A Randomized, Double - Blind, Placebo - Controlled Trial to Investigate the Effect of Dapagliflozin on Ischemia Reperfusion Induced Endothelial Dysfunction of the Forearm Vasculature in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Acetylcholine - Area under the curve forearm blood flow measurement
研究概览
简要总结
The aim of the study is to investigate the effect of dapagliflozin or placebo on acetylcholine (Ach)- or nitroglycerin (GTN)-induced vasodilation of the forearm resistance vasculature, as determined by FBF measurement before and 10 minutes after 20 minutes of forearm ischemia.
详细描述
The aim is to test the effect of dapagliflozin or placebo on ACh-induced vasodilatation of the forearm resistance vasculature as assessed by FBF measurement before and 10 min after a 20 min forearm ischemia as well as after a 14 day treatment period. The area under the dose-effect curve (AUC) of different ACh doses will be calculated and compared between treatment groups (dapagliflozin vs. placebo) and different time points (pre-ischemia vs. post-ischemia). FBF measurements will be made in response to increasing intra-arterial doses of ACh (25, 50, 100 nmol/min) to assess endothelial function or GTN (4, 8, 16 nmol/min) to test vascular smooth muscle vasodilator function.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects; 18 - 40 years of age
- •Body mass index between 18 and 27 kg/m2
- •Written informed consent
- •Normal findings in medical history
- •Non-smoking
排除标准
- •Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration
- •History of occlusive vascular diseases
- •History of vascular anomalies
- •History of coagulation disorders
- •History of diabetes mellitus (Type 1&2) or pre-diabetes (i.e. HbA1c ≥ 5,7 %)
- •History of kidney disease
- •History of ketoacidosis
- •Impaired liver function (AST, ALT, gGT, bilirubin >3 x ULN)
- •Impaired renal function (serum creatinine > 1.3 mg/dl)
- •Any other relevant deviation from the normal range in clinical chemistry, haematology or urine analysis
- •HIV-1/2-Ab, HbsAg or HCV-Ab positive serology
- •Systolic blood pressure above 145 mmHg, diastolic blood pressure above 95 mmHg
- •Known allergy against any test agent under study and/or lactose intolerance
- •Regular daily consumption of more than on litre of xanthine-containing beverages or more than 40g alcohol
- •Participation in another clinical trial during the preceding 3 weeks
研究组 & 干预措施
Dapagliflozin
14 day orally treatment with dapagliflozin
干预措施: Dapagliflozin 10mg (Drug)
Dapagliflozin-placebo
14 day orally treatment with dapagliflozin - placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Acetylcholine - Area under the curve forearm blood flow measurement
时间窗: 30 min
acute effect of dapagliflozin on forearm blood flow (FBF) reactivity in response to the vasodilators acetylcholine (ACh; endothelium-dependent agonist) or nitroglycerin (GTN; endothelium-independent vasodilator) 10 min before (baseline) and after 20 min forearm ischemia, respectively.
次要结局
未报告次要终点
研究者
Michael Wolzt, Prof. MD
Univ. Prof. Dr.
Medical University of Vienna