E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Possible future indications: inflammatory conditions in general, autoimmune diseases |
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E.1.1.1 | Medical condition in easily understood language |
The investigated therapy could prove to be beneficial in a variety of conditions associated with inflammation, for example auto-immune diseases |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age>18 and <35 yrs
Male
Healthy |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | 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 |
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E.5.2 | Secondary end point(s) |
- HIF-1α protein and mRNA and aHIF mRNA in circulating leukocytes
- Circulating cytokines (including, but not limited to IL-6, IL-10, and IL1RA)
- ROS
- Phagocyting capacity of leukocytes
- Cytokine responses by leukocytes ex vivo stimulated with various inflammatory stimuli
- Core body temperature
- Hemodynamic parameters (heart rate, blood pressure)
- Respiratory frequency
- Arterial blood gas parameters
- Leukocyte counts and differentiation
- Illness score
- Adenosine metabolism
- Cognitive function tests
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |