Severe SepsisCASPASEsNCT02539147
Characterization of Non-canonical Way in Inflammasome Monocytes of Patients With Severe Sepsis
An observational study of Severe Sepsis, run by Fondation Hôpital Saint-Joseph at 1 site in France.
Trial summary
Activation of caspase-4 and human caspase-5 (orthologs of caspase-11 in mice) in innate immune cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Severe Sepsis
- What is being tested?
- blood samples
- How many people
- 6 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2014to Dec 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with sepsis severe (bacterial infection associated with deterioration of at least one vital function) defined according to the criteria consensus conference
Who may be able to join
- patients with sepsis severe (bacterial infection associated with deterioration of at least one vital function) defined according to the criteria consensus conference
- patients whose diagnosis is made within 24 hours of the opening hours of Pasteur Research Laboratory
- patients with arterial catheter (not to impose an additional puncture to the patient) will be recruited in the intensive care unit of the Hospital St. Joseph. Arterial blood (20 ml) will be charged within 24 hours of the onset of severe sepsis criteria, during working hours of the laboratory of the Pasteur Institute, using vacuum tubes under heparin (Vacutainer), sent by a courier within 2 hours following the removal (to ensure that the cells are sufficiently "fresh" during processing in the laboratory)
Who cannot join
- none
Trial locations and contacts
1 site in 1 country.
France1 site
Groupe Hospitalier Paris Saint Joseph
Paris, Île-de-France Region, 75014
About this study
Activation of caspase-4 and human caspase-5 (orthologs of caspase-11 in mice) in innate immune cells.
Read the detailed description
Lipopolysaccharide (LPS) of the wall of Gram-negative bacteria is one of pathogen associated molecular patterns (PAMPs), which are recognized by cells of the innate immune system via Toll-like receptor 4 (TLR4) . The LPS / TLR4 interaction induces the secretion of a variety of proinflammatory cytokines. Among them, interleukin-1β (IL-1β) is a major cytokine, and alterations to its secretion has been associated with various diseases, such as periodic syndrome associated cryopyrin (CAPS), gout, rheumatoid arthritis or multiple sclerosis.
The release of IL-1β is controlled by a molecular platform protein, known as the inflammasome name. The canonical protein (that is to say conserved in evolution) of the inflammasome NLRP3 are NLRC4 and that engages the ASC adapter protein to activate caspase-1, which promotes the cleavage of interleukin IL-1β. Gram-negative bacteria such as Escherichia coli cause non-canonical activation of caspase-1, caspase-11In involving more NLRP3 and AUC. In mouse, caspase-11 is essential to the immune response to gram-negative bacteria, but bacterial PAMPs that are responsible for triggering of the non-canonical inflammasome remain to be identified. It has recently been shown that caspase-11 is involved in the death of the mice subjected to septic shock. The mouse model requires caspase-11-dependent mechanism, caspase-independent -1 since the CASP1 - / - mouses are also susceptible to LPS as wild type mice. A key question to be answered is whether LPS triggers similar events in human cells. If this is the case, this knowledge may be useful in drug development for treatment of sepsis.
