A New Model of Acute Febrile Disease - Combining Endotoxemia, Immobilisation and Fasting in Healthy Young Males.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- insulin sensitivity
研究概览
简要总结
The investigators want to establish a new model of acute febrile disease by mimicking the conditions seen in hospitalized patients in regards to inflammation, immobilisation and fasting. In this new model of disease, healthy young adults will be given lipopolysaccharide (LPS) to induce endotoxemia and inflammation/fever and then fast and bedrest for 36 hours. Glucose, fat and protein metabolism will be investigated using clamp technique and tracer methodology together with intracellular signalling pathway activation in muscle and fat biopsies. This new model of disease will later be used in another study to investigate different protein supplement´s effect on muscle waste during acute febrile disease.
详细描述
The investigators want to establish a new model of acute febrile disease by mimicking the conditions seen in hospitalized patients in regards to inflammation, immobilisation and fasting. In this new model of disease, healthy young adults will be given lipopolysaccharide (LPS) to induce endotoxemia and inflammation on study day 1 and then fast and bedrest for 36 hours (Study day 2). Glucose, fat and protein metabolism will be investigated using clamp technique and tracer methodology together with intracellular signalling pathway activation in muscle and fat biopsies. This new model of disease will later be used in another study to investigate different protein supplement´s effect on muscle waste during acute febrile disease.
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
- None
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •20 < BMI < 30
- •20 < Age < 40 years
- •Written consent prior to trial
排除标准
- •Participation in trials using ionized radiation a year prior to this trial.
- •Comprehensive x-ray examinations in the study period.
- •In case of immobilization of an extremity, the extremity should be fully re- habilitated and this should be stated by a physician or physiotherapist. The test subject's word for this will be sufficient.
- •Allergies to eggs or soy oil.
- •Diseases: Diabetes, epilepsy, ongoing infectious disease, immunodeficiency, heart disease, dysregulated hypertension.
研究组 & 干预措施
"LPS, 36 hour immobilization and fast"
Interventions:
Test subjects undergo 48 hour exercise restriction and overnight fast.
Study day 1:
- LPS (1 ng/kg) will be administered. Test subjects will fast and bedrest for the rest of the study period.
Study day 2:
- 3 hour Basal period: Continued fast and bedrest. Phenylalanine, tyrosine, carbamide, glucose and palmitate tracers are infused. Muscle and fat biopsies are taken from m. vastus lateralis and stomach.
- 3 hour hyperinsulinemic euglycemic clamp period with muscle and fat biopsies.
Study day 3:
- Blood sample.
干预措施: LPS, 36 hour immobilization and fast (Other)
"Control"
Test subjects undergo overnight fast. No exercise restrictions.
- 3 hour Basal period: Continued fast and bedrest. Phenylalanine, tyrosine, carbamide, glucose and palmitate tracers are infused. Muscle and fat biopsies are taken from m. vastus lateralis and stomach.
- 3 hour hyperinsulinemic euglycemic clamp period with muscle and fat biopsies.
结局指标
主要结局
insulin sensitivity
时间窗: After a 3 hour clamp
Measured by hyperinsulinemic euglycemic clamp technique
次要结局
- Protein metabolism(measured at baseline and after 3 hours of clamp)
- ketone body metabolic changes(measured at baseline and after 3 hours of clamp)
- inflammation(measurements over 36 hours)
- Intracellular signalling pathway activation(measured at baseline and after 3 hours of clamp)
- Hormonal changes(measured at baseline and after 3 hours of clamp)
- CD163(0, 24 and 48 hours after LPS exposure)
- Energy expenditure(measured at baseline and after 3 hours of clamp for 15 minutes)
- Glucose metabolism(measured at baseline and after 3 hours of clamp)
- Urea balance(measured at baseline and after 3 hours of clamp)
- Glucose uptake by the forearm(measured at baseline and after 3 hours of clamp)
- Fat metabolism(measured at baseline and after 3 hours of clamp)