Cerebral Hemodynamic Effects of Oxygen and Antioxidants
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Change in circulating microparticle concentration (total MPs - EV)
研究概览
简要总结
This study is called CHE-OX-ANT (Cerebral Hemodynamic Effects of Oxygen and Antioxidants). It is a single-center, academic research project led by the Department of Intensive Care at Erasme Hospital (Université Libre de Bruxelles).
The study focuses on understanding how the brain and blood vessels react when a person breathes pure oxygen and how these effects may be influenced by giving vitamin C, an antioxidant. Oxygen is one of the most common treatments in hospitals. While it can be life-saving, too much oxygen may sometimes cause harmful effects, such as oxidative stress (an imbalance between damaging molecules called free radicals and the body's defenses). Antioxidants like vitamin C may help counteract these effects.
The goal of the study is to examine how a short period of high oxygen (30 minutes of 100% oxygen through a mask) affects cerebral hemodynamics, microcirculation, microperfusion, blood markers (levels of oxidative stress, antioxidant activity, and microparticles).
The study will also test whether giving vitamin C beforehand changes these responses compared to a placebo (saline solution).
Each volunteer will participate in two sessions, one week apart. Before each session, participants will receive either vitamin C (given intravenously) or a placebo (saline). They will not know which one they receive.
Then, they will breathe 100% oxygen for 30 minutes through a facial mask. Measurements will be taken at three times: before oxygen (t0), just after oxygen (t1), and 1 hour later (t2). These include: ultrasound of the brain's blood flow (transcranial Doppler), measurements of skin perfusion and blood samplings.
详细描述
Oxygen therapy is widely used in hospitals and critical care, but excessive oxygen levels (hyperoxemia) can have both beneficial and harmful effects. In the brain, high oxygen may improve oxygen delivery, but it can also trigger oxidative stress, inflammation, and vascular dysfunction, potentially worsening outcomes. Antioxidants, such as vitamin C (ascorbic acid), may counteract these harmful effects by neutralizing reactive oxygen species and restoring redox balance. The CHE-OX-ANT study aims to investigate the physiological effects of a short normobaric hyperoxic stimulus (30 minutes of 100% oxygen breathing) in healthy volunteers, with and without prior antioxidant administration. The primary focus is on oxidative stress markers and microparticle production, while secondary objectives include effects on cerebral blood flow, sublingual microcirculation, and skin perfusion.
This is a prospective, interventional, single-center, randomized, single-blind, placebo-controlled physiological trial conducted at Erasme Hospital, Brussels. Each subject will serve as their own control, undergoing two study sessions one week apart. The study will recruit 10-15 healthy adult volunteers. Eligible participants must be >18 years old, in good health, with no cardiovascular, neurological, hematological, or immunological disease. Exclusion criteria include smoking, pregnancy, BMI >25, or contraindications to oxygen or vitamin
At each session, participants will receive one of two randomized pre-treatments, administered intravenously 30-60 minutes before oxygen exposure:
Vitamin C group: 1-3 g ascorbic acid in 500 mL saline infused over 20 minutes. Placebo group: 500 mL of saline infused over 20 minutes. Following this, participants will breathe 100% oxygen for 30 minutes through a reservoir mask. Measurements will be obtained at three timepoints: baseline (t0), immediately after oxygen (t1), and 2 hours post-exposure (t2).
Cerebral hemodynamics: Transcranial Doppler ultrasonography. Skin perfusion: laser Doppler or infrared techniques. Blood samples: venous and arterial blood for oxidative stress, antioxidant status, microparticles, and arterial blood gas analysis.
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
- Single (Participant)
盲法说明
Participants are blinded to the intervention (placebo vs. vitamin C infusion). Investigators and care providers are not blinded due to the nature of the procedures.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Otherwise healthy, without known pathologies in the cardiovascular, neurological, immunological, renal hematological, or vascular systems.
