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Sepsis-damaged Organs-double-markers Identification of Organ Failure Using Fluorescent Nanoparticle Tracking Analysis

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ClinicalTrials.gov Identifier: NCT03222986
Recruitment Status : Recruiting
First Posted : July 19, 2017
Last Update Posted : July 13, 2018
Sponsor:
Information provided by (Responsible Party):
Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Brief 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. NTA double markers identification will be a smart method to understand the exosome subpopulations.

Condition or disease
Sepsis With Multiple Organ Dysfunction (MOD)

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.


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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Institutional Review Board
Actual Study Start Date : July 1, 2017
Estimated Primary Completion Date : December 19, 2018
Estimated Study Completion Date : January 20, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Group/Cohort
Sepsis with organ failure
Patients have organ failure
Sepsis without organ failure
Patients have no organ failure



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. The inflammatory process also will be validated by cytokines analysis. [ Time Frame: within 24 hrs. ]
    The inflammatory process also will be validated by cytokines analysis.

  2. NTA double markers identification will be a smart method to understand the exosome subpopulations. [ Time Frame: within 24 hrs. ]
    NTA double markers identification will be a smart method to understand the exosome


Biospecimen Retention:   Samples Without DNA
blood, urine


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
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"
Criteria

Inclusion Criteria:

Septic patients will have an "acute change in total SOFA score ≥ 2 points consequent to infection" Sepsis with organ failure Sepsis without organ failure

Exclusion Criteria:

patients who had chronic respiratory failure with ventilator dependence chronic renal failure with regular hemodialysis


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03222986


Contacts
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Contact: Wen-Lin Su, PhD +886-2-66289779 williamsu2007@gmail.com

Locations
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Taiwan
Wen-Lin Su Recruiting
Taipei, Taiwan
Contact: Wen-Lin Su, PhD         
Sponsors and Collaborators
Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
Investigators
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Study Director: Wen-Lin Su, PhD Division of Pulmonary and Critical Care Medicine Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

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.

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Responsible Party: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
ClinicalTrials.gov Identifier: NCT03222986     History of Changes
Other Study ID Numbers: 04-XD37-104
First Posted: July 19, 2017    Key Record Dates
Last Update Posted: July 13, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation:
sepsis, nanoparticle tracking analysis

Additional relevant MeSH terms:
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Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes