Metformin in Patients With Chronic and Acute Heart Failure: Pharmacokinetics and Polymorphisms in Genes Encoding Membrane Metformin Transporter Proteins
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Mean trough steady-state concentrations of metformin with emphasis on the intra-interindividual variability in HF patients
研究概览
简要总结
The study evaluates the pharmacokinetics of metformin in heart failure patients in acute and chronic state in relation to metformin transporter genotypes. Participants have heart failure and type 2 diabetes treated with metformin.
Hypothesis:
Primary: The renal clearance of metformin is decreased in acute state of congestive heart failure compared with chronic state.
Secondary: Metformin trough values in HF patients are influenced by polymorphisms in transporter genes relevant to the pharmacokinetics of metformin.
详细描述
Background: Heart failure (HF) is a common disease and diabetes/insulin resistance are present in approximately 50 % of HF patients. Metformin is the most commonly prescribed oral anti-diabetic drug, and a huge inter-individual variability in trough steady-state metformin concentration in type 2 diabetics have been demonstrated. Genetic polymorphisms in metformin transporter genes are likely to have a direct impact on metformin pharmacokinetics and variability in drug responses, but the influence of polymorphisms in these transporter genes on circulating metformin levels is presently unknown in HF patients.
Objectives:
A) To compare the pharmacokinetics of metformin in 12 diabetic patients with HF in acute and chronic state.
B) To investigate the influence of polymorphisms in genes encoding the metformin transporter proteins on metformin trough levels in 150 diabetic HF patients.
Design: An open, single-center study enrolling 12 patients with acute heart failure (study A) and 150 patients with stable chronic heart failure (study B). The participants have diabetes already treated with metformin prior to inclusion. Through repeated blood draws, the concentration of metformin will be determined along with genotyping for metformin transporter genes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with heart failure
- •LVEF < 45% within 12 months prior to inclusion
- •NYHA-class I, II, III or IV
- •Ability to understand the written patient information and to give informed consent
- •Diabetes Type 2 (and in metformin treatment for > 1 month)
- •Stable dosage of metformin treatment for at least 1 week prior to examination
排除标准
- •Age < 18 years
- •Current abuse of alcohol or drugs
研究组 & 干预措施
Interventional
All participants
干预措施: Blood draws and urine samples for metformin concentration measurements (Other)
Interventional
All participants
干预措施: Metformin (Drug)
结局指标
主要结局
Mean trough steady-state concentrations of metformin with emphasis on the intra-interindividual variability in HF patients
时间窗: 3 weeks
Changes in renal clearance of metformin between patients with acute and chronic heart failure.
时间窗: approximately 2 weeks
次要结局
未报告次要终点
研究者
Henrik Wiggers
Senior consultant, associate professor, PhD, DMSc
Aarhus University Hospital