EndotoxemiaPhase 1NCT00184990
Effect of Selective iNOS Inhibition During Human Endotoxemia
A Phase 1 study testing Aminoguanidine and endotoxin in people with Endotoxemia, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Sepsis or endotoxemia is manifested by hypotension, resistance to vasopressors, myocardial depression,and altered organ blood flow distribution. The mechanisms underlying the cardiovascular dysfunction during sepsis are complex; however, they are partially mediated by an uncontrolled production of NO by inducible NO… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Endotoxemia
- What is being tested?
- Aminoguanidine and endotoxin
- How many people
- 7 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2005to Sep 2005
- Phase
- Phase 1
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers
Who cannot join
- tendency towards fainting
- alcohol abuse
- nicotine abuse
- drugs abuse
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6500HB
About this study
Sepsis or endotoxemia is manifested by hypotension, resistance to vasopressors, myocardial depression,and altered organ blood flow distribution. The mechanisms underlying the cardiovascular dysfunction during sepsis are complex; however, they are partially mediated by an uncontrolled production of NO by inducible NO synthase (iNOS).Control subjects received 2 ng/kg E. coli endotoxin, whereas the active intervention group received endotoxin in the presence of selective iNOS-inhibitor aminoguanidine. Hemodynamics, vascular responses to norepinephrine, acetylcholine and sodium nitroprusside, as well as circulating cytokines and other mediators of inflammation were measured. We tested the hypothesis that inhibition of NO-synthesis prevented the LPS-mediated insensitivity to noradrenalin and endothelial-dependent vasorelaxation. Furthermore, we tested whether NO participates in occurrence of the endotoxin tolerance in humans by using the iNOS inhibitor aminoguanidine on healthy volunteers with endotoxemia. At 0; 2 and 4 hours after the LPS challenge whole blood was stimulated with five TLR agonists in vitro and pro- and anti-inflammatory cytokines were measured.
- Conditions
- Endotoxemia
- Being tested
- Aminoguanidine, endotoxin
- Keywords
- Endotoxemia, Aminoguanidine
- Medical subject headings
- Endotoxemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AminoguanidineDrug
endotoxinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemodynamics
Measured: 24 hrs after LPS administration
Markers of Inflammation
Measured: 24 hrs after LPS administration
Cytokines
Measured: 24 hrs after LPS administration
Markers of Renal Injury
Measured: 24 hrs after LPS administration
Inducible NO synthase expression
Measured: 24 hrs after LPS administration
NO-metabolites
Measured: 24 hrs after LPS administration
Mediators of Vascular reactivity
Measured: 24 hrs after LPS administration
Sensitivity to norepinephrine
Measured: 24 hrs after LPS administration
Endothelial-dependent vasorelaxation
Measured: 24 hrs 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 posted16 Sep 2005 (estimated)
- Study startJan 2005
- Primary completionSep 2005
- Study completionSep 2005
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 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Peter Pickkers, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00184990
- Sponsor's protocol ID
- PP01
- Status last verified
- Apr 2008
- First submitted
- 12 Sep 2005
- Last updated
- 15 Apr 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Selective iNOS Inhibition During Human Endotoxemia
- ClinicalTrials.gov ID
- NCT00184990
- Acronym / sponsor ID
- PP01
- Conditions
- Endotoxemia
- Keywords
- Endotoxemia, Aminoguanidine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jan 2005
- Primary completion
- Sep 2005 (actual)
- Study completion
- Sep 2005 (actual)
- First posted
- 16 Sep 2005 (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.
Sepsis or endotoxemia is manifested by hypotension, resistance to vasopressors, myocardial depression,and altered organ blood flow distribution. The mechanisms underlying the cardiovascular dysfunction during sepsis are complex; however, they are partially mediated by an uncontrolled production of NO by inducible NO synthase (iNOS).Control subjects received 2 ng/kg E. coli endotoxin, whereas the active intervention group received endotoxin in the presence of selective iNOS-inhibitor aminoguanidine. Hemodynamics, vascular responses to norepinephrine, acetylcholine and sodium nitroprusside, as well as circulating cytokines and other mediators of inflammation were measured. We tested the hypothesis that inhibition of NO-synthesis prevented the LPS-mediated insensitivity to noradrenalin and endothelial-dependent vasorelaxation. Furthermore, we tested whether NO participates in occurrence of the endotoxin tolerance in humans by using the iNOS inhibitor aminoguanidine on healthy volunteers with endotoxemia. At 0; 2 and 4 hours after the LPS challenge whole blood was stimulated with five TLR agonists in vitro and pro- and anti-inflammatory cytokines were measured.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy volunteers
Key exclusion criteria (4 listed)
- tendency towards fainting
- alcohol abuse
- nicotine abuse
- drugs abuse
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 |
|---|---|---|
| Aminoguanidine | Drug | – |
| endotoxin | Drug | – |
Primary outcome
Hemodynamics
Time frame: 24 hrs after LPS administration
Markers of Inflammation
Time frame: 24 hrs after LPS administration
Cytokines
Time frame: 24 hrs after LPS administration
Markers of Renal Injury
Time frame: 24 hrs after LPS administration
Inducible NO synthase expression
Time frame: 24 hrs after LPS administration
NO-metabolites
Time frame: 24 hrs after LPS administration
Mediators of Vascular reactivity
Time frame: 24 hrs after LPS administration
Sensitivity to norepinephrine
Time frame: 24 hrs after LPS administration
Endothelial-dependent vasorelaxation
Time frame: 24 hrs 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 15 Apr 2008.
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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, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aminoguanidine and endotoxin in people with Endotoxemia, 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 15 Apr 2008. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Hemodynamics (time frame: 24 hrs after LPS administration). The study lists 9 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 15 Apr 2008.