A Study of Exosome Proteomics and Hemodynamics in Sepsis

NCT ID: NCT03267160

Last Updated: 2021-02-10

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-01-18
• Study Completion Date: 2020-01-30

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.

Conditions

Hemodynamic Instability; Autophagy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Sepsis with cardiopulmonary failure

Patient with sepsis and also respiratory and heart involvement, confirmed by Hemodynamic parameters

Hemodynamic parameters

Intervention Type: DIAGNOSTIC_TEST

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

Hemodynamic parameters

Intervention Type: DIAGNOSTIC_TEST

Pulse contour cardiac output monitored heart contractility, end-diastolic volume parameters, and lung water parameters.

Interventions

Hemodynamic parameters

Pulse contour cardiac output monitored heart contractility, end-diastolic volume parameters, and lung water parameters.

Intervention Type: DIAGNOSTIC_TEST

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wen-Lin Su, PhD

Role: STUDY_DIRECTOR

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital

Locations

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

Taipei, , Taiwan

Countries

Taiwan

References

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.

Reference Type: BACKGROUND

PMID: 22968077 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23359590 (View on PubMed)

Other Identifiers

05-XD15-039

Identifier Type: -

Identifier Source: org_study_id