Proteomics for Identification of Hyperoxia-induced Changes in Protein Expression

Hyperoxia Clinical Trial

Official title:

Proteomics for Identification of Hyperoxia-induced Changes in Protein Expression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02553668
• Other study ID #: 15-109
• Status: Not yet recruiting
• Phase: N/A
• First received: July 9, 2015
• Last updated: September 16, 2015
• Start date: October 2015
• Est. completion date: December 2016

Study information

• Verified date: September 2015
• Source: University Hospital of Cologne
• Contact: Stefan Braunecker, M.D.
• Email: stefan.braunecker[@]uk-koeln.de
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

Aim of the present study is to investigate the influence of hyperoxia on the protein expression using the differential analysis of protein expression in tissues (proteomics). In the study, blood and urine samples will be collected from participants who undergo a short term hyperoxia using 100% oxgen for 3 hours.

Here, gel electrophoresis, protein separation and mass spectroscopy allow to identify affected proteins. Based on these results, different induction factors of proteins will be determined and then assessed using a bioinformatic network analysis regarding the cellular influence.

Description:

Oxygen is necessary to sustain human life and is used for energy production by oxidation in the mitochondria. Application of oxygen not only increases saturation in the patient's blood, but also has various secondary effects. It is therefore used to treat diseases that impairs body's ability to take up and use oxygen. But even healthy people can suffer from hypoxia when they ascend to high altitude. Here, altitude sickness can lead to potentially fatal complications such as high altitude cerebral edema or high altitude pulmonary edema. Since hypoxia can have disastrous consequences, hyperoxia is often tolerated in many pre- and in-hospital situations.

Whereas the effects of hypoxia are well studied, especially publications in the last decade have led to a new perspective on oxygen application. Besides pathophysiological changes as the peripheral vasoconstriction or reduction of contractility, especially changes on cellular level seem to be of great importance. Here, oxidative stress and change of protein synthesis in various organ are focus of current studies.

The differential analysis of protein expression in tissues (proteomics) is an important approach for better understanding of the negative effects of hyperoxia. Especially for patients with long-term high oxygen demand the knowledge of cellular changes during hyperoxia can result in new therapeutic approaches and a reduction in the rate of complications.

In the present molecular biology study urine and blood samples of healthy volunteers will be collected at specified times after short-term exposure to oxygen. These samples will be analyzed after the study using the differential analysis of protein expression. The aim of this study is to investigate the effects of oxygen on the cell functions by analyzing and subsequent bioinformatic processing of differentially regulated proteins in the blood and urine.

After checking the inclusion and exclusion criteria biometric data of the test persons are collected.

Before short-term hyperoxia a sample collection of blood and urine will be performed. Here the participants are taken 5 ml of venous blood from the cephalic vein under sterile conditions. To obtain the urine sample spontaneous urine of participants is used. The samples are immediately centrifuged and flash frozen at -80°C. In order to exclude impairment of the lung prior to the short-term hyperoxia a pulmonary function test is carried out by using a hand spirometer.

To induce hyperoxia subjects inhale 100% oxygen for 3 hours through a face mask.

After carrying out the short term hyperoxia the follow up phase takes place. In this phase blood and urine samples from the subjects will be obtained directly after the hyperoxia (T0), on day 1 (T1), day 3 (T3), day 7 (T7), day 14 (T14), day 21 (T21) and day 28 (T28) after oxygen exposure. All samples will be centrifuged immediately after collection and flash frozen at -80 ° C. To exclude hyperoxia-induced lung impairments, a spirometry is performed during the follow up.

After the samples of all subjects were collected the analysis of the samples will be carried out using Proteomics.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) 1

• >18 years

• < 50 years

Exclusion Criteria:

• American Society of Anesthesiologists (ASA) > 1

• pregnant

• <18 years

• > 50 years

• frequent or recent drug intake

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hyperoxia

Intervention

Drug:
• Oxygen (FiO2 1,0)
Participants will inhale Oxygen (FiO2 1,0) via Facemask for 3 hours.

Device:
• Facemask

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital of Cologne

References & Publications (2)

Hinkelbein J, Feldmann RE Jr, Kalenka A. Time-dependent alterations of cerebral proteins following short-term normobaric hyperoxia. Mol Cell Biochem. 2010 Jun;339(1-2):9-21. doi: 10.1007/s11010-009-0365-1. Epub 2010 Jan 5. — View Citation

Spelten O, Wetsch WA, Wrettos G, Kalenka A, Hinkelbein J. Response of rat lung tissue to short-term hyperoxia: a proteomic approach. Mol Cell Biochem. 2013 Nov;383(1-2):231-42. doi: 10.1007/s11010-013-1771-y. Epub 2013 Aug 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Comparison of proteomics changes before and after short-term hyperoxia		4 weeks	No
Secondary	Spirometry Results: Forced vital capacity (FVC) [L]	Spirometry will be used as a measure of safety to rule out adverse events of oxygen to the lung.	2 days	Yes
Secondary	Spirometry Results: Forced expiratory volume at one second (FEV1) [L]	Spirometry will be used as a measure of safety to rule out adverse events of oxygen to the lung.	2 days	Yes
Secondary	Spirometry Results: Forced expiratory flow (FEF25-75) [L/s]	Spirometry will be used as a measure of safety to rule out adverse events of oxygen to the lung.	2 days	Yes
Secondary	Spirometry Results: Peak expiratory flow (PEF) [L/s]	Spirometry will be used as a measure of safety to rule out adverse events of oxygen to the lung.	2 days	Yes
Secondary	Vital parameter: Respiratory rate (RR) [1/min]	Vital parameters will be used as a measure of safety to rule out adverse events of oxygen to the vascular system.	3 hours	Yes
Secondary	Vital parameter: Heart rate (HR) [1/min]	Vital parameters will be used as a measure of safety to rule out adverse events of oxygen to the vascular system.	3 hours	Yes
Secondary	Vital parameter: Blood pressure (BP) [mmHg]	Vital parameters will be used as a measure of safety to rule out adverse events of oxygen to the vascular system.	3 hours	Yes
Secondary	Vital parameter: Oxygen saturation (SpO2) [%]	Vital parameters will be used as a measure of safety to rule out adverse events of oxygen to the vascular system.	3 hours	Yes