Effects of LEAP-2 on Postprandial Glucose Metabolism and Food Intake
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Food intake
研究概览
简要总结
The study aim to delineate the effects of the naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP-2) on postprandial glucose metabolism and food intake in healthy volunteers. The overall objective is to investigate the physiological importance of LEAP-2 in healthy subjects.
详细描述
In a recent study, the molecular phenotype of enteroendocrine cells in the small intestine before and after Roux-en-Y Gastric Bypass (RYGB) surgery in obese individuals was examined. Enteroendocrine cells were identified and isolated from intestinal biopsies and analysed for differentially expressed genes by Illumina High Throughput RNA-sequencing. It was discovered that the gene encoding liver-enriched antimicrobial peptide 2 (LEAP-2), a naturally occurring peptide in humans, was significantly upregulated compared to baseline expression. Interestingly, LEAP-2 was recently shown to antagonize ghrelin function in response to feeding in mice. Moreover, the mature murine LEAP-2 peptide is identical in mice and humans. Thus, LEAP-2 has been identified as an endogenous peptide that may be able to alter feeding behaviour and maintenance of glucose levels during calorie restriction.
The study hypothesis is that LEAP-2 alters postprandial glucose metabolism and decreases appetite as well as food intake in relation to a liquid mixed meal and a standardised ad libitum meal compared with saline (placebo) in healthy subjects.
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 20-35 kg/m2
- •Informed consent
排除标准
- •Anaemia (haemoglobin below normal range)
- •Alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary and/or gastrointestinal disorder(s)
- •Nephropathy (serum creatinine above normal range and/or albuminuria)
- •Allergy or intolerance to ingredients included in the standardised meals
- •First-degree relatives with diabetes and/or glycated haemoglobin (HbA1c) >48 mmol/mol
- •Regular tobacco smoking or use of other nicotine-containing products
- •Any ongoing medication that the investigator evaluates would interfere with trial participation.
- •Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses
结局指标
主要结局
Food intake
时间窗: 260 to 290 minutes
Difference in food intake during an ad libitum meal. Food intake is examined as kilojoules (kJ) and kJ/kg body weight of food eaten during the ad libitum meal.
次要结局
- Alterations in gastric emptying(-30 to 290 minutes)
- Changes in resting energy expenditure (REE)(-30 to 290 minutes)
- VAS(-30 to 290 minutes)
- Plasma insulin levels and beta cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration(-30 to 290 minutes)
- Free fatty acid responses(-30 to 290 minutes)
- Plasma/serum concentrations of LEAP-2, acyl-ghrelin as well as other glucose- and appetite-regulating gut hormones(-30 to 290 minutes)
- Assessment of nitrogen balance and protein breakdown in urine(-30 to 290 minutes)
- Triglyceride responses(-30 to 290 minutes)
- Cholesterol responses(-30 to 290 minutes)
研究者
Filip Krag Knop
Professor, head of department
University Hospital, Gentofte, Copenhagen