Effects of Oxygen Status on Hypoxia Inducible Factor 1-α and Inflammation. A Pilot Proof of Principle Study.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Hypoxia Inducible Factor 1 alpha in circulating leukocytes
研究概览
简要总结
It has been shown in in vitro and animal models that hypoxia can have pro-inflammatory effects and hyperoxia can have anti-inflammatory effects. The pro-inflammatory effect could be the result of activation of Hypoxia Inducible Factor, a transcription factor that is known to activate many cell systems aimed at cell survival, including the inflammatory response. The anti-inflammatory effects of hyperoxia could be the annihilation of Hypoxia Inducible Factor, but also a decrease in inflammation due to oxygen toxicity resulting in a decrease in clearance of pathogens. These effects have been sparsely studied in humans. Therefore, we hypothesize that hypoxia results in an increase in Hypoxia Inducible Factor in circulating leukocytes and increases inflammatory reactions, whereas hyperoxia decreases these reactions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 and ≤35 yrs
排除标准
- •Use of any medication
- •History, signs or symptoms of cardiovascular disease
- •History of atrial or ventricular arrhythmia
- •(Family) history of myocardial infarction or stroke under the age of 65 years
- •Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block
- •Hypertension (defined as RR systolic > 160 or RR diastolic > 90 mmHg)
- •Hypotension (defined as RR systolic < 100 or RR diastolic < 50 mmHg)
- •Renal impairment (defined as plasma creatinine >120 μmol/l)
- •Liver enzyme abnormalities alkaline phosphatase>230 U/L and/or ALT>90 U/L
- •Medical history of any obvious disease associated with immune deficiency
- •CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxemia day
- •Participation in a drug trial or donation of blood 3 months prior to the experiment
- •Pre-existent lung disease or asthma
- •Use of recreational drugs within 21 days prior to experiment day
- •Visit to altitude >1500m within 4 weeks prior to the experiment
- •Air travel with flight time over 3 hours within 4 weeks prior to the experiment
- •History of acute mountain sickness
- •Recent hospital admission or surgery with general anaesthesia (<3 months)
- •Claustrophobia
- •Feelings of discomfort during a 10 minute test wearing the transparent respiratory helmet at the screening visit
结局指标
主要结局
Hypoxia Inducible Factor 1 alpha in circulating leukocytes
时间窗: 24 hours
Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymphocytes and monocytes as measured with flow cytometry
次要结局
- ventilatory response(24 hours)
- adenosine metabolism(24 hours)
- Hepcidin and iron parameters(24 hours)
- subjective symptoms(24 hours)
- high sensitive troponin(24 hours)
- oxygen saturation and PaO2(24 hours)
- iFABP(24 hours)
- Brain specific proteins(24 hours)
- endocan(24 hours)
- Phagocytic function of circulating leukocytes(24 hours)
- cognitive function(24 hours)
- Neutrophil function(24 hours)
- Reactive Oxygen Species in circulating leukocytes(24 hours)
- circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA)(24 hours)
- body temperature(24 hours)
- VEGF(24 hours)
- cytokine production after ex vivo stimulation of leukocytes(24 hours)
- catecholamines(24 hours)
- adrenomedullin(24 hours)
- Hemodynamic parameters(24 hours)
- alkaline phosphatase(24 hours)
- EPO(24 hours)
- Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes(24 hours)
- Heart rate variability(24 hours)
研究者
Peter Pickkers
Prof. dr. P. Pickkers
Radboud University Medical Center