Effects of KATP Channel Blockers on GLP-1 and Its Analogues' Mediated Microvascular Function
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Change in skin blood flow to GLP-1 and its analogues
研究概览
简要总结
This study aims to examine the involvement of KATP channels on the microvascular actions of the incretin GLP-1 and its analogues in healthy individuals and to determine whether the acute oral administration of different KATP channel blockers which are oral medications for Type 2 diabetes such as Glibenclamide and Glimepiride differentially modulate the microvascular responses in these individuals.
详细描述
In addition to the glucose lowering effect, incretin based therapies have also an effect on the vascular system. Previous animal work and initial human studies suggest that incretins may be cardioprotective and act as vasodilators through opening of KATP channels.
Initial evidence suggests that beneficial vascular effects of incretin modifying agents may be nullified by the co-current treatment of the sulfonylurea (SU) drug glibenclamide. The investigators hypothesis is that the GLP-1 and SUs may have conflicting effects on the KATP channels and thus vascular function.
Interestingly the vascular actions of GLP-1 were not modified by a different treatment SUs called glimepiride, thereby raising the possibility that SUs differentially modulating the vascular actions of GLP-1 though this remains controversial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Health Services Research
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI ≤ 25 kg/m2
排除标准
- •current or past history of diabetes (HbA1C more or equal 45mmol/mol)
- •history of postprandial hypoglycaemia and dumping syndrome
- •established cardiovascular disease
- •established cerebrovascular disease
- •blood pressure ≥ 140/85 mmHg
- •Raynaud's disease
- •severe impairment of renalhepatic, thyroid or adrenocortical function
- •current treatment with any anti-hypertensive treatment
- •lipid lowering therapy or systemic steroids
- •lactation, pregnancy
- •established vascular disease
- •bariatric surgery
- •significant weight change within the last 3 months
研究组 & 干预措施
Glimepiride
4mg of Glimepiride once only before vascular testing and intradermal injections of GLP-1 and its analogues
干预措施: Intradermal injections of GLP-1 and its analogues (Other)
Placebo tablet
Placebo tablet is given in the morning of the intradermal injections of GLP-1 and its analogues
干预措施: Intradermal injections of GLP-1 and its analogues (Other)
Glyburide
10mg of Glyburide before study visit and intradermal injections of GLP-1 and its analogues
干预措施: Intradermal injections of GLP-1 and its analogues (Other)
结局指标
主要结局
Change in skin blood flow to GLP-1 and its analogues
时间窗: 6 weeks
Skin blood flow will be assessed before and after microinjection of GLP-1 or its analogues and the injection site monitored and compared to sites injected with placebo
次要结局
未报告次要终点
研究者
Katarina Kos
Senior Lecturer
Royal Devon and Exeter NHS Foundation Trust