A Single Centre, Placebo Controlled, Phase I Study to Evaluate the Effect of Glucose and Moxifloxacin on Cardiac Repolarisation in Male and Female Patients With Type I Diabetes.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- ECG Analysis
研究概览
简要总结
High blood glucose levels (hyperglycaemia) and Moxifloxacin (a commonly used antibiotic) have both been shown independently to affect heart activity in healthy volunteers as recorded by ECG. i.e. Both cause prolongation of the QTc interval which is a measure of the time between the start of the Qwave and the end of the Twave during a heartbeat cycle. In this study, the investigators want to find out whether moxifloxacin and hyperglycaemia cause QTc prolongation in Type 1 diabetic patients. The investigators also want to assess whether C-peptide (a fragment if insulin normally found in the blood but not present in the blood of Type 1 diabetics) has the opposite effect on heart activity i.e it shortens the QTc interval will reverse the effect of QTc prolongation in Type 1 diabetes as this may be useful for preventing 'dead in bed' syndrome also known as 'Sudden Cardiac Death' which is more common in diabetic patients compared to healthy volunteers.
详细描述
The investigators previous research (Taubel et al., 2013) has shown that in healthy individuals glucose by itself can prolong (with C-peptide antagonising the effects) the QT interval, which has long been used as a clinical index of the duration of ventricular repolarisation. This observation warrants serious attention because it suggests that high glucose levels by themselves may be pro-arrhythmogenic. To investigate whether glucose has an effect on cardiac repolarisation, it would be advantageous to test this in an environment uncomplicated by C-peptide. In order to elucidate the effects of glucose on the QTc in the absence of C-peptide, the investigators will use diabetic patients who are no longer able to release endogenous C-peptide. This will allow better understanding to whether (1) the well established QTc prolongation caused by moxifloxacin is exaggerated by elevated levels of blood glucose, which would be important for evaluating the risk in diabetic patients using an IKr blocking drug such as moxifloxacin, and (2) to investigate whether C-peptide substitution will reverse or attenuate the effect in the presence of moxifloxacin. Using the conditions of a formal TQT study, the investigators would also want to confirm the QTc prolonging effects described in Gordin et al. (2008) and whether in this setting C-Peptide substitution will reverse or attenuate the glucose effect on QTc.
This will be a phase I, single centre, randomised, placebo-controlled, open-label, crossover study designed to evaluate the effect of glucose and C-peptide on cardiac repolarisation using a hyperglycaemic clamp and a single 400 mg dose of moxifloxacin as a positive control in non-elderly male and female patients with type I diabetes. The results from this study will form the basis for decisions for future studies.
This study will be performed in compliance with the protocol, ICH GCP and applicable regulatory requirements including EU GMP requirements for investigational medicinal product(s) (IMPs).
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
- None
入排标准
- 年龄范围
- 20 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
hyper-glycaemic clamp:
hyper-glycaemic clamp: intra-venous Glucose as an initial bolus of 250mg/kg followed by a variable maintenance infusion for 4 hours
干预措施: hyper-glycaemic clamp (Other)
Moxifloxacin
Single oral dose of 400 mg Moxifloxacin
干预措施: Moxifloxacin (Drug)
Placebo
Placebo
干预措施: Moxifloxacin (Drug)
结局指标
主要结局
ECG Analysis
时间窗: 1, 2, 3 Days
* The paired PK and QTc interval parameters pre-dose compared to post-administration of glucose. Clinically significant ECG morphology and interval changes from baseline. * The effect on QTc will be calculated using concentration-effect analysis.
次要结局
- Proportion of Participants with Adverse Events(1, 2, 3 Days)