Ignite Creation Date:
2025-12-25 @ 2:10 AM
Ignite Modification Date:
2026-01-03 @ 11:47 PM
Study NCT ID:
NCT01700660
Status:
COMPLETED
Last Update Posted:
2016-01-26
First Post:
2012-10-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Reperfusion-induced Self-antigen Excretion Following Major Liver Surgery
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Organization:
Study Overview
Official Title:
Reperfusion-induced Self-antigen Excretion Following Major Liver Surgery
Status:
COMPLETED
Status Verified Date:
2016-01
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:
RISE
Brief Summary:
Major liver surgery often requires the surgeon to temporarily halt the afferent blood flow in order to prevent excessive blood loss. However, this predisposes the liver to a detrimental inflammatory response once the circulation is restored. Altogether, the effects that result from this temporary withdrawal of blood are known as ischemia and reperfusion (I/R) injury, and the extent to which this occurs determines the functional outcome of the liver after surgery.
Recently, it has become clear that (over)activation of the immune system forms the mainstay of I/R injury in the liver. More importantly, it has been shown in animal models that self-antigens, which are normal cellular constituents that become immunogenic mediators following their release from dying cells, are involved in the earliest stages of I/R injury of the liver. Clinical data on the release self-antigens in I/R injury are however scarce to date. Therefore, the aim of this study is to investigate the release of self-antigens in patients that undergo a major liver resection with or without withdrawal of the liver's blood flow. Also, the results will be correlated to genes involved in the inflammatory response as well as clinical parameters for liver damage and function.
Recently, it has become clear that (over)activation of the immune system forms the mainstay of I/R injury in the liver. More importantly, it has been shown in animal models that self-antigens, which are normal cellular constituents that become immunogenic mediators following their release from dying cells, are involved in the earliest stages of I/R injury of the liver. Clinical data on the release self-antigens in I/R injury are however scarce to date. Therefore, the aim of this study is to investigate the release of self-antigens in patients that undergo a major liver resection with or without withdrawal of the liver's blood flow. Also, the results will be correlated to genes involved in the inflammatory response as well as clinical parameters for liver damage and function.
Detailed Description:
Rationale
Major liver surgery often requires the surgeon to temporarily halt the afferent blood flow in order to prevent excessive blood loss. Vascular inflow occlusion (VIO) however predisposes the liver to a detrimental inflammatory response once the circulation is restored. Altogether, the ramifications that result from this temporary withdrawal of oxygen supply are known as ischemia and reperfusion (I/R) injury, and the extent to which this occurs determines the functional outcome of the liver after surgery. Recently, it has become clear that (over)activation of the immune system forms the mainstay of hepatic I/R injury. More importantly, it has been shown in animal models that endogenous self-antigens, known as damage-associated molecular patterns (DAMPs), are released from stressed liver cells in the earliest stages of reperfusion and, as such, form the most proximal triggers of hepatic I/R injury. Clinical data on DAMP release following hepatic I/R are however scarce to date. Therefore, the aim of this study is to investigate DAMP release in patients that undergo a major liver resection with or without VIO and to correlate the results to the expression of acute- phase inflammatory response genes and routine clinical parameters for hepatocellular damage.
Objective
To investigate the release of damage-associated molecular patterns (DAMPs) following major hepatic resection with or without VIO and to correlate the outcomes to the acute inflammatory response and clinical parameters for hepatocellular damage.
Study design
The study is designed as an observational study. Because the decision to apply VIO is often made during surgery, patients will be allocated to a group postoperatively. Therefore, the inclusion of subjects in this study will continue until the calculated sample size of 15 patients has been reached in each group.
Study population
Eligible patients for participation in this study are those diagnosed with a malignant or benign hepatic tumor that are scheduled to undergo major hepatectomy (resection of ≥3 segments).
Main study parameters/endpoints
The primary endpoint of this study is defined as the effect of I/R on the release of DAMPs, measured in the systemic circulation. Secondary parameters constitute the expression of acute inflammatory response genes, AST, ALT, total bilirubin, and INR.
Major liver surgery often requires the surgeon to temporarily halt the afferent blood flow in order to prevent excessive blood loss. Vascular inflow occlusion (VIO) however predisposes the liver to a detrimental inflammatory response once the circulation is restored. Altogether, the ramifications that result from this temporary withdrawal of oxygen supply are known as ischemia and reperfusion (I/R) injury, and the extent to which this occurs determines the functional outcome of the liver after surgery. Recently, it has become clear that (over)activation of the immune system forms the mainstay of hepatic I/R injury. More importantly, it has been shown in animal models that endogenous self-antigens, known as damage-associated molecular patterns (DAMPs), are released from stressed liver cells in the earliest stages of reperfusion and, as such, form the most proximal triggers of hepatic I/R injury. Clinical data on DAMP release following hepatic I/R are however scarce to date. Therefore, the aim of this study is to investigate DAMP release in patients that undergo a major liver resection with or without VIO and to correlate the results to the expression of acute- phase inflammatory response genes and routine clinical parameters for hepatocellular damage.
Objective
To investigate the release of damage-associated molecular patterns (DAMPs) following major hepatic resection with or without VIO and to correlate the outcomes to the acute inflammatory response and clinical parameters for hepatocellular damage.
Study design
The study is designed as an observational study. Because the decision to apply VIO is often made during surgery, patients will be allocated to a group postoperatively. Therefore, the inclusion of subjects in this study will continue until the calculated sample size of 15 patients has been reached in each group.
Study population
Eligible patients for participation in this study are those diagnosed with a malignant or benign hepatic tumor that are scheduled to undergo major hepatectomy (resection of ≥3 segments).
Main study parameters/endpoints
The primary endpoint of this study is defined as the effect of I/R on the release of DAMPs, measured in the systemic circulation. Secondary parameters constitute the expression of acute inflammatory response genes, AST, ALT, total bilirubin, and INR.
Study Oversight
Has Oversight DMC:
False
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NL41737.018.12 | OTHER | Central Committee on Research involving Human Subjects, the Netherlands | View |