Influence on Erythropoetin-level by Xenon

Study Overview
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Brief Summary
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The purpose of this study is to analyze the effect of xenon-inhalation on erythropoetin-level in blood of healthy volunteers and to determine the efficient time of inhalation. Hypothesis: Xenon-inhalation enhances erythropoetin-levels in blood

Detailed Description
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Xenon-gas is an approved anesthetic by the EMEA and is used for a balanced anesthesia in combination with opioids for adults with a american society of anesthesiology classification ASA ≤ III. Several clinical and pre-clinical studies have shown a positive effect of xenon on several organ functions such as in brain, kidneys and heart. In two studies, an enhanced expression of hypoxia inducible factor-1α (HIF-1α) could be shown in animal kidneys and kidney cells. Interestingly, HIF-1α leads to an enhanced formation of erythropoetin (EPO). This might result in an enhanced oxygen transport capacity and an enhanced oxygen-level after xenon-treatment. Aim of the project is to analyze the effect of xenon-inhalation on circulating erythropoetin-level in blood of healthy volunteers in a randomized controlled pilot study. Besides, other positive stimulating factors for erythropoiesis (such as HIFa stabilizing factors) and growth factors (such as fibroblast growth factors (FGFs), hepatocyte growth factor (HGF), mechano growth factors (MGFs), platelet-derived growth factors (PDGFs), vascular endothelial growth factors (VEGFs)) shall be analyzed.

Official Title
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Xenon-inhalation: Elimination of Xenon and Its Effect on Erythropoetin Levels in Blood of Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Xenon pro Anaesthesia 100 % (V/V)
* Drug: Aer medicinalis Linde 100%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects Age: > 18 years legally competent to sign without any known medical condition or medication prescribed at the University Hospital RWTH Aachen, Germany Persons that are able and willing to understand and follow the instructions of the study personnel Signed informed consent Exclusion Criteria: Smoker, alcoholic or person who regularly consumes drugs or medication Persons with a medical condition that is contraindicated with the planned treatment Known hypersensitivity against xenon Persons not legally competent to sign Simultaneous participation at any other trial Blood-loss due to trauma during the period of the study or 2 months previous Blood donation during the period of the study or 2 months previous

