Clinical trial NCT03267160: A Study of Exosome Proteomics and Hemodynamics in Sepsis
Official title: An Observation Study of Exosome Proteomics Released From Cardiopulmonary Organs and Hemodynamic Parameters in Sepsis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemodynamic Instability
Autophagy
Lead sponsor: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
Sponsor class: OTHER
First posted: 2017-08-30
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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.

Eligibility 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.

Primary outcomes:
measure: Change of hemodynamic parameters (heart contractility: CFI)
timeFrame: Baseline, 6 hours
measure: Change of hemodynamic parameters (preload: GEDI)
timeFrame: Baseline, 6 hours
measure: Change of hemodynamic parameters (afterload: SVRI)
timeFrame: Baseline, 6 hours
measure: Change of hemodynamic parameters (fluid responsiveness: SVV)
timeFrame: Baseline, 6 hours, one day, and 3 days
measure: Change of hemodynamic parameters (lung water: ELWI)
timeFrame: Baseline, 6 hours
measure: Change of hemodynamic parameters (lung permeability: PVPI)
timeFrame: Baseline, 6 hours
Secondary outcomes:
measure: Autophagy biomarkers in exosomes: LC3II (Western blots)
timeFrame: 6 hours
measure: Autophagy biomarkers in exosomes: LC3II (NTA)
timeFrame: 6 hours
measure: Autophagy modifiers in exosomes: mTOR (Western blots)
timeFrame: 6 hours
measure: Autophagy modifiers in exosomes: mTOR (NTA)
timeFrame: 6 hours
measure: Autophagy modifiers in exosomes: HSP70 (Western blots)
timeFrame: 6 hours
measure: Autophagy modifiers in exosomes: HSP70 (NTA)
timeFrame: 6 hours
measure: Autophagy modifiers in exosomes: sequestosome 1 (Western blots)
timeFrame: 6 hours
measure: Autophagy modifiers in exosomes: sequestosome 1 (NTA)
timeFrame: 6 hours
measure: Exosomes marker: CD9 (Western blots)
timeFrame: 6 hours
measure: Exosomes marker: CD9 (NTA)
timeFrame: 6 hours
measure: ICU mortality
timeFrame: Up to 30 days
measure: 28-day mortality
timeFrame: Up to 28 days
measure: Hospital mortality
timeFrame: Up to 90 days
measure: Length of stay in ICU
timeFrame: Up to 30 days
measure: Length of stay in hospital
timeFrame: Up top 90 days
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
Study officials:
affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital
name: Wen-Lin Su, PhD
role: STUDY_DIRECTOR
References:
citation: Lo S, Yuan SS, Hsu C, Cheng YJ, Chang YF, Hsueh HW, Lee PH, Hsieh YC. Lc3 over-expression improves survival and attenuates lung injury through increasing autophagosomal clearance in septic mice. Ann Surg. 2013 Feb;257(2):352-63. doi: 10.1097/SLA.0b013e318269d0e2.
citation: Gao M, Ha T, Zhang X, Wang X, Liu L, Kalbfleisch J, Singh K, Williams D, Li C. The Toll-like receptor 9 ligand, CpG oligodeoxynucleotide, attenuates cardiac dysfunction in polymicrobial sepsis, involving activation of both phosphoinositide 3 kinase/Akt and extracellular-signal-related kinase signaling. J Infect Dis. 2013 May 1;207(9):1471-9. doi: 10.1093/infdis/jit036. Epub 2013 Jan 28.