IL-1-receptor Antagonist During Cephalic Phase of Insulin Secretion in Health and Type 2 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Change in insulin concentration in blood during the cephalic phase of insulin secretion in healthy individuals
研究概览
简要总结
A prospective, randomized, mixed double- and single-blinded, placebo-controlled, cross-over clinical trial to test whether acute treatment with an IL-1 receptor antagonist impacts insulin secretion over time during the cephalic phase, defined as the first 10 minutes after the first sensorial contact to food, in healthy individuals in healthy humans (Group 1) and in obese patients with type 2 diabetes (Group 2).
详细描述
The role of the immune system in metabolism has been extensively investigated in pancreatic islets and insulin sensitive tissues. However little attention has been given to a potential role of the innate immune system in the cephalic phase of insulin secretion. In humans, the cephalic phase of insulin secretion appear reduced in obesity and in patients with type 2 diabetes.
In this prospective, randomized, mixed double- and single-blinded, placebo-controlled, cross-over clinical trial we aim to test whether acute treatment with an IL-1 receptor antagonist impacts insulin secretion over time during the cephalic phase, defined as the first 10 minutes after the first sensorial contact to food, in healthy individuals in healthy humans (Group 1) and in obese patients with type 2 diabetes (Group 2).
Group 1: After screening, subjects will be randomized to two crossover visits with a washout period of at least 4 days in-between visits and at most two weeks: A) subcutaneous saline injection 3h before an oral standardized meal, B) subcutaneous injection of 100 mg of the IL-1 receptor antagonist anakinra 3h before an oral standardized meal. Treatments will be placebo controlled, crossover, double blinded. The study will be performed in a population of healthy individuals.
Group 2: Same as for Group 1 with the following addition: after the second study day, participant in group 2 will be trained to self-inject the medication for 6 days. On the 7th day, an oral standardized meal test will be performed.
Healthy subjects from group 1 will be matched for sex and age to the diabetic cohort from group 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
Randomized, double-blinded and open-label, placebo-controlled, partly cross-over clinical trial
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
healthy individuals
Two crossover visits with a washout period of at least 4 days in-between visits and at most two weeks: A) subcutaneous saline injection 3h before an oral standardized meal, B) subcutaneous injection of 100 mg of the IL-1 receptor antagonist anakinra 3h before an oral standardized meal. Treatments will be placebo controlled, crossover, double blinded. Standard dose of Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB), i. e. 100 mg/ 0.67 ml s. c. or 0.67 ml of saline s. c. (placebo)
干预措施: Anakinra Prefilled Syringe (Drug)
obese patients with type 2 diabetes
Three crossover visits with a washout period of at least 4 days in-between: A) subcutaneous saline injection 3h before an oral standardized meal, B) subcutaneous injection of 100 mg of the IL-1 receptor antagonist anakinra 3h before an oral standardized meal, C) Additionally, after the second study day, participant in group 2 will be trained to self-inject the medication for 6 days. On the 7th day, an oral standardized meal test will be performed. Standard dose of Anakinra (Kineret®; r-metHuIL-1ra, Swedish Orphan Biovitrum AB), i. e. 100 mg/ 0.67 ml s. c. or 0.67 ml of saline s. c. (placebo)
干预措施: Anakinra Prefilled Syringe (Drug)
结局指标
主要结局
Change in insulin concentration in blood during the cephalic phase of insulin secretion in healthy individuals
时间窗: 10 minutes
Insulin concentration in blood at 0, 3,6 and 10 minutes after ingestion of a standardized meal in healthy individuals.
Change in insulin concentration in blood during the cephalic phase of insulin secretion in obese patients with type 2 diabetes
时间窗: 10 minutes
Insulin concentration in blood at 0, 3, 6 and 10 minutes after ingestion of a standardized meal in healthy individuals in obese patients with type 2 diabetes.
次要结局
- Change of C-peptide(6 hours)
- Change of glucose(6 hours)
- Change of pancreatic polypeptide(6 hours)
- Change of insulin(6 hours)
- Change of glucagon(6 hours)
- Change of GLP-1(6 hours)
- Change of IL-1β(6 hours)
- Change of IL-6(6 hours)
- Change of IL-1Ra(6 hours)
- Change of TNFa(6 hours)
- change in hunger(6 hours)
- Change in autonomic function(6 hours)