A Leap to Understand Glucoregulatory Effects of Liver-enriched Antimicrobial Peptide 2 (LEAP-2)
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Plasma insulin
研究概览
简要总结
The investigators aim to investigate the physiological importance of LEAP-2 in healthy volunteers focusing on its potential insulinotropic effects.
详细描述
The dramatic and almost immediate effects of Roux-en-Y gastric bypass (RYGB) surgery on type 2 diabetes (T2D) can only in part be explained by alterations in the plasma concentrations of known peptides. Thus, other - yet unknown - signals or hormones elicited from the endocrine cells of the small intestine may play an important role for the remission of T2D observed following RYGB. In a recent study, a predicted sequence of liver-enriched antimicrobial peptide 2 (LEAP-2) was shown to induce a glucose-stimulated insulin secretion in isolated human pancreatic islets. The fragment was subsequently identified to be circulating in human plasma in concentrations comparable to the circulating levels of other known gut secreted hormones, hereby validating that LEAP-2 is an endogenous circulating peptide.
The investigators hypothesise that LEAP-2 increases insulin secretion during a graded glucose infusion as assessed by plasma insulin and C-peptide compared with saline (placebo) in healthy subjects. The study is designed as a clinical, placebo-controlled, double-blinded cross-over study involving two experimental study days and ten young healthy male participants. The co-primary endpoints are the difference in plasma insulin levels during a graded glucose infusion and beta-cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration between the two study days with either saline (placebo) or LEAP-2 infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Day A and B will be conducted in a randomised, double-blinded order (blinded for the participant and the investigator) and noted by a third person not participating in the collection or analyses of data. The infusion order will be opened after the primary data analyses.
入排标准
- 年龄范围
- 18 Years 至 25 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Caucasian men
- •Age between 18 and 25 years
- •Body mass index between 20-25 kg/m2
- •Informed consent
排除标准
- •Anaemia (haemoglobin below normal range)
- •ALAT and/or ASAT >2 times normal values or history of hepatobiliary and/or gastrointestinal disorder(s)
- •Nephropathy (serum creatinine above normal range and/or albuminuria)
- •Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses
- •Any ongoing medication that the investigator evaluates would interfere with trial participation.
- •First- and second-degree relatives with diabetes
- •Regular tobacco smoking
结局指标
主要结局
Plasma insulin
时间窗: -45 to 180 minutes
Difference in plasma insulin levels
Beta-cell secretion
时间窗: -45 to 180 minutes
Beta-cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration
次要结局
- Appetite, satiety, and general well-being(-45 to 210 minutes)
- LEAP-2(-45 to 210 minutes)
- Resting energy expenditure(-20 to 160 minutes)
研究者
Filip Krag Knop
Professor, head of department
University Hospital, Gentofte, Copenhagen