Determining the fingerprint of endotoxin tolerance

Determining the fingerprint of endotoxin tolerance - 100LPS study

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON48466

Enrollment

100

Registered

2019-02-04

Start date

2019-05-06

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

bloodstream infection sepsis

Interventions

This study aims to identify the genomic and transcriptomic factors linked to the development of endotoxin tolerance in vivo. To this end, subjects will be intravenously challenged with endotoxin (1

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: * Written informed consent * Age *18 and *35 yrs * Healthy (as confirmed by medical history, physical examination, electrocardiography, laboratory tests)

Exclusion criteria

Exclusion criteria: * Pregnancy (confirmed by negative result of pregnancy tests prior to both endotoxin challenges) * 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 excipi-ents. * History or signs of hematological disease: * Thrombocytopenia ( 160 or RR diastolic > 90) * Hypotension (defined as RR systolic 120 *mol/l) * Liver enzyme abnormalities (above 2x the upper limit of normal) * Medical history of any disease associated with immune deficiency * Signs of infection (CRP > 20 mg/L, WBC > 12x109/L or

Design outcomes

Primary

Measure	Time frame
Single-nucleotide polymorphisms (SNPs), genome-wide differential mRNA expression of monocytes obtained before and 4 hours after the first endotoxin challenge, and plasma cytokine concentration profiles upon the first and second endotoxin challenge (including but not limited to TNF*, IL-6, IL-8, and IL-10) to determine extent of endotoxin tolerance (which is expressed as the decrease in plasma cytokine levels between the first and second endotoxin challenge). These data will be integrated to determine the SNPs/transcripts that are predictive of the extent of endotoxin tolerance developed by the subjects.	—

Measure

Time frame

Single-nucleotide polymorphisms (SNPs), genome-wide differential mRNA expression of monocytes obtained before and 4 hours after the first endotoxin challenge, and plasma cytokine concentration profiles upon the first and second endotoxin challenge (including but not limited to TNF*, IL-6, IL-8, and IL-10) to determine extent of endotoxin tolerance (which is expressed as the decrease in plasma cytokine levels between the first and second endotoxin challenge). These data will be integrated to determine the SNPs/transcripts that are predictive of the extent of endotoxin tolerance developed by the subjects.

—

Secondary

Measure	Time frame
.	—

Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)