-1 mimetic which has recently been licensed for the treatment for T2DM and has shown to be an effective glucoregulatory agent when administered as a twice- daily subcutaneous injection (11).
GLP-1 agonists give a low risk of significant hypoglycaemia as effects on insulin and glucagon are largely glucose-dependent. In addition, considerable weight loss is often observed with GLP-1 agonists in clinical practice, and these drugs are currently being considered in treating obesity, even outside the context of diabetes.
A moderate blood-pressure (BP) lowering effect of GLP-1 agonists has also been noted as a secondary outcome measure in large clinical trials in patients with T2DM. In one such study, Exenatide was associated with a reduction in systolic/diastolic BP of 5/2 mmHg The mechanism for this apparent hypotensive effect is not known. An infusion of GLP-1 agonists induces a natriuresis, which may contribute to a reduction in BP.
Aims:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •non-obese (BMI 20-27: those with a BMI > 25 will be excluded if they have a waist circumference > 90cm),
- •aged 18-45yrs,
- •non-smoker.
排除标准
- •any metabolic or endocrine abnormalities,
- •clinically significant abnormalities on screening,
- •taking regular medication.
研究组 & 干预措施
0.9% Saline
subcutaneous administration of 0.9% saline solution (0.02 ml)
干预措施: Saline (Drug)
Exenatide
subcutaneous administration of Exenatide (0.02ml)
干预措施: Exenatide (Drug)
结局指标
主要结局
superior mesenteric (SMA) blood flow
时间窗: 0, 30, 60, 90, 120, 150, & 180 min after meal
Meal induced changes in superior mesenteric (SMA) blood flow - exenatide versus placebo.
次要结局
- Heart Rate (HR)(0, 30, 60, 90, 120, 150, & 180 min after meal)
- Peripheral resistance(0, 30, 60, 90, 120, 150, & 180 min after meal)
- Blood Pressure (BP)(0, 30, 60, 90, 120, 150, & 180 min after meal)
- Limb Blood Flow (LBF)(0, 30, 60, 90, 120, 150, & 180 min after meal)
- Skin Blood Flow(0, 30, 60, 90, 120, 150, & 180 min after meal)
研究者
Elizabeth Simpson
Senior Research Fellow
University of Nottingham