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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

Tracking Information
First Submitted Date July 17, 2017
First Posted Date July 19, 2017
Last Update Posted Date July 13, 2018
Actual Study Start Date July 1, 2017
Estimated Primary Completion Date December 19, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 20, 2017)
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
Original Primary Outcome Measures
 (submitted: July 17, 2017)
Ubiquitination-autophagy-apoptosis biomarkers in exosomes will be detected and correlated to specific organ failure in sepsis [ Time Frame: within 24 hrs. ]
Change History Complete list of historical versions of study NCT03222986 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures
 (submitted: July 20, 2017)
  • 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.
  • 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
Original Secondary Outcome Measures
 (submitted: July 17, 2017)
  • 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. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Sepsis-damaged Organs-double-markers Identification of Organ Failure Using Fluorescent Nanoparticle Tracking Analysis
Official Title Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation Institutional Review Board
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.
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 Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
blood, urine
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"
Condition Sepsis With Multiple Organ Dysfunction (MOD)
Intervention Not Provided
Study Groups/Cohorts
  • Sepsis with organ failure
    Patients have organ failure
  • Sepsis without organ failure
    Patients have no organ failure
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 17, 2017)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 20, 2019
Estimated Primary Completion Date December 19, 2018   (Final data collection date for primary outcome measure)
Eligibility 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

Sex/Gender
Sexes Eligible for Study: All
Ages 20 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Wen-Lin Su, PhD +886-2-66289779 williamsu2007@gmail.com
Listed Location Countries Taiwan
Removed Location Countries  
 
Administrative Information
NCT Number NCT03222986
Other Study ID Numbers 04-XD37-104
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
Study Sponsor Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
Collaborators Not Provided
Investigators
Study Director: Wen-Lin Su, PhD Division of Pulmonary and Critical Care Medicine Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
PRS Account Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
Verification Date July 2018