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

Hypoxia Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01889823
• Other study ID #: OX1
• Status: Completed
• Phase: Phase 1
• First received: June 26, 2013
• Last updated: March 24, 2015
• Start date: June 2013
• Est. completion date: December 2014

Study information

• Verified date: March 2015
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Independent Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Age =18 and =35 yrs

• Male

• Healthy

Exclusion Criteria:

• Use of any medication

• Smoking

• 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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hyperoxia
• Hypoxia

Intervention

Other:
• Hypoxia
Subjects will be breathing an individualized mix of nitrogen and room air titrated to an oxygen saturation of 80-85%.
• Hyperoxia
Subjects will be breathing 100% oxygen

Locations

Country	Name	City	State
Netherlands	Intensive Care Medicine, Radboud University Nijmegen Medical Centre	Nijmegen	Nijmegen, Gelderland

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hypoxia Inducible Factor 1 alpha in circulating leukocytes	Hypoxia Inducible Factor 1 alpha in circulating neutrophils, lymphocytes and monocytes as measured with flow cytometry	24 hours	No
Secondary	Hypoxia Inducible Factor mRNA and anti Hypoxia Inducible Factor mRNA in circulating leukocytes		24 hours	No
Secondary	Reactive Oxygen Species in circulating leukocytes	ROS in circulating leukocytes, subclassified in neutrophils and monocytes	24 hours	No
Secondary	Phagocytic function of circulating leukocytes		24 hours	No
Secondary	cytokine production after ex vivo stimulation of leukocytes		24 hours	No
Secondary	circulating cytokines (including but not limited to IL-6, IL-10, IL-1RA)		24 hours	No
Secondary	Hemodynamic parameters	Blood pressure, heart frequency, cardiac output measurement	24 hours	No
Secondary	ventilatory response	Measures of ventilation: respiratory rate, blood gas changes	24 hours	No
Secondary	adenosine metabolism	urine and plasma adenosine,adenosine receptor mRNA, purines	24 hours	No
Secondary	alkaline phosphatase		24 hours	No
Secondary	cognitive function	neuropsychologic assessment of cognitive function	24 hours	No
Secondary	Hepcidin and iron parameters		24 hours	No
Secondary	catecholamines	adrenaline, noradrenaline and dopamine	24 hours	No
Secondary	Neutrophil function		24 hours	No
Secondary	body temperature		24 hours	No
Secondary	oxygen saturation and PaO2		24 hours	No
Secondary	subjective symptoms		24 hours	No
Secondary	high sensitive troponin		24 hours	No
Secondary	iFABP		24 hours	No
Secondary	Brain specific proteins		24 hours	No
Secondary	endocan		24 hours	No
Secondary	adrenomedullin		24 hours	No
Secondary	EPO		24 hours	No
Secondary	VEGF		24 hours	No
Secondary	Heart rate variability		24 hours	No