Warm Hepatic Ischemia-reperfusion InjuryRISENCT01700660
Reperfusion-induced Self-antigen Excretion Following Major Liver Surgery
An observational study of Warm Hepatic Ischemia-reperfusion Injury, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Warm Hepatic Ischemia-reperfusion Injury
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2012to Dec 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients diagnosed with a malignant or benign hepatic tumor that are scheduled for a liver resection.
Who may be able to join
- Patients scheduled to undergo a major liver resection for a benign or malignant hepatic tumor
- Signed informed consent obtained prior to any study-specific procedure
- ASA classification I-III
Who cannot join
- VIO <20 min
- ASA classification IV/V
- Emergency operations
- Pregnancy or breast feeding
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Center
Amsterdam, North Holland, 1105 AZ
About this study
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.
Read the 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.
- Conditions
- Warm Hepatic Ischemia-reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| VIO | Patients operated under VIO. | |
| Control | Patients operated without VIO. |
What is being measured
The primary outcome is the main question the study is designed to answer.
DAMPs in systemic circulation
Plasma DAMP levels will be determined perioperatively.
Measured: 8 hours
Secondary outcomes (3)
Up regulation of acute inflammatory response genes
Up regulation of acute inflammatory response genes will be determined in liver biopsy tissue (acquired intraoperatively) by means of qPCR.
Measured: 1 hour
Parenchymal damage
Measured as plasma ALT and AST.
Measured: 8 hours
Liver function
Assessed by means of total bilirubin levels and prothrombin time.
Measured: 8 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startOct 2012
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Warm Hepatic Ischemia-reperfusion InjuryStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Megan J. Reiniers, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Thomas M. van Gulik, MD, PhD, Study director, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)Megan J. Reiniers, MSc, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01700660
- Sponsor's protocol ID
- 2012_238
- Other IDs
- NL41737.018.12
- Acronym
- RISE
- Status last verified
- Jan 2016
- First submitted
- 3 Oct 2012
- Last updated
- 26 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
van Golen RF, van Gulik TM, Heger M. The sterile immune response during hepatic ischemia/reperfusion. Cytokine Growth Factor Rev. 2012 Jun;23(3):69-84. doi: 10.1016/j.cytogfr.2012.04.006. Epub 2012 May 17.
PubMed 22609105
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reperfusion-induced Self-antigen Excretion Following Major Liver Surgery
- ClinicalTrials.gov ID
- NCT01700660
- Acronym / sponsor ID
- RISE / 2012_238
- Conditions
- Warm Hepatic Ischemia-reperfusion Injury
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Oct 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 4 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VIO | – | –Patients operated under VIO. |
| Control | – | –Patients operated without VIO. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with a malignant or benign hepatic tumor that are scheduled for a liver resection.
Key inclusion criteria (3 listed)
- Patients scheduled to undergo a major liver resection for a benign or malignant hepatic tumor
- Signed informed consent obtained prior to any study-specific procedure
- ASA classification I-III
Key exclusion criteria (4 listed)
- VIO <20 min
- ASA classification IV/V
- Emergency operations
- Pregnancy or breast feeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
DAMPs in systemic circulation
Time frame: 8 hours
Plasma DAMP levels will be determined perioperatively.
3 secondary outcomes
Up regulation of acute inflammatory response genes
Time frame: 1 hour
Parenchymal damage
Time frame: 8 hours
Liver function
Time frame: 8 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2016.
- Background: PubMed 22609105van Golen RF, van Gulik TM, Heger M. The sterile immune response during hepatic ischemia/reperfusion. Cytokine Growth Factor Rev. 2012 Jun;23(3):69-84. doi: 10.1016/j.cytogfr.2012.04.006. Epub 2012 May 17.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas M. van Gulik, MD, PhD study director
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Megan J. Reiniers, MSc principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Warm Hepatic Ischemia-reperfusion Injury, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DAMPs in systemic circulation (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01700660, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2016; AzTrials last refreshed its copy on 7 Nov 2026.