Endotoxin & Cytokines. Do Protein Loss and Metabolic Effects Depend on CNS Activation of Stress Hormones or on Local Mechanisms in Muscle and Fat?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Acute metabolic effects of endotoxin and cytokine TNF-α (Study 2)
研究概览
简要总结
Main objective :
The purpose of this study is to prove that the effects of bacterial endotoxin and cytokine TNF-α, on protein loss, fatty acid release, and glucose metabolism depend on two mechanisms:
- Direct local effects in muscle tissue.
- Activation of the hypothalamo-pituitary axis and a stress-hormone response
Study protocols:
- Acute metabolic effects of TNF-α(Beromun, Boehringer-Ingelheim Germany) vs placebo perfused into the femoral artery of the leg in 8 healthy subjects.
- Acute metabolic effects of
- placebo(saline)
- endotoxin(US standard reference E.Coli, endotoxin)
- TNF-α(Beromun, Boehringer-Ingelheim Germany) given systemically
- in 8 patients with hypopituitarism(to block stress hormone release) and in 8 healthy subjects all studied thrice.
详细描述
PURPOSE:
Knowledge about the effects of bacterial endotoxin and cytokines (and inflammation in general) in humans on protein, glucose and lipid metabolism and intracellular signalling in muscle and fat is sporadic and it is uncertain whether endotoxin and cytokines act directly in fat and muscle tissue or indirectly via central nervous system (CNS) mediated stress hormone release.
The investigators hypothesize that the metabolic effects of endotoxin and cytokine TNF-α, including protein loss, fatty acid release and decreased glucose uptake depend on two mechanisms:
- Direct local effects in muscle tissue (Study protocol 1)
- Activation of the hypothalamo-pituitary axis and generalized stress hormone response (Study protocol 2)
METHODOLOGY:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •19 < BMI < 28
- •18 ≤ Age ≤ 50
- •Inclusion Criteria
- •20 < BMI < 30
- •Age > 25
排除标准
- 未提供
结局指标
主要结局
Acute metabolic effects of endotoxin and cytokine TNF-α (Study 2)
时间窗: 4 hours
During a hyperinsulinaemic euglycaemic clamp. Acute metabolic effects: Glucose metabolism was quantified with raw arterio-venous differences and 3H3-Glucose tracer. Lactate was quantified with raw arterio-venous differences. Lipid metabolism was quantified with \[9,10-3H\]-Palmitate tracer and amino acid metabolism with 15N-Phenylalanine tracer and 13C-Urea tracer.
Acute metabolic effects of cytokine TNF-α (Study 1)
时间窗: 3 hours
During a basal period. Acute metabolic effects: Glucose and lactate were quantified with raw arterio-venous differences; lipid metabolism was quantified with \[9,10-3H\]-palmitate and amino acid metabolism with 15N-phenylalanine.
次要结局
- Intracellular insulin signaling, growth hormone signalling and inflammatory signalling pathways.(30 min.)
研究者
Ermina Bosnjak
Medical Doctor, PhD student
Aarhus University Hospital