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10min Xenon 15%, FiO2 75%<br>10 minutes of 15 % xenon-inhalation (with 75 % FiO2) | Drug: Xenon pro Anaesthesia 100 % (V/V)<br>* Xenon-gas inhalation of indicated concentrations during indicated time<br>* Other names: licence number: 56582.00.00;|
| Experimental: 10min Xenon 30%, FiO2 60%<br>10 minutes of 30 % xenon-inhalation (with 60 % FiO2) | Drug: Xenon pro Anaesthesia 100 % (V/V)<br>* Xenon-gas inhalation of indicated concentrations during indicated time<br>* Other names: licence number: 56582.00.00;|
| Experimental: 30min Xenon 15%, FiO2 75%<br>30 minutes of 15 % xenon-inhalation (with 75 % FiO2) | Drug: Xenon pro Anaesthesia 100 % (V/V)<br>* Xenon-gas inhalation of indicated concentrations during indicated time<br>* Other names: licence number: 56582.00.00;|
| Experimental: 30min Xenon 30%, FiO2 60%<br>30 minutes of 30 % xenon-inhalation (with 60 % FiO2) | Drug: Xenon pro Anaesthesia 100 % (V/V)<br>* Xenon-gas inhalation of indicated concentrations during indicated time<br>* Other names: licence number: 56582.00.00;|
| Experimental: 45min Xenon 15%, FiO2 75%<br>45 minutes of 15 % xenon-inhalation (with 75 % FiO2) | Drug: Xenon pro Anaesthesia 100 % (V/V)<br>* Xenon-gas inhalation of indicated concentrations during indicated time<br>* Other names: licence number: 56582.00.00;|
| Experimental: 45min Xenon 30%, FiO2 60%<br>45 minutes of 30 % xenon-inhalation (with 60 % FiO2) | Drug: Xenon pro Anaesthesia 100 % (V/V)<br>* Xenon-gas inhalation of indicated concentrations during indicated time<br>* Other names: licence number: 56582.00.00;|
| Experimental: 90min Xenon 15%, FiO2 75%<br>90 minutes of 15 % xenon-inhalation (with 75 % FiO2) | Drug: Xenon pro Anaesthesia 100 % (V/V)<br>* Xenon-gas inhalation of indicated concentrations during indicated time<br>* Other names: licence number: 56582.00.00;|
| Experimental: 90min Xenon 30%, FiO2 60%<br>90 minutes of 30 % xenon-inhalation (with 60 % FiO2) | Drug: Xenon pro Anaesthesia 100 % (V/V)<br>* Xenon-gas inhalation of indicated concentrations during indicated time<br>* Other names: licence number: 56582.00.00;|
| Placebo Comparator: 10min air medicinalis, FiO2 75%<br>10 minutes of air medicinalis (with 75 % FiO2) | Drug: Aer medicinalis Linde 100%<br> <br> * Other names: ATC-Code: V03AN05;|
| Placebo Comparator: 10min air medicinalis, FiO2 60%<br>10 minutes of air medicinalis inhalation (with 60 % FiO2) | Drug: Aer medicinalis Linde 100%<br> <br> * Other names: ATC-Code: V03AN05;|
| Placebo Comparator: 30min air medicinalis, FiO2 75%<br>30 minutes of air medicinalis inhalation (with 75 % FiO2) | Drug: Aer medicinalis Linde 100%<br> <br> * Other names: ATC-Code: V03AN05;|
| Placebo Comparator: 30min air medicinalis, FiO2 60%<br>30 minutes of air medicinalis inhalation (with 60 % FiO2) | Drug: Aer medicinalis Linde 100%<br> <br> * Other names: ATC-Code: V03AN05;|
| Placebo Comparator: 45min air medicinalis, FiO2 75%<br>45 minutes of air medicinalis inhalation (with 75 % FiO2) | Drug: Aer medicinalis Linde 100%<br> <br> * Other names: ATC-Code: V03AN05;|
| Placebo Comparator: 45min air medicinalis, FiO2 60%<br>45 minutes of air medicinalis inhalation (with 60 % FiO2) | Drug: Aer medicinalis Linde 100%<br> <br> * Other names: ATC-Code: V03AN05;|
| Placebo Comparator: 90min air medicinalis, FiO2 75%<br>90 minutes of air medicinalis inhalation (with 75 % FiO2) | Drug: Aer medicinalis Linde 100%<br> <br> * Other names: ATC-Code: V03AN05;|
| Placebo Comparator: 90min air medicinalis, FiO2 60%<br>90 minutes of air medicinalis inhalation (with 60 % FiO2) | Drug: Aer medicinalis Linde 100%<br> <br> * Other names: ATC-Code: V03AN05;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in erythropoetin-level in blood of healthy volunteers up to 216 hrs after the first of three xenon applications in total | Change from baseline in erythropoetin-level in blood of healthy volunteers up to 216 hrs after the first of three xenon applications in total. Timepoints of measurement: Before each inhalation, Directly after the first inhalation, 2 hrs after the first inhalation, 4 hrs after the first inhalation, 8 hrs after the first inhalation, 22-24 hrs after each inhalation, 46-48 hrs after each inhalation, 70-72 hrs after the last inhalation, 94-96 hrs after the last inhalation, 118-120 hrs after the last inhalation | up to 216 hrs after first xenon-application | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First-order elimination of xenon after xenon-inhalation in blood and exhalation air by mass-spectroscopy | Timepoints of measurement: Before each inhalation, Directly after the first inhalation, 2 hrs after the first inhalation, 4 hrs after the first inhalation, 8 hrs after the first inhalation, 22-24 hrs after each inhalation, 46-48 hrs after each inhalation, 70-72 hrs after the last inhalation, 94-96 hrs after the last inhalation, 118-120 hrs after the last inhalation | up to 216 hrs after the first xenon-application | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xenon-inhalation, Erythropoetin, Pharmakokinetic, Pharmacodynamic, Hemodynamic parameters, Inflammatory parameters, Growth factors, Oxidative stress parameters