排除标准
- •Pregnant women
- •BMI > 25
- •Any reason to avoid vit. C
- •Any reason to avoid breathing oxygen at high doses
研究组 & 干预措施
Vitamin C Pre-Treatment + Oxygen
Participants receive an intravenous infusion of 2 g ascorbic acid (vitamin C - ascorbic acid) diluted in 250 mL saline over 20 minutes, 30-60 minutes before breathing 100% oxygen for 30 minutes through a reservoir mask. Measurements are performed at baseline, immediately after oxygen, and 1 hour later (cerebral blood flow by transcranial Doppler and skin perfusion, blood pressure, arterial blood gases, oxidative stress markers, and microparticles).
干预措施: Vitamin C (Ascorbic Acid) (Drug)
Vitamin C Pre-Treatment + Oxygen
Participants receive an intravenous infusion of 2 g ascorbic acid (vitamin C - ascorbic acid) diluted in 250 mL saline over 20 minutes, 30-60 minutes before breathing 100% oxygen for 30 minutes through a reservoir mask. Measurements are performed at baseline, immediately after oxygen, and 1 hour later (cerebral blood flow by transcranial Doppler and skin perfusion, blood pressure, arterial blood gases, oxidative stress markers, and microparticles).
干预措施: Oxygen (Other)
Placebo Pre-Treatment + Oxygen
Participants receive an intravenous infusion of 250 mL saline (placebo) over 20 minutes, 30-60 minutes before breathing 100% oxygen for 30 minutes through a reservoir mask. Measurements are performed at baseline, immediately after oxygen, and 1 hour later (cerebral blood flow by transcranial Doppler and skin microperfusion, blood pressure, arterial blood gases, oxidative stress markers, and microparticles).
干预措施: Oxygen (Other)
结局指标
主要结局
Change in circulating microparticle concentration (total MPs - EV)
时间窗: t0 = baseline (before infusion/oxygen administration) t1 = immediately after 30 minutes of 100% O₂ t2 = 1 hour after the end of exposure (post-exposure)
A composite extracellular vesicle (MPs - EV) outcome reflecting brain and cerebral endothelial responses to hyperoxia, quantified in plasma by flow cytometry. The composite index will be derived from the standardized (z-score) change from baseline of the following EV subpopulations: GFAP-positive EVs (astrocyte-derived EVs) Aquaporin-4 (AQP4)-positive EVs (astrocyte/BBB-related EVs) TMEM119-positive EVs (microglia-related EVs) VE-cadherin (CD144)-positive EVs (endothelial junction-related EVs) CD62E (E-selectin)-positive EVs (endothelial activation-related EVs) Each EV subpopulation will be quantified as concentration (EVs/µL plasma). For each participant and time point, individual EV concentrations will be normalized (z-transformed) and combined into a single composite EV score by averaging the standardized values. The reported metric will be the within-participant change in the composite EV score from baseline (Δt1-t0 and Δt2-t0).
Change in oxidative stress and antioxidant status
时间窗: t0 = baseline (before infusion/oxygen administration) t1 = immediately after 30 minutes of 100% O₂ t2 = 1 hour after the end of exposure (post-exposure)
A composite biochemical outcome reflecting systemic oxidative stress and antioxidant balance in response to hyperoxia and vitamin C administration. The composite index will be derived from the standardized (z-score) change from baseline of the concentrations of the erythrocyte biomarker of antioxidant defense in mg/dL. For each participant and time point, biomarker values will be normalized (z-transformed) and combined
次要结局
- Change in cerebral hemodynamics and autoregulation composite index(t0 = baseline (before infusion/oxygen administration) t1 = immediately after 30 minutes of 100% O₂ t2 = 1 hour after the end of exposure (post-exposure))
- Change in skin perfusion(t0 = baseline (before infusion/oxygen administration) t1 = immediately after 30 minutes of 100% O₂ t2 = 1 hour after the end of exposure (post-exposure))
研究者
Fabio Taccone
Head of Department of Intensive Care
Erasme University Hospital