A Comparison of the Haemodynamic and Metabolic Effects of Intravenous Glucagon-like Peptide-1, Glucagon and Glucagon-like Peptide-1:Glucagon Co-agonism in Healthy Male Participants
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
研究概览
简要总结
The study seeks to explore the cardiovascular effects of co-agonism at two peptide receptors, GLP-1 and glucagon. Glucagon, exenatide and 0.9% saline will be intravenously infused, both in isolation, and combination into healthy male participants. Overall, the aim of the study is to further our understanding on the role these endogenous substances play (both in isolation and combination) in haemodynamic regulation.
详细描述
Co-agonist peptides (such as at the GLP-1:glucagon receptor) are currently in clinical development for type 2 diabetes with the dual intention of reducing body weight and controlling blood glucose. However, there is a lack of data on the effects that co-agonism has on haemodynamic regulation.
Part A - Healthy male participants, by acting as their own control, will attend for two intravenous infusion visits (combination of 0.9% saline and glucagon). These will occur in a predefined but random order so that participants will be blinded to the infusion they are receiving. Each infusion visit will comprise of 15 minute baseline followed by a 120 minute infusion. Detailed non-invasive cardiovascular measurements (including peripheral/central blood pressure, heart rate, stroke volume, heart rate variability) and bloods (including insulin, glucose, GLP-1, glucagon) will be collected as part of the study. It was previously planned that GLP-1 7-36 amide 0.6pmol/kg/min and 1.2pmol/kg/min would be infused for Part A resulting in 5 infusions (rather than current 2 infusions). However due to supply/technical issues this was not possible and therefore exenatide (GLP-1 receptor agonist) shall be used in Part B.
Part B - Healthy male participants, by acting as their own control, will attend for four intravenous infusion visits (combination of 0.9% saline, glucagon, exenatide). These will occur in a predefined but random order so that participants will be blinded to the infusion they are receiving. Each infusion visit will comprise of 15 minute baseline followed by a 60 minute infusion. Detailed non-invasive cardiovascular measurements (including peripheral/central blood pressure, heart rate, stroke volume, heart rate variability) and bloods (including insulin, glucose, GLP-1, glucagon) will be collected as part of the study.
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
- Single (Participant)
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
- •Written informed consent to participate
- •Aged 18 to 40
- •Current non-smoker
- •BMI >18.0 and <30kg/m2
排除标准
- •Sustained Hypertension (sustained BP >160/100mmHg) or hypotension (systolic BP below 90 mmHg)
- •Clinically significant heart disease
- •Implanted heart pace-maker or implantable cardioverter defibrillator (ICD)
- •Known active malignancy
- •Known renal failure (creatinine >140μmol/L)
- •Known diabetes mellitus (type 1 or 2)
- •Use of vasoactive medications or NSAIDS/aspirin within 24 hours of study visits
- •Use of formal anticoagulant therapy such as, but not limited to, heparin, warfarin or rivaroxaban
- •Current involvement in the active treatment phase of other research studies, (excluding observations/noninterventional)
- •Any other clinical reason which may preclude entry in the opinion of the investigator
研究组 & 干预措施
Part B - Infusion A
A 60 minute intravenous infusion of 0.9% saline
干预措施: Saline 0.9% (Drug)
Part A - Infusion A
- 60 minute intravenous infusion of 0.9% saline
Followed by: 2. 60 minute intravenous infusion of 0.9% saline
干预措施: Saline 0.9% (Drug)
Part A - Infusion B
- 60 minute intravenous infusion of glucagon 25ng/kg/min and 0.9% saline.
Followed by: 2. 60 minute infusion of glucagon 50ng/kg/min and 0.9% saline
干预措施: Saline 0.9% (Drug)
Part A - Infusion B
- 60 minute intravenous infusion of glucagon 25ng/kg/min and 0.9% saline.
Followed by: 2. 60 minute infusion of glucagon 50ng/kg/min and 0.9% saline
干预措施: Glucagon (25ng/kg/min) (Drug)
Part A - Infusion B
- 60 minute intravenous infusion of glucagon 25ng/kg/min and 0.9% saline.
Followed by: 2. 60 minute infusion of glucagon 50ng/kg/min and 0.9% saline
干预措施: Glucagon (50ng/kg/min) (Drug)
Part B - Infusion B
A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes followed by 25ng/min) and 0.9% saline
干预措施: Saline 0.9% (Drug)
Part B - Infusion B
A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes followed by 25ng/min) and 0.9% saline
干预措施: Exenatide (Drug)
Part B - Infusion C
A 60 minute intravenous infusion of glucagon (25ng/kg/min) and 0.9% saline
干预措施: Saline 0.9% (Drug)
Part B - Infusion C
A 60 minute intravenous infusion of glucagon (25ng/kg/min) and 0.9% saline
干预措施: Glucagon (25ng/kg/min) (Drug)
Part B - Infusion D
A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes then 25ng/min) and glucagon (25ng/kg/min)
干预措施: Glucagon (25ng/kg/min) (Drug)
Part B - Infusion D
A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes then 25ng/min) and glucagon (25ng/kg/min)
干预措施: Exenatide (Drug)
结局指标
主要结局
Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
时间窗: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
Heart rate variability (normalised low frequency, LF, high frequency, HF and LF/HF ratio)
次要结局
- Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.(Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks)
研究者
Dr Ian B Wilkinson
Principal Investigator
Cambridge University Hospitals NHS Foundation Trust