EndotoxemiaVECTORNCT00785018
In Vivo Effects of C1-esterase Inhibitor on the Innate Immune Response During Human Endotoxemia
A study testing C1-esterase inhibitor and Endotoxin administration in people with Endotoxemia and Inflammation, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Excessive inflammation is associated with tissue damage caused by over-activation of the innate immune system. This can range from mild disease to extreme conditions such as multiple organ failure (MOF). Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Endotoxemia, Inflammation, Multi Organ Dysfunction Syndrome
- What is being tested?
- C1-esterase inhibitor and Endotoxin administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Nov 2008to Aug 2009
- Phase
- Interventional
- 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 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male volunteers (18-35 years old)
Who cannot join
- Relevant medical history
- Drug-, nicotine-, alcohol abuses
- Tendency towards fainting
- Hyper- or hypotension
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, 6500HB
About this study
Excessive inflammation is associated with tissue damage caused by over-activation of the innate immune system. This can range from mild disease to extreme conditions such as multiple organ failure (MOF). In marked contrast to adaptive immunity which is very sensitive to immune modulators such as steroids, the innate immune system cannot be sufficiently targeted by currently available anti-inflammatory drugs.
We hypothesize that C1-esterase inhibitor can modulate the innate immune response.
In this study, human endotoxemia will be used as a model for inflammation. Subjects will, additionally to endotoxin, receive C1 esterase inhibitor or placebo. Blood will be sampled to determine the levels of markers of the innate immune response.
Read the detailed description
Rationale:
There is an unmet need for novel therapeutic agents focused on the complications caused by acute and excessive activation of the innate immune response after injury. As this activation responds poorly to currently used therapy including inhaled steroids novel agents need to be tested, developed or applied. C1INH comprises a potential important target drug for antagonism of the excessive activation of the innate immune response during acute inflammation seen after injury. This might be achieved by inhibiting the redistribution and homing of cells to inflammatory tissues.
Before going to a clinical trial in injured human subjects we want to perform a pilot study in healthy volunteers to exploit the "human endotoxemia model". The human endotoxemia model permits elucidation of key players in this pro-inflammatory response in humans in vivo, therefore serving as a useful tool to investigate potential novel therapeutic strategies in a standardized setting. The model bears striking resemblance to LPS models in animals. These latter studies have shown that C1INH protects from neutrophil mediated disease [1-4]. Together with the finding that C1INH has been shown to be safe in the treatment of humans, we propose to use this protein in the treatment of neutrophil driven acute inflammation such as seen after injury.
Objectives:
Primary objective: The primary objective of the study is to determine the effect of C1INH on systemic activation of the innate immune response induced by LPS challenge. This response will be objectivised by measurement of enhanced TNF-α levels 90 min after LPS challenge.
Secondary Objective(s): The secondary objective of the study is to determine the effect of C1INH on redistribution of neutrophils in the human endotoxemia model.
Study design: Double-blind placebo-controlled randomized intervention study in healthy human volunteers during experimental endotoxemia.
Study population: Non-smoking healthy male volunteers, age 18-35 yrs Intervention: Subjects will receive C1INH in a dose of 100 U/kg (n=10) or placebo (n=10) 30 min after LPS administration. Pre-hydration will be performed by infusion of 1.5 L 2.5% glucose/0.45% saline solution in 1 hour before LPS administration. LPS derived from E coli O:113 will be injected (2 ng/kg iv., infusion rate 1 minute).
Main study parameters/endpoints: The main study parameter is the concentration of circulating cytokines after LPS in the absence or presence of C1INH. Secondary study parameters include the influence of C1INH on the redistribution pattern of neutrophils and neutrophil phenotypes.
- Conditions
- Endotoxemia, Inflammation, Multi Organ Dysfunction Syndrome
- Being tested
- C1-esterase inhibitor, Endotoxin administration
- Keywords
- Endotoxin, C1-inhibitor, Inflammation, Sepsis, Multi organ dysfunction syndrome, Complement activation
- Medical subject headings
- Endotoxemia, Inflammation, Angioedemas, Hereditary, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1-esterase inhibitorDrug
C1-esterase inhibitor 100 U/kg infusion over 30 minutes.
Endotoxin administrationDrug
2 ng/kg E. coli reference endotoxin 11:H 10:K negative intravenously
| Study group | Role | What they receive |
|---|---|---|
| C1-esterase inhibitor | Active comparator | Endotoxin 2ng/kg followed by C1- esterase inhibitor 100 U/kg infusion Receives: Drug: C1-esterase inhibitor; Drug: Endotoxin administration |
| Placebo | Placebo comparator | Endotoxin 2ng/kg followed by saline 0.9%(placebo) infusion Receives: Drug: Endotoxin administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytokines and other markers of Inflammation
Measured: 24 hrs after LPS administration
Neutrophil redistribution and phenotype
Measured: 24 hours after LPS administration
C1-inhibitor and complement concentration and activity
Measured: 24 hours after LPS administration
Hemodynamic response
Measured: 24 hours after LPS administration
Markers of Renal Injury
Measured: 24 hours after LPS administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionDec 2008
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndotoxemiaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Peter Pickkers, MD, PhD, Principal investigator, Radboud University Nijmegen Medical Centre, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00785018
- Sponsor's protocol ID
- VECTOR study 2008/197
- Acronym
- VECTOR
- Status last verified
- May 2009
- First submitted
- 4 Nov 2008
- Last updated
- 22 Apr 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- In Vivo Effects of C1-esterase Inhibitor on the Innate Immune Response During Human Endotoxemia
- ClinicalTrials.gov ID
- NCT00785018
- Acronym / sponsor ID
- VECTOR / VECTOR study 2008/197
- Conditions
- Endotoxemia, Inflammation, Multi Organ Dysfunction Syndrome
- Keywords
- Endotoxin, C1-inhibitor, Inflammation, Sepsis, Multi organ dysfunction syndrome, Complement activation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Nov 2008
- Primary completion
- Dec 2008 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 5 Nov 2008 (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.
