A Pathophysiological Study of the Postprandial Human Liver (PLS)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 87
- 试验地点
- 1
- 主要终点
- Postprandial phosphoproteomic changes in liver tissue in healthy individuals
研究概览
简要总结
Fatty liver disease is a globally widespread disease. The identification of valid biomarkers and targets for potential treatments requires in-depth knowledge about the pathophysiology of the postprandial liver. The study will consist of seven work packages (WP) including blood tests and liver biopsies taken after fasting or ingestion of a standardized meal in: healthy controls (WP 1), patients with NAFLD (WP 2), and patients with cirrhosis (WP 3) ; before and after a standardised meal in healthy controls (WP 4), and before and after glucagon in healthy controls (WP5), patients with NAFLD (WP6), and patients with T2DM and NAFLD (WP7).
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants (WP1 , WP4 , WP5 ):
- •Inclusion criteria: Healthy adults, 20 - 40 years old, non-smoker, BMI 20-25 kg/m2 , no chro-nical illnesses, no medication.
排除标准
- •Blood donation within the past 3 months, acute illness within 2 weeks.
- •NAFLD (WP2, WP6):
- •Inclusion criteria: Patients with clinical diagnosis of NAFL and indication for liver biopsy. Exclusion criteria: Malignant disease, acute illness within the past 2 weeks.
- •Cirrhosis (WP 3):
- •Inclusion criteria: Patients with clinical diagnosis of cirrhosis and indication for liver biopsy. Exclusion criteria:Malignant disease, acute illness within the past 2 weeks.
- •T2DM and NAFLD (WP7):
- •Inclusion criteria: Patients with clinical diagnosis of T2DM and NAFL and indication for liver biopsy. Exclusion criteria: Malignant disease, acute illness within the past 2 weeks and use of insulin.
研究组 & 干预措施
Blood tests and liver biopsies after fasting or ingestion of a standardized meal
Participants randomized to the meal group consume, over a period of five minutes, a standardized liquid meal (Nutridrink Standard, 200 mL, 300 kcal, Nutricia). Participants randomized to the fasting group remain fasted for one hour after arrival. A transjugular liver biopsy is then performed at minute 60. Blood samples are obtained throughout the study day.
干预措施: Standardised meal (Dietary Supplement)
Blood tests and liver biopsies before and after a standardized meal
A transjugular liver biopsy is performed, followed by ingestion of a standardized liquid meal (Nutridrink Standard, 200 mL, 300 kcal, Nutricia; 16% protein, 49% carbohydrate, 35% fat). A second transjugular liver biopsy is then performed 30 minutes after meal ingestion. Blood samples are obtained throughout the study day.
干预措施: Standardised meal (Dietary Supplement)
Blood tests and liver biopsies before and after a bolus of glucagon
A transjugular liver biopsy is performed, followed by an intravenous bolus of 0.2 mg glucagon. A second transjugular liver biopsy is then performed 30 minutes after meal ingestion. Blood samples are obtained throughout the study day.
干预措施: Glucagon bolus (Drug)
结局指标
主要结局
Postprandial phosphoproteomic changes in liver tissue in healthy individuals
时间窗: 60 minutes after the meal administered at the study day
Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy individuals.
次要结局
- Postprandial phosphoproteomic changes in liver tissue between healthy participants and patients with cirrhosis or patients with NAFLD.(60 minutes after the meal administered at the study day)
- Postprandial proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals and compared to patients with cirrhosis and patients with NAFLD(60 minutes after the meal administered at the study day)
- Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with cirrhosis and patients with NAFLD(120 minutes after the meal administered at the study day)
- Postprandial phosphoproteomics, proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals.(30 minutes after the meal administered at the study day)
- Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals.(120 minutes after the meal administered at the study day)
- Effect of exogenous glucagon on changes in liver phosphoproteomics, proteomics, metabolomics, and transcriptomics in healthy individuals and compared to patients with NAFLD and patients with T2DM and NAFLD.(30 minutes after the glucagon administered at the study day)
- Effect of exogenous glucagon on changes in phosphoproteomics, proteomics, metabolomics and peptidomic in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with NAFLD and patients with T2DM and NAFLD(120 minutes after the glucagon administered at the study day)
研究者
Lise Gluud
Consultant hepatologist
Copenhagen University Hospital, Hvidovre