Neuronostatin - a Glucagonotropic Agent in Humans?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Total glucagon response
研究概览
简要总结
With the present study the investigators wish to delineate the effects of neuronostatin-13 (NST) on glucose-dependent glucagon secretion in humans. The main question it aims to answer is:
• What are the physiological effects of the naturally occuring hormone NST - especially with regards to glucagonotropic effects at different plasma glucose concentrations
In a randomized, double-blind crossover design, participants will undergo six experimental days with controlled plasma glucose levels, consisting of two euglycemic, two hyperglycemic (around 8mmol/l), and two hypoglycemic (around 2.5mmol/l) days, with each pair of similar days involving the administration of either saline (placebo) or NST.
详细描述
With the present study the investigators wish to delineate the effects of neuronostatin on glucose-dependent glucagon secretion in humans. Thus, this study is designed to elucidate the physiological effects of the natural occurring hormone, neuronostatin, and not to examine a medical effect of a drug or treatment. However, if neuronostatin acts glucagonotropically during low plasma glucose concentrations it could potentially help to address the unmet medical need for a treatment that, ultimately, can counteract the high risk of hypoglycaemia in patients treated with insulin.
After being informed about the study and the potential risks, each participant giving written informed consent will participate in six double-blinded experimental days (Day A-F) in a randomized order. On each day, participants will receive an infusion of either saline (placebo)(day A, C and E) or NST (day B, D and F). On day A and B, blood glucose will be kept at fasting levels, on day C and D blood glucose will be increased to ~8mmol/l and on day E and F blood glucose will be lowered to ~2.5mmol/l.
Blood glucose will be adjusted with insulin and/or glucose to reach the desired levels on each day.
At the end of the study day, participants will receive an ad libitum meal.
The effects of each infusion will be evaluated with regards to glucagonotropic potency, as well as a series of exploratory outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
The randomized order of infusions is blinded to both participant and investigator
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Normal haemoglobin >8.3 mmol/l
- •Normal fasting plasma glucose below 7 mmol/l
- •Normal HbA1C <42 mmol/mol (6%)
- •Body mass index (BMI) 18.5-27 kg/m2
- •Oral and written informed consent
排除标准
- •Treatment with drugs that might interfere with glucose metabolism within a month prior to the research study
- •Treatment with any medication that cannot be paused for 12 hours
- •Known liver disease and/or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 × normal values
- •Nephropathy (eGFR <60 ml/min and/or albuminuria)
- •Any condition that the investigator feels would interfere with trial participation
结局指标
主要结局
Total glucagon response
时间窗: 0-150minutes
Differences in glucagon responses, measured as baseline subtracted AUC (bsAUC), between days with neuronostatin and placebo at corresponding glucose concentrations, respectively
次要结局
- Difference in epinephrine(0-150minutes)
- Glucagon response during hypoglycemia(t[BG=3.0] and the following 30 minutes)
- Energy expenditure(At -20 minutes, at 30 minutes, and at 75 minutes)
- Food intake(At 125 minutes)
- Glucagon response during "recovery"(60-90minutes)
- Total proinsulin-c-peptide response(0-150minutes)
- Difference in growth hormone(0-150minutes)
- Difference in osteocalcin(0-150minutes)
- Total insulin response(0-150minutes)
- Amount of glucose infused(0-150minutes)
- Appetite(At -5 minutes, 25 minutes, 60 minutes, 90 minutes, and 120minutes)
- Glucagon response during first 60 minutes(0-60minutes)
- Difference in norepinephrine(0-150minutes)
- Difference in cortisol(0-150minutes)
- Difference in Procollagen 1 Intact N-Terminal Propeptide (P1NP)(0-150minutes)
- Difference in carboxy-terminal collagen crosslinks (CTX)(0-150minutes)
- Difference in heart rate(0-150minutes)
- Difference in blood pressure(0-150minutes)
研究者
Asger Lund, MD
MD
University Hospital, Gentofte, Copenhagen