Ignite Creation Date:
2024-05-06 @ 3:25 AM
Last Modification Date:
2024-10-26 @ 11:33 AM
Study NCT ID:
NCT02286544
Status:
COMPLETED
Last Update Posted:
2017-12-11
First Post:
2014-10-27
Brief Title:
Effects of Oxygen Treatment on Mechanisms Involved in Ischemia-reperfusion Injury A Pilot Study in Healthy Volunteers
Sponsor:
Karolinska Institutet
Organization:
Karolinska Institutet
Study Overview
Official Title:
Effects of Oxygen Treatment on Mechanisms Involved in Ischemia-reperfusion Injury A Single Center Randomized Controlled Pilot Study in Healthy Volunteers
Status:
COMPLETED
Status Verified Date:
2017-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Oxygen treatment is widely used in acutely ill patients In particular oxygen treatment is routinely used in acute coronary syndrome ACS patients with suspected acute myocardial infarction and variably recommended in ACS-guidelines despite very limited data supporting a beneficial effect
Immediate re-opening of the acutely occluded infarct-related bloodvessel via primary percutaneous coronary intervention PCI is the treatment of choice to limit ischemic injury in the setting of ST-elevation ACS STE-ACS However the sudden re-initiation of blood flow achieved with primary PCI can give rise to further damage so-called reperfusion injury Ischemia and reperfusion associated myocardial injury IR-injury involves a wide range of pathological processes Vascular leakage activation of cell death programs transcriptional reprogramming no reflow phenomenon and innate and adaptive immune activation all contribute to tissue damage thereby determining the infarct size The effect of oxygen treatment on these pathological processes on the extent of IR-injury and the final infarct size in STE-ACS patients has not previously been studied
ACS is characterized by a systemic inflammation with typical elevations of soluble inflammatory markers as well as changes in white blood cells The inflammatory reaction might be considered helpful in restoring myocardial tissue structure and function but on the other hand it might worsen IR-injury by activating various pathological processes In human experimental studies Salmonella typhi vaccine has been used to create a standardized model of systemic inflammation and when administered to healthy volunteers the vaccination has not been associated with any adverse events
In an ongoing register randomized multicentre clinical trial the DETO2X Determination of role of oxygen in suspected acute myocardial infarction study the effect of oxygen on morbidity and mortality in ACS patients is being investigated In a substudy of the DETO2X-trial the investigators have planned to evaluate the effect of oxygen treatment on IR-injury in STE-ACS as assessed by biomarkers reflecting various aspects of the pathological processes involved
The presented study is an experimental pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury
Immediate re-opening of the acutely occluded infarct-related bloodvessel via primary percutaneous coronary intervention PCI is the treatment of choice to limit ischemic injury in the setting of ST-elevation ACS STE-ACS However the sudden re-initiation of blood flow achieved with primary PCI can give rise to further damage so-called reperfusion injury Ischemia and reperfusion associated myocardial injury IR-injury involves a wide range of pathological processes Vascular leakage activation of cell death programs transcriptional reprogramming no reflow phenomenon and innate and adaptive immune activation all contribute to tissue damage thereby determining the infarct size The effect of oxygen treatment on these pathological processes on the extent of IR-injury and the final infarct size in STE-ACS patients has not previously been studied
ACS is characterized by a systemic inflammation with typical elevations of soluble inflammatory markers as well as changes in white blood cells The inflammatory reaction might be considered helpful in restoring myocardial tissue structure and function but on the other hand it might worsen IR-injury by activating various pathological processes In human experimental studies Salmonella typhi vaccine has been used to create a standardized model of systemic inflammation and when administered to healthy volunteers the vaccination has not been associated with any adverse events
In an ongoing register randomized multicentre clinical trial the DETO2X Determination of role of oxygen in suspected acute myocardial infarction study the effect of oxygen on morbidity and mortality in ACS patients is being investigated In a substudy of the DETO2X-trial the investigators have planned to evaluate the effect of oxygen treatment on IR-injury in STE-ACS as assessed by biomarkers reflecting various aspects of the pathological processes involved
The presented study is an experimental pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury
Detailed Description:
HYPOTHESIS The main hypothesis is that oxygen treatment can increase oxidative stress systemic inflammation markers of apoptosis matrix metalloproteinases MMPs and their tissue inhibitor TIMPs in individuals subjected to endotoxin-induced inflammation The investigators also hypothesize that pretreatment with statins can prevent this oxygen effect
AIMS
To evaluate whether oxygen treatment can increase oxidative stress in healthy volunteers subjected to vaccine-induced inflammation
To assess the effect of oxygen treatment on plasma levels of soluble markers of apoptosis MMPs and TIMPs in healthy volunteers with vaccine-induced inflammation
To study the effect of oxygen treatment on systemic inflammatory activity and leukocyte subset distribution in healthy volunteers with vaccine-induced inflammation
To evaluate the effect of oxygen treatment on platelet aggregation in healthy volunteers with vaccine-induced inflammation
To determine whether a potential oxygen effect on these cellular- and biomarkers can be prevented by pretreatment with Atorvastatin
To serve as a pilot study and basis for power calculations for a future planned study Effects of oxygen treatment on biomarkers of reperfusion damage and infarct size in ST-elevation myocardial infarction patients undergoing primary PCI
DESIGN The present study is an experimental randomized pilot study in healthy volunteers
STUDY POPULATION The investigators intend to include 36 healthy male volunteers Females will not be included due to the potential risk of hazardous effects of Salmonella typhi vaccine and Atorvastatin to a fetus in case of pregnancy
STUDY DESIGN
At the time of inclusion all study participants will be randomised into one of three intervention groups
Group 1 Salmonella typhi vaccine Group 2 Salmonella typhi vaccine oxygen treatment Group 3 Salmonella typhi vaccine oxygen treatment Atorvastatin At 800 am on study day a peripheral venous catheter will be inserted This catheter will be used to collect blood sample during the study day In addition peripheral oxygen saturation will be measured by pulse oximetry After baseline venous blood samples have been collected all study participants will receive 05 mL of the Salmonella typhi vaccine as an intramuscular injection Typhim Vi Sanofi Pasteur MSD injection solution 25 microgram05 mL
Half an hour after vaccination is administered oxygen treatment will be initiated in group 2 and 3 at 6 Lmin via Oxymask and continued for 6 hours During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry In group 3 a single dose of Atorvastatin 80 mg will be given immediately prior to start of oxygen Venous blood samples will be collected at 3 6 and 8 hours after baseline After the 8-hour blood sampling the peripheral venous catheter will be removed and the study day ended
An experienced registered nurse and a resident or specialist in Cardiology and Internal Medicine will be present during the entire study day taking care of all study interventions collecting blood samples and register data into the case report form CRF including potential adverse events
EFFICACY OUTCOMES
To determine the effect of oxygen treatment on biomarkers of oxidative stress apoptosis matrix metalloproteinases markers of inflammation and platelet aggregation in healthy volunteers with Salmonella typhi vaccine-induced inflammation
To compare levels of these cellular- and biomarkers over time during an 8-hour study day
SUMMARY The presented study is an experimental randomized pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying to date unknown effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury As part of the DETO2X trial series this study aims to contribute essential knowledge to clarifying the role of oxygen in treatment of acute myocardial infarction
AIMS
To evaluate whether oxygen treatment can increase oxidative stress in healthy volunteers subjected to vaccine-induced inflammation
To assess the effect of oxygen treatment on plasma levels of soluble markers of apoptosis MMPs and TIMPs in healthy volunteers with vaccine-induced inflammation
To study the effect of oxygen treatment on systemic inflammatory activity and leukocyte subset distribution in healthy volunteers with vaccine-induced inflammation
To evaluate the effect of oxygen treatment on platelet aggregation in healthy volunteers with vaccine-induced inflammation
To determine whether a potential oxygen effect on these cellular- and biomarkers can be prevented by pretreatment with Atorvastatin
To serve as a pilot study and basis for power calculations for a future planned study Effects of oxygen treatment on biomarkers of reperfusion damage and infarct size in ST-elevation myocardial infarction patients undergoing primary PCI
DESIGN The present study is an experimental randomized pilot study in healthy volunteers
STUDY POPULATION The investigators intend to include 36 healthy male volunteers Females will not be included due to the potential risk of hazardous effects of Salmonella typhi vaccine and Atorvastatin to a fetus in case of pregnancy
STUDY DESIGN
At the time of inclusion all study participants will be randomised into one of three intervention groups
Group 1 Salmonella typhi vaccine Group 2 Salmonella typhi vaccine oxygen treatment Group 3 Salmonella typhi vaccine oxygen treatment Atorvastatin At 800 am on study day a peripheral venous catheter will be inserted This catheter will be used to collect blood sample during the study day In addition peripheral oxygen saturation will be measured by pulse oximetry After baseline venous blood samples have been collected all study participants will receive 05 mL of the Salmonella typhi vaccine as an intramuscular injection Typhim Vi Sanofi Pasteur MSD injection solution 25 microgram05 mL
Half an hour after vaccination is administered oxygen treatment will be initiated in group 2 and 3 at 6 Lmin via Oxymask and continued for 6 hours During oxygen treatment peripheral oxygen saturation will be measured by pulsoximetry In group 3 a single dose of Atorvastatin 80 mg will be given immediately prior to start of oxygen Venous blood samples will be collected at 3 6 and 8 hours after baseline After the 8-hour blood sampling the peripheral venous catheter will be removed and the study day ended
An experienced registered nurse and a resident or specialist in Cardiology and Internal Medicine will be present during the entire study day taking care of all study interventions collecting blood samples and register data into the case report form CRF including potential adverse events
EFFICACY OUTCOMES
To determine the effect of oxygen treatment on biomarkers of oxidative stress apoptosis matrix metalloproteinases markers of inflammation and platelet aggregation in healthy volunteers with Salmonella typhi vaccine-induced inflammation
To compare levels of these cellular- and biomarkers over time during an 8-hour study day
SUMMARY The presented study is an experimental randomized pilot study performed in healthy volunteers with a Salmonella typhi vaccine-induced inflammation with the purpose of studying to date unknown effects of oxygen treatment on biological systems involved in the pathogenesis of IR- injury As part of the DETO2X trial series this study aims to contribute essential knowledge to clarifying the role of oxygen in treatment of acute myocardial infarction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2014-002282-30 | EUDRACT_NUMBER | None | None |