Determining the Fingerprint of Endotoxin Tolerance

NCT06801873 | Completed DMC

• 2 other identifiers: NL68166.091.182018-4983
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Endotoxemia; Sepsis; Systemic Inflammation; Immunosuppresion

Keywords

Systemic inflammation; Human endotoxemia; Sepsis; Immunosuppression; endotoxin tolerance; Genomics; Transcriptomics

Outcome Measures

Primary Outcomes (3)

• SNPs

  Single-nucleotide polymorphisms (SNPs)

  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

  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).

  From 1 hour before the first LPS challenge until 6 hours after the second LPS challenge

Secondary Outcomes (2)

• Sex hormones

  1 hour before the first LPS administration

• Gender

  Enrollment

Study Arms (1)

LPS

EXPERIMENTAL

All healthy subjects (male/female) are challenged with endotoxin (LPS) twice.

Other: Endotoxin (E. coli O:113, Reference Endotoxin)

Interventions

Endotoxin (E. coli O:113, Reference Endotoxin) OTHER

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

LPS

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent
• Age ≥18 and ≤35 yrs
• Male
• Healthy (as confirmed by medical history, examination, ECG, blood sampling)

You may not qualify if:

• 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)
• 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)

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Intensive Care Medicine Deparmtent

Nijmegen, Gelderland, 6500HB, Netherlands

Location

MeSH Terms

Conditions

Endotoxemia; Sepsis

Interventions

Endotoxins; Lipopolysaccharides

Condition Hierarchy (Ancestors)

Bacteremia; Infections; Toxemia; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Bacterial Toxins; Toxins, Biological; Biological Factors; Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 30, 2025
• Study Start: May 27, 2019
• Primary Completion: February 20, 2020
• Study Completion: August 20, 2020
• Last Updated: February 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Access Criteria: RNA-seq data for this study will become available on GEO database.

Locations

NL (1)