Clinical Trial: Effects of Oxygen Status on Hypoxia Inducible Factor 1-α and Inflammation. A Pilot Proof of Principle Study.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title:

Brief Summary: 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.

Detailed Summary:
Sponsor: Radboud University

Current Primary Outcome: Hypoxia Inducible Factor 1 alpha in circulating leukocytes [ Time Frame: 24 hours ]

Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymphocytes and monocytes as measured with flow cytometry


Original Primary Outcome: Hypoxia Inducible Factor 1 alpha in circulating leukocytes [ Time Frame: 24 hours ]

Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymfocytes and monocytes as measured with flow cytometry


Current Secondary Outcome:

  • Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes [ Time Frame: 24 hours ]
  • Reactive Oxygen Species in circulating leukocytes [ Time Frame: 24 hours ]
    ROS in circulating leukocytes, subclassified in neutrophils and monocytes
  • Phagocytic function of circulating leukocytes [ Time Frame: 24 hours ]
  • cytokine production after ex vivo stimulation of leukocytes [ Time Frame: 24 hours ]
  • circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA) [ Time Frame: 24 hours ]
  • Hemodynamic parameters [ Time Frame: 24 hours ]
    Blood pressure, heart frequency, cardiac output measurement
  • ventilatory response [ Time Frame: 24 hours ]
    Measures of ventilation: respiratory rate, blood gas changes
  • adenosine metabolism [ Time Frame: 24 hours ]
    urine and plasma adenosine,adenosine receptor mRNA, purines
  • alkaline phosphatase [ Time Frame: 24 hours ]
  • cognitive function [ Time Frame: 24 hours ]
    neuropsychologic assessment of cognitive function
  • Hepcidin and iron parameters [ Time Frame: 24 hours ]
  • catecholamines [ Time Frame: 24 hours ]
    adrenaline, noradrenaline and dopamine
  • Neutrophil function [ Time Frame: 24 hours ]
  • body temperature [ Time Frame: 24 hours ]
  • oxygen saturation and PaO2 [ Time Frame: 24 hours ]
  • subjective symptoms [ Time Frame: 24 hours ]
  • high sensitive troponin [ Time Frame: 24 hours ]
  • iFABP [ Time Frame: 24 hours ]
  • Brain specific proteins [ Time Frame: 24 hours ]
  • endocan [ Time Frame: 24 hours ]
  • adrenomedullin [ Time Frame: 24 hours ]
  • EPO [ Time Frame: 24 hours ]
  • VEGF [ Time Frame: 24 hours ]
  • Heart rate variability [ Time Frame: 24 hours ]


Original Secondary Outcome:

  • Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes [ Time Frame: 24 hours ]
  • Reactive Oxygen Species in circulating leukocytes [ Time Frame: 24 hours ]
    ROS in circulating leukocytes, subclassified in neutrophils and monocytes
  • Phagocytic function of circulating leukocytes [ Time Frame: 24 hours ]
  • cytokine production after ex vivo stimulation of leukocytes [ Time Frame: 24 hours ]
  • circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA) [ Time Frame: 24 hours ]
  • Hemodynamic parameters [ Time Frame: 24 hours ]
    Blood pressure, heart frequency, cardiac output measurement
  • ventilatory response [ Time Frame: 24 hours ]
    Measures of ventilation: respiratory rate, blood gas changes
  • adenosine metabolism [ Time Frame: 24 hours ]
    urine and plasma adenosine,adenosine receptor mRNA, purines
  • alkaline phosphatase [ Time Frame: 24 hours ]
  • cognitive function [ Time Frame: 24 hours ]
    neuropsychologic assesment of cognitive function
  • Hepcidin and iron parameters [ Time Frame: 24 hours ]
  • catecholamines [ Time Frame: 24 hours ]
    adrenaline, noradrenaline and dopamine
  • Neutrophil function [ Time Frame: 24 hours ]
  • body temperature [ Time Frame: 24 hours ]
  • oxygen saturation and PaO2 [ Time Frame: 24 hours ]
  • subjective symptoms [ Time Frame: 24 hours ]
  • high sensitive troponine [ Time Frame: 24 hours ]
  • iFABP [ Time Frame: 24 hours ]
  • Brain specific proteins [ Time Frame: 24 hours ]
  • endocan [ Time Frame: 24 hours ]
  • adrenomedullin [ Time Frame: 24 hours ]
  • EPO [ Time Frame: 24 hours ]
  • VEGF [ Time Frame: 24 hours ]
  • Heart rate variability [ Time Frame: 24 hours ]


Information By: Radboud University

Dates:
Date Received: June 26, 2013
Date Started: June 2013
Date Completion:
Last Updated: March 24, 2015
Last Verified: March 2015