- Conditions
- Severe Sepsis
- Being tested
- blood samples
- Keywords
- lipopolysaccharide, sepsis, caspase-4 and -5, monocytes, IL-1β and IL-1α
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplesBiological
Isolation and stimulation of monocytes, preparation of cell lysates, measurement of cytokine production, Western blot
| Study group | Role | What they receive |
|---|---|---|
| patients with severe sepsis | blood samples from patients with severe sepsis Receives: Biological: blood samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Characterize the expression of caspase-4 and -5 in by measuring the production of cytokines: IL-1β concentrations and IL-1α will determined by ELISA in the cell supernatant will be collected from monocytes stimulated or not
Measured: Two hours after blood collection : isolation and stimulation of monocytes than preparation of cell lysates
Secondary outcomes (1)
Correlate the activation of caspases-4 and -5 with IL-1β production with (canonical inflammasome) and IL-1α (Non-canonical inflammasome) measured by Western blot
Measured: Two hours after blood collection : isolation and stimulation of monocytes than preparation of cell lysates
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2015 (estimated)
- Study startSep 2014
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Severe SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondation Hôpital Saint-Joseph
- Sponsor type
- University, hospital or other
- Collaborators
- Institut Pasteur, Agency for Science, Technology and Research
- Responsible party
- Sponsor
- Investigators
- Benoit Misset, Professor, Principal investigator, Fondation Hôpital Saint-JosephJean Marc Cavaillon, Professor, Principal investigator, Unité Cytokines et Inflammation, Institut Pasteur, ParisAlessandra Mortellaro, Principal investigator, Singapore Immunology Network, Agency for Science, Technology and Research, 8A Biomedical Grove, #04-06 Immunos, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02539147
- Sponsor's protocol ID
- 2013-A01617-38
- Acronym
- CASPASEs
- Status last verified
- Aug 2015
- First submitted
- 21 Aug 2015
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Conforti-Andreoni C, Ricciardi-Castagnoli P, Mortellaro A. The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond. Cell Mol Immunol. 2011 Mar;8(2):135-45. doi: 10.1038/cmi.2010.81. Epub 2011 Jan 24.
PubMed 21258359Zambetti LP, Laudisi F, Licandro G, Ricciardi-Castagnoli P, Mortellaro A. The rhapsody of NLRPs: master players of inflammation...and a lot more. Immunol Res. 2012 Sep;53(1-3):78-90. doi: 10.1007/s12026-012-8272-z.
PubMed 22427013Vigano E, Mortellaro A. Caspase-11: the driving factor for noncanonical inflammasomes. Eur J Immunol. 2013 Sep;43(9):2240-5. doi: 10.1002/eji.201343800.
PubMed 24037676Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, Newton K, Qu Y, Liu J, Heldens S, Zhang J, Lee WP, Roose-Girma M, Dixit VM. Non-canonical inflammasome activation targets caspase-11. Nature. 2011 Oct 16;479(7371):117-21. doi: 10.1038/nature10558.
PubMed 22002608Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. doi: 10.1378/chest.101.6.1644.
PubMed 1303622
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Non-canonical Way in Inflammasome Monocytes of Patients With Severe Sepsis
- ClinicalTrials.gov ID
- NCT02539147
- Acronym / sponsor ID
- CASPASEs / 2013-A01617-38
- Conditions
- Severe Sepsis
- Keywords
- lipopolysaccharide, sepsis, caspase-4 and -5, monocytes, IL-1β and IL-1α
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Fondation Hôpital Saint-JosephUniversity, hospital or other
- Collaborators
- Institut Pasteur, Agency for Science, Technology and Research
- Study start
- Sep 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 2 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Activation of caspase-4 and human caspase-5 (orthologs of caspase-11 in mice) in innate immune cells.
Detailed description
Lipopolysaccharide (LPS) of the wall of Gram-negative bacteria is one of pathogen associated molecular patterns (PAMPs), which are recognized by cells of the innate immune system via Toll-like receptor 4 (TLR4) . The LPS / TLR4 interaction induces the secretion of a variety of proinflammatory cytokines. Among them, interleukin-1β (IL-1β) is a major cytokine, and alterations to its secretion has been associated with various diseases, such as periodic syndrome associated cryopyrin (CAPS), gout, rheumatoid arthritis or multiple sclerosis.
