Sepsis With Multiple Organ Dysfunction (MOD)NCT03222986
Sepsis-damaged Organs-double-markers Identification of Organ Failure Using Fluorescent Nanoparticle Tracking Analysis
An observational study of Sepsis With Multiple Organ Dysfunction (MOD), run by Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation at 1 site in Taiwan.
Trial summary
Systematic establishment of exosome proteomics in co-culture medium and clinical sepsis specimens will be done. Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis. The inflammatory process also will be validated by cytokines analysis. Read more about this study
- Who is it for?
- Ages 20 to 99 years
- Conditions the study is for
- Sepsis With Multiple Organ Dysfunction (MOD)
- How many people
- 60 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Jul 2017to 19 Dec 2019
- 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 20 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All included patients will be classified according to the sepsis-3 criteria, also treat according to surviving sepsis campaign guidelines. Every enrolled patients will be traced the infection sources with positive culture results. Enrolled septic patients will have an "acute change in total SOFA score ≥ 2 points consequent to infection"
Who may be able to join
- Septic patients will have an "acute change in total SOFA score ≥ 2 points consequent to infection" Sepsis with organ failure Sepsis without organ failure
Who cannot join
- patients who had chronic respiratory failure with ventilator dependence chronic renal failure with regular hemodialysis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Institutional Review Board
Systematic establishment of exosome proteomics in co-culture medium and clinical sepsis specimens will be done. Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis. The inflammatory process also will be validated by cytokines analysis. NTA double markers identification will be a smart method to understand the exosome subpopulations.
Read the detailed description
Background: Sepsis, defined as life-threatening organ dysfunction due to a dysregulated host response to infection, continues to be a source of considerable morbidity and mortality. 19 million cases are seen worldwide each year. Many animal sepsis models had found that sepsis induced multiple organ failure. Ubiquitination, autophagy, apoptosis may involve the process of sepsis related multiple organ failure. Mass spectrometry-based proteomics studies in clinical populations and in rodent and mammalian animal models had started with discovered many novel biomarkers of sepsis. Esoxomes had been found in blood or urine presented the signal of autophagy and apoptosis. Recently, nanoparticle tracking analysis (NTA) was used as a new method for direct and real-time analysis of exosomes. These make it possible to study the exosome biomarkers to analyze septic patients with multiple organ failure.
Aims of the study: This research will be the first study not only to set up macrophage co-cultured with human organ cell models for exosomes secretions but also collect purified exosomes in blood and urine from septic patients. Proteomics studies in exosomes from cell culture and clinical specimens. Analyze ubiquitination, autophage, and apoptosis related biomarkers of exosomes by bioinformatics. Use NTA to set up newly diagnostic methods, to judge the specific organ damage of septic patient by exosomes autophagy-apoptosis biomarkers.
Materials and Methods: In 1st year, LPS (lipopolysaccharide) stimulated macrophage co-cultured with human organ cells will be set up. Exosomes will be isolated and purified from different groups. ScFv (single chain fragments of antibody) will be selected for blocking infection related exosome's transmission. The 2nd year, a total of 60 patients with infection and positive culture results will be included, of whom 30 septic patients had at least one organ failure, others will have only infection. All patients included and classified according to the sepsis-3 criteria. Clinical specimens will be collected from August 2017 to July 2019. Exosome will be isolated and purified. Magnetic beads purification, 2D gel electrophoresis, MALDI-TOF, and bioinformatics will be used to analyze proteomics of exosomes and association of organ-specific markers, autophagy, and apoptosis markers. Western blotting will be done to prove the proteins found by proteomics. Cytokines array in blood also confirm and correlate to autophagy. Finally, we will use nanoparticle tracking analysis with double markers identification to understand the exosome subpopulations of specific organ and autophagy-apoptosis biomarkers.
Possible effect: Systematic establishment of exosome proteomics in co-culture medium and clinical sepsis specimens will be done. In vitro study, ScFv exploring will help to block exsomes uptake as a possible therapeutic method. Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis. The inflammatory process also will be validated by cytokines analysis. NTA double markers identification will be a smart method to understand the exosome subpopulations.
- Keywords
- sepsis, nanoparticle tracking analysis
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Sepsis with organ failure | Patients have organ failure | |
| Sepsis without organ failure | Patients have no organ failure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis
Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis
Measured: within 24 hrs.
Secondary outcomes (2)
The inflammatory process also will be validated by cytokines analysis.
The inflammatory process also will be validated by cytokines analysis.
Measured: within 24 hrs.
NTA double markers identification will be a smart method to understand the exosome subpopulations.
NTA double markers identification will be a smart method to understand the exosome
Measured: within 24 hrs.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2017
- Study start1 Jul 2017
- Primary completion19 Dec 2019
- Study completion19 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sepsis With Multiple Organ Dysfunction (MOD)Studies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wen-Lin Su, PhD, Study director, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03222986
- Sponsor's protocol ID
- 04-XD37-104
- Status last verified
- Feb 2020
- First submitted
- 17 Jul 2017
- Last updated
- 4 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
1. Dombrovskiy, V.Y., et al., Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med, 2007. 35(5): p. 1244-50. 2. Angus, D.C., et al., Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med, 2001. 29(7): p. 1303-10. 3. Martin, G.S., et al., The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med, 2003. 348(16): p. 1546-54. 4. van Zanten, A.R., The golden hour of antibiotic administration in severe sepsis: avoid a false start striving for gold*. Crit Care Med, 2014. 42(8): p. 1931-2. 5. Duran-Bedolla, J., et al., Sepsis, mitochondrial failure and multiple organ dysfunction. Clin Invest Med, 2014. 37(2): p. E58-69.
