Endotoxemia100LPSNCT06801873
Determining the Fingerprint of Endotoxin Tolerance
A study testing Endotoxin (E. coli O:113, Reference Endotoxin) in people with Endotoxemia and Sepsis, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
An explorative, prospective study in 100 healthy volunteers who will be challenged with endotoxin twice to identify SNPs and transcripts that are associated with the degree of endotoxin tolerance Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Endotoxemia, Sepsis, Systemic Inflammation
- What is being tested?
- Endotoxin (E. coli O:113, Reference Endotoxin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteNetherlands
- Study dates
- 27 May 2019to 20 Aug 2020
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent
- Age ≥18 and ≤35 yrs
- Male
- Healthy (as confirmed by medical history, examination, ECG, blood sampling)
Who cannot join
- Use of any medication
- Smoking
- History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema)
- Known anaphylaxis or hypersensitivity to the non-investigational products or their excipients.
- History or signs of hematological disease (bone marrow dysfunction):
- Thrombocytopenia (<150*10^9/ml) or anemia (hemoglobin < 8.0 mmol/L)
Show all 24Show fewer
- Abnormalities in leukocyte differential counts
- History, signs or symptoms of cardiovascular disease, in particular:
- Previous spontaneous vagal collapse
- History of atrial or ventricular arrhythmia
- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complete left bundle branch block
- Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
- Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
- Renal impairment (defined as plasma creatinine >120 μmol/l)
- Liver enzyme abnormalities (above 2x the upper limit of normal)
- Medical history of any disease associated with immune deficiency
- CRP > 20 mg/L, WBC > 12x109/L or < 4 x109/L, or clinically significant acute illness, including infections, within 3 weeks before labeling day
- Previous (participation in a study with) LPS administration
- Any vaccination within 3 months prior to labeling day
- Participation in a drug trial or donation of blood 3 months prior to labeling day
- Recent hospital admission or surgery with general anesthesia (<3 months to labeling day)
- Use of recreational drugs within 21 days prior to labeling day
- Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study.
- Unwillingness to be informed about potential chance findings
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Intensive Care Medicine Deparmtent
Nijmegen, Gelderland, 6500HB
About this study
An explorative, prospective study in 100 healthy volunteers who will be challenged with endotoxin twice to identify SNPs and transcripts that are associated with the degree of endotoxin tolerance
Read the detailed description
Sepsis remains the number one cause of death in the ICU and incident rates are rising. The focus of sepsis research has shifted away from the hyperinflammatory phase towards the detrimental role of immunosuppression, a phenomenon known as "sepsis-induced immunoparalysis". Because to a high level of heterogeneity and a lack of appropriate biomarkers, a much-warranted precision medicine approach is not possible. The identification of novel biomarkers for sepsis-induced immunoparalysis is also hampered by the extreme heterogeneity of the patient population. Experimental human endotoxemia is a highly standardized, controlled and reproducible model, which results in the development of endotoxin tolerance, an immunologic state capturing many hallmarks of sepsis-induced immunoparalysis. This study aims to identify genomic and transcriptomics biomarkers of endotoxin tolerance. Ultimately, this will lead to the identification of novel biomarkers for the early identification of patients who are prone to develop sepsis-induced immunoparalysis, and facilitate precision medicine for this highly vulnerable group. Primarily, the investigators aim to identify SNPs and transcripts that are associated with the degree of endotoxin tolerance. To increase the chances of success, the genomic and transcriptomic data obtained in vivo will be integrated with data obtained by a previously performed in vitro study. Secondary objectives include SNPs and transcripts associated with the inflammatory response, and epigenomic changes, metabolites, and proteins associated with the inflammatory response and the degree of endotoxin tolerance. Furthermore, the investigators will explore the role of gender and sex hormones in the inflammatory response and endotoxin tolerance, as well as the relationship between ex vivo and in vivo inflammatory responses. This is an explorative, prospective study in 100 healthy volunteers who will be challenged with endotoxin twice. The study takes place at the research unit of the department of Intensive Care Medicine of the Radboud University Medical Center, Nijmegen.