The release of IL-1β is controlled by a molecular platform protein, known as the inflammasome name. The canonical protein (that is to say conserved in evolution) of the inflammasome NLRP3 are NLRC4 and that engages the ASC adapter protein to activate caspase-1, which promotes the cleavage of interleukin IL-1β. Gram-negative bacteria such as Escherichia coli cause non-canonical activation of caspase-1, caspase-11In involving more NLRP3 and AUC. In mouse, caspase-11 is essential to the immune response to gram-negative bacteria, but bacterial PAMPs that are responsible for triggering of the non-canonical inflammasome remain to be identified. It has recently been shown that caspase-11 is involved in the death of the mice subjected to septic shock. The mouse model requires caspase-11-dependent mechanism, caspase-independent -1 since the CASP1 - / - mouses are also susceptible to LPS as wild type mice. A key question to be answered is whether LPS triggers similar events in human cells. If this is the case, this knowledge may be useful in drug development for treatment of sepsis.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients with severe sepsis | – | Biological: blood samplesblood samples from patients with severe sepsis |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with sepsis severe (bacterial infection associated with deterioration of at least one vital function) defined according to the criteria consensus conference
Key inclusion criteria (3 listed)
- patients with sepsis severe (bacterial infection associated with deterioration of at least one vital function) defined according to the criteria consensus conference
- patients whose diagnosis is made within 24 hours of the opening hours of Pasteur Research Laboratory
- patients with arterial catheter (not to impose an additional puncture to the patient) will be recruited in the intensive care unit of the Hospital St. Joseph. Arterial blood (20 ml) will be charged within 24 hours of the onset of severe sepsis criteria, during working hours of the laboratory of the Pasteur Institute, using vacuum tubes under heparin (Vacutainer), sent by a courier within 2 hours following the removal (to ensure that the cells are sufficiently "fresh" during processing in the laboratory)
Key exclusion criteria (1 listed)
- none
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samplesIsolation and stimulation of monocytes, preparation of cell lysates, measurement of cytokine production, Western blot | Biological | patients with severe sepsis |
Primary outcome
Characterize the expression of caspase-4 and -5 in by measuring the production of cytokines: IL-1β concentrations and IL-1α will determined by ELISA in the cell supernatant will be collected from monocytes stimulated or not
Time frame: Two hours after blood collection : isolation and stimulation of monocytes than preparation of cell lysates
1 secondary outcome
Correlate the activation of caspases-4 and -5 with IL-1β production with (canonical inflammasome) and IL-1α (Non-canonical inflammasome) measured by Western blot
Time frame: Two hours after blood collection : isolation and stimulation of monocytes than preparation of cell lysates
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2017.
- Background: PubMed 21258359Conforti-Andreoni C, Ricciardi-Castagnoli P, Mortellaro A. The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond. Cell Mol Immunol. 2011 Mar;8(2):135-45. doi: 10.1038/cmi.2010.81. Epub 2011 Jan 24.
- Background: PubMed 22427013Zambetti LP, Laudisi F, Licandro G, Ricciardi-Castagnoli P, Mortellaro A. The rhapsody of NLRPs: master players of inflammation...and a lot more. Immunol Res. 2012 Sep;53(1-3):78-90. doi: 10.1007/s12026-012-8272-z.
- Background: PubMed 24037676Vigano E, Mortellaro A. Caspase-11: the driving factor for noncanonical inflammasomes. Eur J Immunol. 2013 Sep;43(9):2240-5. doi: 10.1002/eji.201343800.
- Background: PubMed 22002608Kayagaki N, Warming S, Lamkanfi M, Vande Walle L, Louie S, Dong J, Newton K, Qu Y, Liu J, Heldens S, Zhang J, Lee WP, Roose-Girma M, Dixit VM. Non-canonical inflammasome activation targets caspase-11. Nature. 2011 Oct 16;479(7371):117-21. doi: 10.1038/nature10558.
- Background: PubMed 1303622Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992 Jun;101(6):1644-55. doi: 10.1378/chest.101.6.1644.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benoit Misset, Professor principal investigator
Fondation Hôpital Saint-Joseph
Jean Marc Cavaillon, Professor principal investigator
Unité Cytokines et Inflammation, Institut Pasteur, Paris
Alessandra Mortellaro principal investigator
Singapore Immunology Network, Agency for Science, Technology and Research, 8A Biomedical Grove, #04-06 Immunos, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Sepsis, run by Fondation Hôpital Saint-Joseph at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Characterize the expression of caspase-4 and -5 in by measuring the production of cytokines: IL-1β concentrations and IL-1α will determined by ELISA in the cell supernatant will be collected from monocytes stimulated or not (time frame: Two hours after blood collection : isolation and stimulation of monocytes than preparation of cell lysates). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02539147, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2017.