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Trial record 24 of 127 for:    exosomes

A Study of Exosome Proteomics and Hemodynamics in Sepsis

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ClinicalTrials.gov Identifier: NCT03267160
Recruitment Status : Active, not recruiting
First Posted : August 30, 2017
Last Update Posted : January 24, 2019
Sponsor:
Information provided by (Responsible Party):
Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Brief Summary:
This research will be the first study for exosomes purified in blood and urine from septic patients who had multiple organ failures. Proteomics studies in exosomes from blood or urine specimens. Analyze autophage, and apoptosis related biomarkers of exosomes by bioinformatics. To find the correlations between exosomes biomarkers and hemodynamic parameters.

Condition or disease Intervention/treatment
Hemodynamic Instability Autophagy Diagnostic Test: Hemodynamic parameters

Detailed Description:

Background: Sepsis, defined as an infection with evidence of systemic infection, continues to be a source of considerable morbidity and mortality. Many animal sepsis models had found that sepsis induced multiple organ failure. 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. On the other hand, pulse contour cardiac output (PiCCO) can calculate hemodynamic parameters that had been used for evaluation in cardiopulmonary failure of sepsis.

Aims of the study: This research will be the first study for exosomes purified in blood and urine from septic patients who had multiple organ failures. Proteomics studies in exosomes from blood or urine specimens. Analyze autophage, and apoptosis related biomarkers of exosomes by bioinformatics. To find the correlations between exosomes biomarkers and hemodynamic parameters.

Materials and Methods: A total of 30 patients with sepsis, septic shock, or multiple organ failure will be included, of whom 15 septic patients had cardiopulmonary organ failure, others will be not. All patients included and classified according to the surviving sepsis campaign criteria, also treat according to surviving sepsis campaign guidelines. Data will be collected from January 2016 to December 2016. Exosome will be isolated and purified by sucrose gradient ultracentrifugation. Magnetic beads purification, 2D gel electrphoresis, and MALDI-TOF will be used to analyze proteomics of exosome in urine or blood of septic patients. Western blotting will be done to prove the proteins found by proteomics. Pulse contour cardiac output monitored heart contractility, end-diastolic volume parameters, and lung water parameters. Finally, to find the correlations between exosome specific organ and autophagy-apoptosis biomarkers and hemodynamic parameters.

Possible effect: Systematic establishment of exosome proteomics in blood and urine from septic patients who had multiple organ failure or not will be done. Autophagy-apoptosis biomarkers in exosomes will be detected and correlated to hemodynamic parameters, to judge specific organ failure in sepsis.


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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: An Observation Study of Exosome Proteomics Released From Cardiopulmonary Organs and Hemodynamic Parameters in Sepsis
Actual Study Start Date : January 18, 2017
Estimated Primary Completion Date : December 30, 2019
Estimated Study Completion Date : December 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Group/Cohort Intervention/treatment
Sepsis with cardiopulmonary failure
Patient with sepsis and also respiratory and heart involvement, confirmed by Hemodynamic parameters
Diagnostic Test: Hemodynamic parameters
Pulse contour cardiac output monitored heart contractility, end-diastolic volume parameters, and lung water parameters.

Sepsis without cardiopulmonary failure
Patient with sepsis without respiratory and heart involvement
Diagnostic Test: Hemodynamic parameters
Pulse contour cardiac output monitored heart contractility, end-diastolic volume parameters, and lung water parameters.




Primary Outcome Measures :
  1. Change of hemodynamic parameters (heart contractility: CFI) [ Time Frame: Baseline, 6 hours ]
    Change from Baseline Cardiac function index (CFI; L/min) at 6 hours. Cardiac function index (CFI; L/min) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany)

  2. Change of hemodynamic parameters (preload: GEDI) [ Time Frame: Baseline, 6 hours ]
    Change from Baseline Global end-diastolic index (GEDI; mL/m2) at 6 hours. Global end-diastolic index (GEDI; mL/m2) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany).

  3. Change of hemodynamic parameters (afterload: SVRI) [ Time Frame: Baseline, 6 hours ]
    Change from Baseline Systemic vascular resistance index (SVRI; dynes x sec x cm-5/m2) at 6 hours. Systemic vascular resistance index (SVRI; dynes x sec x cm-5/m2) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany).

  4. Change of hemodynamic parameters (fluid responsiveness: SVV) [ Time Frame: Baseline, 6 hours, one day, and 3 days ]
    Change from Baseline Stroke volume variation (SVV, %) at 6 hours. Stroke volume variation (SVV, %) will be calculated spontaneously by PiCCO2 device (Pulsion Medical Systems, Munich, Germany).

  5. Change of hemodynamic parameters (lung water: ELWI) [ Time Frame: Baseline, 6 hours ]
    Change from Baseline Extravascular lung water index (EVLWI; mL/kg) at 6 hours. Extravascular lung water index (EVLWI; mL/kg) will be calculated by the PiCCO device (Pulsion Medical Systems, Munich, Germany). EVLWI means total water in lung tissue, it increase in pulmonary edema or ARDS. PVPI means pulmonary vascular permeability and always high in ARDS (acute respiratory distress syndrome)

  6. Change of hemodynamic parameters (lung permeability: PVPI) [ Time Frame: Baseline, 6 hours ]
    Change from Baseline pulmonary vascular permeability index (PVPI; ratio) at 6 hours. pulmonary vascular permeability index (PVPI) will be calculated by the PiCCO device (Pulsion Medical Systems, Munich, Germany). EVLWI means total water in lung tissue, it increase in pulmonary edema or ARDS. PVPI means pulmonary vascular permeability and always high in ARDS (acute respiratory distress syndrome)


Secondary Outcome Measures :
  1. Autophagy biomarkers in exosomes: LC3II (Western blots) [ Time Frame: 6 hours ]
    LC3II appear during phagosome-lysomone fusion. Exosome will be collected from serum of sepsis. LC3II will be detected and identified by Western blots.