- Conditions
- Endotoxemia, Sepsis, Systemic Inflammation, Immunosuppresion
- Being tested
- Endotoxin (E. coli O:113, Reference Endotoxin)
- Keywords
- Systemic inflammation, Human endotoxemia, Sepsis, Immunosuppression, endotoxin tolerance, Genomics, Transcriptomics
- Medical subject headings
- Endotoxemia, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endotoxin (E. coli O:113, Reference Endotoxin)Other
Also called LPS, Lipopolysaccharide
Intravenous administration of 1 ng/kg (total body weight) endotoxin (Lot no. 94332B1; List Biological Laboratories, Campbell, USA). This is a non-investigational product. Endotoxin is used as challenge agent to achieve a controlled inflammatory state.
| Study group | Role | What they receive |
|---|---|---|
| LPS | Experimental | All healthy subjects (male/female) are challenged with endotoxin (LPS) twice. Receives: Other: Endotoxin (E. coli O:113, Reference Endotoxin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
SNPs
Single-nucleotide polymorphisms (SNPs)
Measured: 1 hour before the first LPS administration
Monocyte transcriptomes
Genome-wide differential mRNA expression of monocytes obtained before and 4 hours after the first endotoxin challenge
Measured: 1 hour before and 4 hours after the first LPS administration
Endotoxin tolerance
Difference in plasma cytokine concentration profiles upon the first and second endotoxin challenge (including but not limited to TNFα, IL-6, IL-8, and IL-10 all in pg/mL).
Measured: From 1 hour before the first LPS challenge until 6 hours after the second LPS challenge
Secondary outcomes (2)
Sex hormones
Blood concentrations of estradiol, estrone and testosterone (in pmol/L) and testosteron (in nmol/L)
Measured: 1 hour before the first LPS administration
Gender
Measured: Enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2025
- Study start27 May 2019
- Primary completion20 Feb 2020
- Study completion20 Aug 2020
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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This study aims to identify the genomic and transcriptomic factors linked to the development of endotoxin tolerance in vivo. To this end, all subjects will be intravenously challenged with endotoxin (2 ng/kg LPS) to evoke a transient systemic inflammatory response and subsequent development of endotoxin tolerance, which will be quantified by the response upon the second endotoxin challenge one week later. LPS is used as a challenge agent and is a non-invenstigational product, all study participants will receive the challenge.
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06801873
- Sponsor's protocol ID
- NL68166.091.18
- Other IDs
- 2018-4983
- Acronym
- 100LPS
- Status last verified
- Jan 2025
- First submitted
- 10 Jan 2025
- Last updated
- 7 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Omics data such as SNP/transcriptional/metabolomics data will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determining the Fingerprint of Endotoxin Tolerance
- ClinicalTrials.gov ID
- NCT06801873
- Acronym / sponsor ID
- 100LPS / NL68166.091.18
- Conditions
- Endotoxemia, Sepsis, Systemic Inflammation, Immunosuppresion
- Keywords
- Systemic inflammation, Human endotoxemia, Sepsis, Immunosuppression, endotoxin tolerance, Genomics, Transcriptomics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 27 May 2019 (actual)
- Primary completion
- 20 Feb 2020 (actual)
- Study completion
- 20 Aug 2020 (actual)
- First posted
- 30 Jan 2025 (actual)
- 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.
