Effects of Hyperoxia Induced Pulmonary Inflammation and Organ Injury in a Human in Vivo Model
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Bronchoalveolar lavage Interleukin-8 (IL-8) concentration
研究概览
简要总结
Oxygen is the most commonly administered therapy in critical illness. Accumulating evidence suggests that patients often achieve supra-physiological levels of oxygenation in the critical care environment. Furthermore, hyperoxia related complications following cardiac arrest, myocardial infarction and stroke have also been reported. The underlying mechanisms of hyperoxia mediated injury remain poorly understood and there are currently no human in vivo studies exploring the relationship between hyperoxia and direct pulmonary injury and inflammation as well as distant organ injury.
The current trial is a mechanistic study designed to evaluate the effects of prolonged administration of high-flow oxygen (hyperoxia) on pulmonary and systemic inflammation. The study is a randomised, double-blind, placebo-controlled trial of high-flow nasal oxygen therapy versus matching placebo (synthetic medical air). We will also incorporate a model of acute lung injury induced by inhaled endotoxin (LPS) in healthy human volunteers. Healthy volunteers will undergo bronchoalveolar lavage (BAL) at 6 hours post-intervention to enable measurement of pulmonary and systemic markers of inflammation, oxidative stress and cellular injury.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy non-smoking subjects less than 45 years of age and BMI < 29 kg/m²
排除标准
- •Age < 18 years
- •On concomitant medications including over the counter medications excluding oral contraception and paracetamol
- •Previous adverse reactions to LPS, lignocaine or sedative agents
- •Pregnant or Breast-Feeding
- •Participation in a clinical trial of an investigational medicinal product within 30 days
- •Consent declined
- •History of asthma or other respiratory conditions
- •Smoking/ e cigarette use
- •Marijuana use or other inhaled products with or without nicotine in the last 3 months
- •Alcohol abuse, as defined by the Alcohol Use Disorders Identification Test (AUDIT)
- •Subjects with history of prior conventional cigarette (> 100 cigarettes lifetime and smoking within 6 months) or electronic cigarette use.
研究组 & 干预措施
Synthetic medical air
Synthetic medical air will be administered using high-flow nasal cannula delivery system.
干预措施: medical air (Drug)
Liquid medical oxygen
Liquid medical oxygen will be administered using high-flow nasal cannula delivery system.
干预措施: Liquid oxygen (Drug)
结局指标
主要结局
Bronchoalveolar lavage Interleukin-8 (IL-8) concentration
时间窗: 6 hours post-intervention
To determine the effects of hyperoxia on alveolar inflammatory response
次要结局
- Bronchoalveolar lavage oxidised low density lipoprotein (oxLDL)(6 hours post-intervention)
- Bronchoalveolar lavage cytokines including but not limited to tumour necrosis factor alpha, IL-1 beta and IL-6(6 hours post-intervention)
- Bronchoalveolar lavage total protein(6 hours post-intervention)
- Bronchoalveolar lavage 4-hydroxy-2-nonenal (4-HNE)(6 hours post-intervention)
- Plasma advanced glycation end products (AGE)(6 and 24 hours post-intervention)
- Plasma oxidised low density lipoprotein (oxLDL)(6 and 24 hours post-intervention)
- Plasma 4-hydroxy-2-nonenal (4-HNE)(6 and 24 hours post-intervention)
- Bronchoalveolar lavage proteases and anti-proteases including but not limited to Matrix Metalloproteinases (MMP-2, MMP-8, MMP-9 and MMP-11), Tissue Inhibitors of Metalloproteinase (TIMPs 1-2) and neutrophil elastase(6 hours post-intervention)
- Bronchoalveolar lavage white cell differential counts (total cell count, neutrophils, macrophages and lymphocytes)(6 hours post-intervention)
- Bronchoalveolar lavage soluble programmed cell death receptor (SP-D)(6 hours post-intervention)
- Plasma cytokines including but not limited to IL-8, tumour necrosis factor alpha, IL-1 beta and IL-6(6 and 24 hours post-intervention)
- Bronchoalveolar lavage receptor for advanced glycation end-products (RAGE)(6 hours post-intervention)