An interventional study of Endotoxin (E. coli O:113, Reference Endotoxin) in Endotoxemia, Sepsis and Systemic Inflammation, sponsored by Radboud University Medical Center. Completed at 1 site in Netherlands. Open to participants aged 18 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-02-07.
Sponsored by Radboud University Medical Center · Not applicable, Interventional, and Other
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
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.
81 studies on the registry are indexed under Endotoxemia; 7 are open to participants now.
This study's enrollment of 110 is above the median of 31 across 70 interventional studies indexed under Endotoxemia.
Browse Endotoxemia studies →Radboud University Medical Center is the lead sponsor of 986 studies on the registry; 136 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All healthy subjects (male/female) are challenged with endotoxin (LPS) twice.
Other: Endotoxin (E. coli O:113, Reference Endotoxin)
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.
Also known as: LPS, Lipopolysaccharide
SNPs
Single-nucleotide polymorphisms (SNPs)
Time frame: 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
Time frame: 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).
Time frame: From 1 hour before the first LPS challenge until 6 hours after the second LPS challenge
Sex hormones
Blood concentrations of estradiol, estrone and testosterone (in pmol/L) and testosteron (in nmol/L)
Time frame: 1 hour before the first LPS administration
Gender
Time frame: Enrollment
Plan to share: Yes — Omics data such as SNP/transcriptional/metabolomics data will be shared.
Supporting information: Statistical analysis plan, Analytic code
Access criteria: RNA-seq data for this study will become available on GEO database.
No publications or documents are linked to this record.
This study is completed, as verified in Jan 2025. You cannot join it, but the record below documents what was studied.
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