An explorative, prospective study in 100 healthy volunteers who will be challenged with endotoxin twice to identify SNPs and transcripts that are associated with the degree of endotoxin tolerance
Detailed description
Sepsis remains the number one cause of death in the ICU and incident rates are rising. The focus of sepsis research has shifted away from the hyperinflammatory phase towards the detrimental role of immunosuppression, a phenomenon known as "sepsis-induced immunoparalysis". Because to a high level of heterogeneity and a lack of appropriate biomarkers, a much-warranted precision medicine approach is not possible. The identification of novel biomarkers for sepsis-induced immunoparalysis is also hampered by the extreme heterogeneity of the patient population. Experimental human endotoxemia is a highly standardized, controlled and reproducible model, which results in the development of endotoxin tolerance, an immunologic state capturing many hallmarks of sepsis-induced immunoparalysis. This study aims to identify genomic and transcriptomics biomarkers of endotoxin tolerance. Ultimately, this will lead to the identification of novel biomarkers for the early identification of patients who are prone to develop sepsis-induced immunoparalysis, and facilitate precision medicine for this highly vulnerable group. Primarily, the investigators aim to identify SNPs and transcripts that are associated with the degree of endotoxin tolerance. To increase the chances of success, the genomic and transcriptomic data obtained in vivo will be integrated with data obtained by a previously performed in vitro study. Secondary objectives include SNPs and transcripts associated with the inflammatory response, and epigenomic changes, metabolites, and proteins associated with the inflammatory response and the degree of endotoxin tolerance. Furthermore, the investigators will explore the role of gender and sex hormones in the inflammatory response and endotoxin tolerance, as well as the relationship between ex vivo and in vivo inflammatory responses. This is an explorative, prospective study in 100 healthy volunteers who will be challenged with endotoxin twice. The study takes place at the research unit of the department of Intensive Care Medicine of the Radboud University Medical Center, Nijmegen.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study aims to identify the genomic and transcriptomic factors linked to the development of endotoxin tolerance in vivo. To this end, all subjects will be intravenously challenged with endotoxin (2 ng/kg LPS) to evoke a transient systemic inflammatory response and subsequent development of endotoxin tolerance, which will be quantified by the response upon the second endotoxin challenge one week later. LPS is used as a challenge agent and is a non-invenstigational product, all study participants will receive the challenge.
| Arm | Type | Receives |
|---|---|---|
| LPS | Experimental | Other: Endotoxin (E. coli O:113, Reference Endotoxin)All healthy subjects (male/female) are challenged with endotoxin (LPS) twice. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Written informed consent
- Age ≥18 and ≤35 yrs
- Male
- Healthy (as confirmed by medical history, examination, ECG, blood sampling)
Key exclusion criteria (24 listed)
- Use of any medication
- Smoking
- History or signs of atopic syndrome (asthma, rhinitis with medication and/or eczema)
- Known anaphylaxis or hypersensitivity to the non-investigational products or their excipients.
- History or signs of hematological disease (bone marrow dysfunction):
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 |
|---|---|---|
| Endotoxin (E. coli O:113, Reference Endotoxin)Also: LPS, LipopolysaccharideIntravenous administration of 1 ng/kg (total body weight) endotoxin (Lot no. 94332B1; List Biological Laboratories, Campbell, USA). This is a non-investigational product. Endotoxin is used as challenge agent to achieve a controlled inflammatory state. | Other | LPS |
Primary outcome
SNPs
Time frame: 1 hour before the first LPS administration
Single-nucleotide polymorphisms (SNPs)
Monocyte transcriptomes
Time frame: 1 hour before and 4 hours after the first LPS administration
Genome-wide differential mRNA expression of monocytes obtained before and 4 hours after the first endotoxin challenge
Endotoxin tolerance
Time frame: From 1 hour before the first LPS challenge until 6 hours after the second LPS challenge
Difference in plasma cytokine concentration profiles upon the first and second endotoxin challenge (including but not limited to TNFα, IL-6, IL-8, and IL-10 all in pg/mL).
2 secondary outcomes
Sex hormones
Time frame: 1 hour before the first LPS administration
Gender
Time frame: Enrollment
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 7 Feb 2025.
- Individual participant dataSharing planned: Yes. Omics data such as SNP/transcriptional/metabolomics data will be shared.
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OxiCLEAR (Oxiris Cytokines and Endotoxin Adsorption Rate) Study
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Active, not recruiting
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Endotoxin (E. coli O:113, Reference Endotoxin) in people with Endotoxemia and Sepsis, 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 4 inclusion and 24 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 7 Feb 2025. 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?
SNPs (time frame: 1 hour before the first LPS administration). The study lists 3 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 7 Feb 2025.