The Role of the Kidneys and Liver in the Elimination of Glucagon An Evaluation of the Metabolic Clearance Rate of Glucagon in Patients With End-stage Renal Disease and Patients With Liver Cirrhosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Metabolic clearance rate of glucagon
研究概览
简要总结
The study aims to evaluate the kinetics and effect of glucagon in patients with chronic kidney disease and liver cirrhosis and matched healthy subjects, respectively.
详细描述
In the present project the investigators wish to identify whether the effect, elimination and degradation of glucagon differ between healthy control subjects and patients with Chronic Kidney Disease (CKD) and liver cirrhosis, respectively. By performing glucagon infusions on healthy control subjects and matched subjects with either limited renal and hepatic function, the contribution of both organs to the metabolic clearance rate (MCR) of glucagon can be tested. A primed infusion of stable isotopic labelled tracers will allow the researchers to investigate the effects of the glucagon infusion on the glucose, lipid and amino acid metabolism.
The quantification of the MCR of glucagon will be accompanied by a range of pharmacodynamic measures in order to substantiate whether a potentially altered glucagon MCR inflicts pharmacodynamic changes of glucagon, which could contribute to the pathophysiology of CKD and liver cirrhosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •The CKD group
- •Men/women between 18 and 75 years of age
- •CKD stage 4 or 5
- •Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range,
- •Informed consent
- •The cirrhosis group
- •Men/women between 18 and 75 years of age
- •Verified diagnosis of cirrhosis - Child-Pugh Score of 5-12
- •Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)
- •Informed consent
- •The control group
- •Men/women between 18 and 75 years of age
- •Normal kidney function (estimated glomerular filtration rate (eGFR) above 60 ml/min/1.73m2 and absence of proteinuria)(plasma creatinine ≤105 micromol/L (µM) for men and ≤90 µM for women)
- •Normal liver function (alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), albumin and coagulation factor II, VII and X (INR) within normal range
- •Informed consent
排除标准
- •Diagnosis of diabetes and/or HbA1c ≥43 mmol/mol and/or fasting plasma glucose ≥6 mmol/l.
- •Previous kidney transplantation with remaining kidney graft
- •Present treatment with oral glucocorticoids
- •Polycystic kidney disease
- •Pregnancy or breastfeeding
- •Inflammatory bowel disease
- •Surgical procedure within the last 3 months
- •Haemoglobin < 6 mmol/l (women) or < 7 mmol/l (men)
- •First-degree relatives with diabetes
- •Any condition that the investigators feel would interfere with trial participation
结局指标
主要结局
Metabolic clearance rate of glucagon
时间窗: t = 50 minutes
Glucagon plasma concentration steady state glucagon concentrations
次要结局
- Glucagon pharmacokinetic 2(-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes)
- Glucagon pharmacodynamic - amino acids(-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes)
- Vital parameter 2(-120, -30, 0, 60, 120 minutes)
- Vital parameter 3(-120, -30, 0, 60, 120 minutes)
- Glucagon pharmacokinetic 1(-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes)
- Glucagon-like peptide 1(-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes)
- Lipid metabolism(-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes)
- Glucagon pharmacodynamic - glucose(-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes)
- Vital parameter 1(-120, -30, 0, 60, 120 minutes)
- Tracers(-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120)
- Insulin(-120, -90, -60, -30, -15, 0, 5, 10, 20, 50, 55, 60, 62, 64, 66, 68, 70, 75, 80, 85, 90, 120 minutes)
研究者
Magnus Frederik Gluud Grøndahl
Principal investigator, Medical Doctor
University Hospital, Gentofte, Copenhagen