Excessive inflammation is associated with tissue damage caused by over-activation of the innate immune system. This can range from mild disease to extreme conditions such as multiple organ failure (MOF). In marked contrast to adaptive immunity which is very sensitive to immune modulators such as steroids, the innate immune system cannot be sufficiently targeted by currently available anti-inflammatory drugs.
We hypothesize that C1-esterase inhibitor can modulate the innate immune response.
In this study, human endotoxemia will be used as a model for inflammation. Subjects will, additionally to endotoxin, receive C1 esterase inhibitor or placebo. Blood will be sampled to determine the levels of markers of the innate immune response.
Detailed description
Rationale:
There is an unmet need for novel therapeutic agents focused on the complications caused by acute and excessive activation of the innate immune response after injury. As this activation responds poorly to currently used therapy including inhaled steroids novel agents need to be tested, developed or applied. C1INH comprises a potential important target drug for antagonism of the excessive activation of the innate immune response during acute inflammation seen after injury. This might be achieved by inhibiting the redistribution and homing of cells to inflammatory tissues.
Before going to a clinical trial in injured human subjects we want to perform a pilot study in healthy volunteers to exploit the "human endotoxemia model". The human endotoxemia model permits elucidation of key players in this pro-inflammatory response in humans in vivo, therefore serving as a useful tool to investigate potential novel therapeutic strategies in a standardized setting. The model bears striking resemblance to LPS models in animals. These latter studies have shown that C1INH protects from neutrophil mediated disease [1-4]. Together with the finding that C1INH has been shown to be safe in the treatment of humans, we propose to use this protein in the treatment of neutrophil driven acute inflammation such as seen after injury.
Objectives:
Primary objective: The primary objective of the study is to determine the effect of C1INH on systemic activation of the innate immune response induced by LPS challenge. This response will be objectivised by measurement of enhanced TNF-α levels 90 min after LPS challenge.
Secondary Objective(s): The secondary objective of the study is to determine the effect of C1INH on redistribution of neutrophils in the human endotoxemia model.
Study design: Double-blind placebo-controlled randomized intervention study in healthy human volunteers during experimental endotoxemia.
Study population: Non-smoking healthy male volunteers, age 18-35 yrs Intervention: Subjects will receive C1INH in a dose of 100 U/kg (n=10) or placebo (n=10) 30 min after LPS administration. Pre-hydration will be performed by infusion of 1.5 L 2.5% glucose/0.45% saline solution in 1 hour before LPS administration. LPS derived from E coli O:113 will be injected (2 ng/kg iv., infusion rate 1 minute).
Main study parameters/endpoints: The main study parameter is the concentration of circulating cytokines after LPS in the absence or presence of C1INH. Secondary study parameters include the influence of C1INH on the redistribution pattern of neutrophils and neutrophil phenotypes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| C1-esterase inhibitor | Active comparator | Drug: C1-esterase inhibitor, Drug: Endotoxin administrationEndotoxin 2ng/kg followed by C1- esterase inhibitor 100 U/kg infusion |
| Placebo | Placebo comparator | Drug: Endotoxin administrationEndotoxin 2ng/kg followed by saline 0.9%(placebo) infusion |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy male volunteers (18-35 years old)
Key exclusion criteria (4 listed)
- Relevant medical history
- Drug-, nicotine-, alcohol abuses
- Tendency towards fainting
- Hyper- or hypotension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C1-esterase inhibitorC1-esterase inhibitor 100 U/kg infusion over 30 minutes. | Drug | C1-esterase inhibitor |
| Endotoxin administration2 ng/kg E. coli reference endotoxin 11:H 10:K negative intravenously | Drug | C1-esterase inhibitor, Placebo |
Primary outcome
Cytokines and other markers of Inflammation
Time frame: 24 hrs after LPS administration
Neutrophil redistribution and phenotype
Time frame: 24 hours after LPS administration
C1-inhibitor and complement concentration and activity
Time frame: 24 hours after LPS administration
Hemodynamic response
Time frame: 24 hours after LPS administration
Markers of Renal Injury
Time frame: 24 hours after LPS administration
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 22 Apr 2011.
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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.
Peter Pickkers, MD, PhD principal investigator
Radboud University Nijmegen Medical Centre, The Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing C1-esterase inhibitor and Endotoxin administration in people with Endotoxemia and Inflammation, run by Radboud University Medical Center 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 1 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 22 Apr 2011. 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. Some participants in this study may receive a placebo. 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?
Cytokines and other markers of Inflammation (time frame: 24 hrs after LPS administration). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Apr 2011.