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Institutional Review Board
- ClinicalTrials.gov ID
- NCT03222986
- Acronym / sponsor ID
- 04-XD37-104
- Keywords
- sepsis, nanoparticle tracking analysis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationUniversity, hospital or other
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 19 Dec 2019 (actual)
- Study completion
- 19 Dec 2019 (actual)
- First posted
- 19 Jul 2017 (actual)
- 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.
Systematic establishment of exosome proteomics in co-culture medium and clinical sepsis specimens will be done. Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis. The inflammatory process also will be validated by cytokines analysis. NTA double markers identification will be a smart method to understand the exosome subpopulations.
Detailed description
Background: Sepsis, defined as life-threatening organ dysfunction due to a dysregulated host response to infection, continues to be a source of considerable morbidity and mortality. 19 million cases are seen worldwide each year. Many animal sepsis models had found that sepsis induced multiple organ failure. Ubiquitination, autophagy, apoptosis may involve the process of sepsis related multiple organ failure. Mass spectrometry-based proteomics studies in clinical populations and in rodent and mammalian animal models had started with discovered many novel biomarkers of sepsis. Esoxomes had been found in blood or urine presented the signal of autophagy and apoptosis. Recently, nanoparticle tracking analysis (NTA) was used as a new method for direct and real-time analysis of exosomes. These make it possible to study the exosome biomarkers to analyze septic patients with multiple organ failure.
Aims of the study: This research will be the first study not only to set up macrophage co-cultured with human organ cell models for exosomes secretions but also collect purified exosomes in blood and urine from septic patients. Proteomics studies in exosomes from cell culture and clinical specimens. Analyze ubiquitination, autophage, and apoptosis related biomarkers of exosomes by bioinformatics. Use NTA to set up newly diagnostic methods, to judge the specific organ damage of septic patient by exosomes autophagy-apoptosis biomarkers.
Materials and Methods: In 1st year, LPS (lipopolysaccharide) stimulated macrophage co-cultured with human organ cells will be set up. Exosomes will be isolated and purified from different groups. ScFv (single chain fragments of antibody) will be selected for blocking infection related exosome's transmission. The 2nd year, a total of 60 patients with infection and positive culture results will be included, of whom 30 septic patients had at least one organ failure, others will have only infection. All patients included and classified according to the sepsis-3 criteria. Clinical specimens will be collected from August 2017 to July 2019. Exosome will be isolated and purified. Magnetic beads purification, 2D gel electrophoresis, MALDI-TOF, and bioinformatics will be used to analyze proteomics of exosomes and association of organ-specific markers, autophagy, and apoptosis markers. Western blotting will be done to prove the proteins found by proteomics. Cytokines array in blood also confirm and correlate to autophagy. Finally, we will use nanoparticle tracking analysis with double markers identification to understand the exosome subpopulations of specific organ and autophagy-apoptosis biomarkers.
Possible effect: Systematic establishment of exosome proteomics in co-culture medium and clinical sepsis specimens will be done. In vitro study, ScFv exploring will help to block exsomes uptake as a possible therapeutic method. Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis. The inflammatory process also will be validated by cytokines analysis. NTA double markers identification will be a smart method to understand the exosome subpopulations.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sepsis with organ failure | – | –Patients have organ failure |
| Sepsis without organ failure | – | –Patients have no organ failure |
Who may qualify
- Ages
- 20 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All included patients will be classified according to the sepsis-3 criteria, also treat according to surviving sepsis campaign guidelines. Every enrolled patients will be traced the infection sources with positive culture results. Enrolled septic patients will have an "acute change in total SOFA score ≥ 2 points consequent to infection"
Key inclusion criteria (1 listed)
- Septic patients will have an "acute change in total SOFA score ≥ 2 points consequent to infection" Sepsis with organ failure Sepsis without organ failure
Key exclusion criteria (1 listed)
- patients who had chronic respiratory failure with ventilator dependence chronic renal failure with regular hemodialysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis
Time frame: within 24 hrs.
Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis
2 secondary outcomes
The inflammatory process also will be validated by cytokines analysis.
Time frame: within 24 hrs.
NTA double markers identification will be a smart method to understand the exosome subpopulations.
Time frame: within 24 hrs.
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 4 Feb 2021.
- Background1. Dombrovskiy, V.Y., et al., Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med, 2007. 35(5): p. 1244-50. 2. Angus, D.C., et al., Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med, 2001. 29(7): p. 1303-10. 3. Martin, G.S., et al., The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med, 2003. 348(16): p. 1546-54. 4. van Zanten, A.R., The golden hour of antibiotic administration in severe sepsis: avoid a false start striving for gold*. Crit Care Med, 2014. 42(8): p. 1931-2. 5. Duran-Bedolla, J., et al., Sepsis, mitochondrial failure and multiple organ dysfunction. Clin Invest Med, 2014. 37(2): p. E58-69.
- Individual participant dataSharing planned: No
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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.
Wen-Lin Su, PhD study director
Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
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 Sepsis With Multiple Organ Dysfunction (MOD), run by Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation at 1 site in Taiwan.
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 1 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 4 Feb 2021. 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 Taiwan. 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?
Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis (time frame: within 24 hrs.). 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 NCT03222986, which also lists 1 linked publication.
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 4 Feb 2021.