  2. Autophagy biomarkers in exosomes: LC3II (NTA) [ Time Frame: 6 hours ]
    LC3II appear during phagosome-lysomone fusion. Exosome will be collected from serum of sepsis. Later, LC3II will be marked and combined analysis by Nanoparticle tracing analysis. Concentrations (particles/mL) by size (nm) or Intensity (a.u.) by size (nm)

  3. Autophagy modifiers in exosomes: mTOR (Western blots) [ Time Frame: 6 hours ]
    mammalian target of rapamycin (mTOR) may modulate the process of autophagy. Exosome will be collected from serum of sepsis. mTOR will be detected and identified by Western blots.

  4. Autophagy modifiers in exosomes: mTOR (NTA) [ Time Frame: 6 hours ]
    mammalian target of rapamycin (mTOR) may modulate the process of autophagy. Exosome will be collected from serum of sepsis. mTOR will be marked and combined analysis by Nanoparticle tracing analysis. Concentrations (particles/mL) by size (nm) or Intensity (a.u.) by size (nm)

  5. Autophagy modifiers in exosomes: HSP70 (Western blots) [ Time Frame: 6 hours ]
    heat-shock protein 70 (HSP70) may modulate the process of autophagy. Exosome will be collected from serum of sepsis. HSP70 will be detected and identified by Western blots.

  6. Autophagy modifiers in exosomes: HSP70 (NTA) [ Time Frame: 6 hours ]
    heat-shock protein 70 (HSP70) may modulate the process of autophagy. Exosome will be collected from serum of sepsis. Later, HSP70 will be marked and combined analysis by Nanoparticle tracing analysis. Concentrations (particles/mL) by size (nm) or Intensity (a.u.) by size (nm)

  7. Autophagy modifiers in exosomes: sequestosome 1 (Western blots) [ Time Frame: 6 hours ]
    sequestosome 1 (SQSMT1/p62) may modulate the process of autophagy. Exosome will be collected from serum of sepsis. sequestosome 1 will be detected and identified by Western blots.

  8. Autophagy modifiers in exosomes: sequestosome 1 (NTA) [ Time Frame: 6 hours ]
    sequestosome 1 (SQSMT1/p62) may modulate the process of autophagy. Exosome will be collected from serum of sepsis. Later, sequestosome 1 will be marked and combined analysis by Nanoparticle tracing analysis. Concentrations (particles/mL) by size (nm) or Intensity (a.u.) by size (nm)

  9. Exosomes marker: CD9 (Western blots) [ Time Frame: 6 hours ]
    CD9 is the exosome surface marker. Exosome will be collected from serum of sepsis. CD9 will be detected and identified by Western blots.

  10. Exosomes marker: CD9 (NTA) [ Time Frame: 6 hours ]
    CD9 is the exosome surface marker. Exosome will be collected from serum of sepsis. Later, CD9 will be marked and combined analysis by Nanoparticle tracing analysis. Concentrations (particles/mL) by size (nm) or Intensity (a.u.) by size (nm)

  11. ICU mortality [ Time Frame: Up to 30 days ]
    ICU mortality (%), mortality during ICU admission/total ICU admission

  12. 28-day mortality [ Time Frame: Up to 28 days ]
    28-day mortality (%), mortality during 28-day/total 28-day admission

  13. Hospital mortality [ Time Frame: Up to 90 days ]
    Hospital mortality (%), mortality during hospitalizaiton/total hospital admission

  14. Length of stay in ICU [ Time Frame: Up to 30 days ]
    Length of stay in ICU (days)

  15. Length of stay in hospital [ Time Frame: Up top 90 days ]
    Length of stay in hospital (days)


Biospecimen Retention:   Samples Without DNA
Blood and urine, extract exosome collection


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:   Non-Probability Sample
Study Population

Sepsis was defined as a life-threatening organ dysfunction due to a dysregulated host response to infection.

Patient with sepsis who was admitted to ICU. PiCCO hemodynamics was setted

Criteria

Inclusion Criteria:

  1. Patients with sepsis who admit to ICU
  2. Sepsis diagnostic criteria: acute change in total SOFA score ≥ 2 points attributable to infection
  3. Pulse indicator continuous cardiac output monitor (PiCCO) is accept by patient for hemodynamic monitoring

Exclusion Criteria:

  1. Patients with acute SOFA changes < 2 points are excluded
  2. auria, no urine can be collected
  3. Previous cardiopulmonary co-morbidity. Chronic respiratory failure with ventilator dependence and chronic heart failure.

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): NCT03267160


Locations
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Taiwan
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
Taipei, Taiwan, 23142
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, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Publications:
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Responsible Party: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
ClinicalTrials.gov Identifier: NCT03267160     History of Changes
Other Study ID Numbers: 05-XD15-039
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: January 24, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes