Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06626984
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2023-05-03
Brief Title:
Investigation of Novel and Established Therapies in a Human Intravenous Lipopolysaccharide Model of Sepsis
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Investigation of Novel and Established Therapies in a Human Intravenous Lipopolysaccharide Model of Sepsis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
INITIALISE
Brief Summary:
Sepsis is a common and life-threatening condition caused by a dysregulated host immune response to infection Given the prominent role of endothelial breakdown and dysfunction in sepsis therefore there is an urgent need to establish strategies to protect the endothelium and preserve microcirculatory function
This study is a randomised clinical study investigating intravenous fluid therapy and oral imatinib therapy in healthy human volunteers exposed to intravenous lipopolysaccharide LPS
The objective of the study is to investigate the biological effects of fluid and imatinib therapy on LPS-induced microcirculatory dysfunction
This study is a randomised clinical study investigating intravenous fluid therapy and oral imatinib therapy in healthy human volunteers exposed to intravenous lipopolysaccharide LPS
The objective of the study is to investigate the biological effects of fluid and imatinib therapy on LPS-induced microcirculatory dysfunction
Detailed Description:
The benefits of intravenous fluid administration in sepsis remain uncertain A growing body of evidence suggests that excessive fluid administration is harmful An association between a more positive fluid balance and mortality in critically ill patients has been repeatedly demonstrated Moreover emerging evidence suggests that intravenous fluid administration induces glycocalyx injury thought to be mediated by shear stress In sepsis the rapid administration of intravenous fluids is hypothesised to exacerbate glycocalyx injury capillary leak and tissue oedema formation
Recent work has highlighted the protective effects of Imatinib a tyrosine kinase inhibitor on endothelial barrier function in animal models of microcirculatory dysfunction as well as in patients with endothelial barrier dysfunction Moreover Imatinib has also been demonstrated to attenuate markers of systemic inflammation in animals with a LPS-induced lung injury model of acute respiratory distress syndrome There is therefore a growing body of evidence to support a potential therapeutic role for Imatinib in disease states involving inflammatory vascular leak
The hypothesis being tested is that
1 Intravenous fluid therapy will exacerbate the degree of vascular dysfunction and systemic inflammation observed in this model
2 Imatinib pre-treatment will attenuate the degree of vascular dysfunction and systemic inflammation observed in this model
Recent work has highlighted the protective effects of Imatinib a tyrosine kinase inhibitor on endothelial barrier function in animal models of microcirculatory dysfunction as well as in patients with endothelial barrier dysfunction Moreover Imatinib has also been demonstrated to attenuate markers of systemic inflammation in animals with a LPS-induced lung injury model of acute respiratory distress syndrome There is therefore a growing body of evidence to support a potential therapeutic role for Imatinib in disease states involving inflammatory vascular leak
The hypothesis being tested is that
1 Intravenous fluid therapy will exacerbate the degree of vascular dysfunction and systemic inflammation observed in this model
2 Imatinib pre-treatment will attenuate the degree of vascular dysfunction and systemic inflammation observed in this model
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