To determine the effects of the CytoSorb hemoperfusion column on the development of immunoparalysis in a repeated human endotoxemia model, which is reflected by attenuated plasma cytokine levels during the second LPS challenge.
ID
Source
Brief title
Condition
- Immune disorders NEC
- Bacterial infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Plasma IL-6 levels during the second LPS challenge. Comparison of CytoSorb
group with control group. IL-6 is an archetypal pro-inflammatory cytokine with
high relevance to sepsis.
Secondary outcome
- Plasma levels of other inflammatory cytokines (including, but not limited to
IL-6, IL-8, IL-10, MCP-1, CXCL-10, MIP-1*, MIP-1*, and G-CSF) during the second
LPS chal-lenge.
- mHLA-DR expression.
- Plasma levels of inflammatory cytokines (including, but not limited to IL-6,
IL-8, IL-10, MCP-1, CXCL-10, MIP-1*, MIP-1*, and G-CSF) during the first LPS
challenge
- Norepinephrine sensitivity during the first LPS challenge.
- Cytokine concentrations in afferent and efferent tubing of the CytoSorb
filter. Togeth-er with the blood flow, cytokine clearance by the filter can be
calculated.
- Endotoxemia-induced changes in leukocyte numbers and differential count
- Endotoxemia-induced increase in body temperature
- Endotoxemia-induced symptoms
- Endotoxemia-induced hemodynamic alterations
- Endotoxemia-induced increase in markers of endothelial injury (VCAM/ICAM)
Background summary
Sepsis is a major health care burden with high mortality rates and increasing
incidence. Over the last couple of decades, it has become increasingly clear
that not hyperinflammation, but a protracted immunosuppressive state known as
immunoparalysis is the overriding immune disorder in sepsis. Patients suffering
from immunoparalysis are highly susceptible towards infectious diseases, and
secondary infections attribute to the high mortality in these patients to a
great extent. Immunoparalysis is mainly caused by high concentrations of
inflammatory cytokines in the early stages of sepsis. These cytokines are
produced primarily in the tissues. Treatment options aimed at capturing these
cytokines might aid in the prevention of immunoparalysis and might thereby
improve outcome for sepsis patients. The cytokine-adsorbing hemofilter CytoSorb
might represent such an option. In the present study, we aim to investigate
whether CytoSorb hemoperfusion prevents immunoparalysis effectively in a group
of healthy volunteers who will undergo an endotoxin challenge twice.
Study objective
To determine the effects of the CytoSorb hemoperfusion column on the
development of immunoparalysis in a repeated human endotoxemia model, which is
reflected by attenuated plasma cytokine levels during the second LPS challenge.
Study design
Open-label randomized controlled trial. Twenty-four healthy subjects will be
divided into two groups (12 vs 12): the CytoSorb group and a control group.
Both groups will undergo an endotoxin challenge twice. The CytoSorb group will
be treated with CytoSorb hemoperfusion for six hours during the first endotoxin
challenge, whereas the control group will receive no intervention. Blood
samples will be obtained at predefined timepoints throughout the experiment to
construct time-concentration curves of various inflammatory cytokines. One week
later, the experiment will be repeated, this time without hemoperfusion
treatment. After 12 subjects (6 vs 6) have completed the study, an interim
analysis on safety data will be performed.
Intervention
CytoSorb hemoperfusion for six hours
Study burden and risks
Participants will visit the hospital four times: for the screening visit, twice
for the endotoxin challenges and once for follow-up. Total time-investment will
be approximately 21 hours in 8 days. We have extensive experience with
performing endotoxin experiments, which are classified as being of negligible
risk. CytoSorb hemoperfusion has been applied in > 60.000 patients without any
safety concerns. Taking all of this into account, we feel that the remaining
risks do not outweigh the medical and scientific relevance of the study and
that the study is proportional.
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
- Written informed consent
- Male
- Age * 18 and * 35 years
- Healthy (as determined by medical history, physical examination, vital signs,
12-lead electrocardiogram (ECG) and routine clinical laboratory parameters)
Exclusion criteria
- Use of any medication
- Smoking
- Hypersensitivity to any of the (non)investigational products or their
excipients
- History of:
- Any immune-related disorder
- Aneurysmal or hemorrhagic disease
- Renal or hepatic impairment
- Recent infection (<2 weeks)
- Previous LPS administration
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL71293.091.19 |