The effects of human endotoxemia on the functional capacity of hematopoietic stem and progenitor cells
- Conditions
- bacterial bloodstream infectionSepsis1002766510004018
- Registration Number
- NL-OMON45383
- Lead Sponsor
- Radboud Universitair Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 12
- Written informed consent
- Age >=18 and <=35 yrs
- Male
- Healthy (as confirmed by medical history, examination, ECG, blood sampling)
• 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)
• 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Characterization of human hematopoietic stem and progenitor cells before and<br /><br>after endotoxemia determined by:<br /><br><br /><br>1) Hematopoietic lineage differentiation (composition and cellularity) of the<br /><br>bone marrow compartment by FACS<br /><br>2) Functional capacity by means of ex vivo cytokine release (including but not<br /><br>limited to IL-1β, TNF-a, IL-6, IL-10, IFN-γ) upon stimulation with PAMPs (e.g.<br /><br>LPS) and pathogens (e.g. S. aureus, C. albicans, M. tuberculosis, S. pneumonia)</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Ex vivo cytokine release of alveolar macrophages upon stimulation<br /><br>• Transcriptome of hematopoietic stem and progenitor cells, blood leukocytes,<br /><br>and alveolar macrophages<br /><br>• Epigenome of hematopoietic stem and progenitor cells, blood leukocytes, and<br /><br>alveolar macrophages<br /><br>• Cellular metabolism of hematopoietic stem and progenitor cells, blood<br /><br>leukocytes, and alveolar macrophages<br /><br>• Gene polymorphisms relating to innate immune function (e.g. autophagy ATG2b<br /><br>and ATG5 SNPs)<br /><br>• Life span and transit times of different subsets of leukocytes and their<br /><br>progenitors in human bone marrow (mitotic and post-mitotic pool) and the blood<br /><br>compartment<br /><br>• Circulating cytokine concentrations upon endotoxemia<br /><br>• Vital parameters during endotoxemia (mean arterial pressure, heart rate and<br /><br>temperature)<br /><br>• Illness score during endotoxemia</p><br>