Effects of oxygen blood level on inflammatio

Phase 1

• Conditions: Possible future indications: inflammatory conditions in general, autoimmune diseases; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2013-002390-21-NL
• Lead Sponsor: Radboud University Nijmegen Medical Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-08-20
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

Age>18 and <35 yrs
Male
Healthy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 pulmonary diseases, including 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

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of the study is to determine the effects of hyperoxia and hypoxia compared to normoxia in the human endotoxemia model on kinetics of plasma TNF alpha in healthy volunteers;Secondary Objective: Secondary objectives are to determine the effects of hyperoxia and hypoxia on HIF-1a protein, HIF-1a mRNA and aHIF mRNA expression in circulating leukocytes, the induction of ROS, the effects on phagocytosis, basic hemodynamic and ventilatory parameters;Primary end point(s): The primary objective of the study is to determine the effects of hypoerxia and hypoxia, comapred with normoxia, in human endotoxemia on plasma TNF-a;Timepoint(s) of evaluation of this end point: at -60, 0, 60, 90, 120, 240, 360 and 480 minutes and 24 hours after LPS administration

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -HIF-1a protein and mRNA and aHIF mRNA in circulating leukocytes<br>-Circulating cytokines (including, but not limited to IL-6, IL-10, and IL1RA)<br>-ROS <br>-Phagocyting capacity of leukocytes <br>-Cytokine responses by leukocytes ex vivo stimulated with various inflammatory stimuli<br>-Core body temperature<br>-Hemodynamic parameters (heart rate, blood pressure)<br>-Respiratory frequency <br>-Arterial blood gas parameters<br>-Leukocyte counts and differentiation<br>-Illness score<br>-Adenosine metabolism<br>-Cognitive function tests <br>;Timepoint(s) of evaluation of this end point: at -60, 0, 60, 90, 120, 240, 360 and 480 minutes and 24 hours after LPS administration