The Effect and Mechanism of lncRNA NBR2 Regulating Endothelial Pyroptosis by Targeting GSDMD in Sepsis

NCT04427371 | Unknown

• 1 other identifier: SoutheastUChina
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a life-threatening disease characterized by multi-organ failure due to dysregulated host response to infection, with high global mortality of 30-50%. One of the most important pathophysiologic hallmarks in sepsis is vascular endothelial injury that contributes to the severity and outcome of the syndrome. Effective treatments for endothelial cell injury in sepsis have been lacking to improve prognosis. Endothelial pyroptosis is a vital mechanism of vascular endothelial injury in sepsis; mitigation or abolishment of endothelial cell pyroptosis alleviate vascular endothelial damage and improve the prognosis of sepsis mice. Gasdermin D (GSDMD) mediated endothelial pyroptosis plays a critical role in modulating vascular endothelial injury in sepsis. Long non-coding RNA (lncRNA), as a class of non-coding protein RNA longer than 200 kD, contributes to a variety of cell biological processes. The dysregulation of lncRNA results in the occurrence and development of tumors, diabetes, sepsis and other diseases. Therefore, we detected lncRNA and mRNA expression profile in 26 blood samples of septic patients using Arraystar LncRNA Microarray. We found lncRNA NBR2 regulates septic endothelial pyroptosis. To assess any correlation of pyroptosis levels with relevant endothelial cell injury parameters and determine the prognostic value in septic patients. we measured the levels of pyroptosis in patients admitted to the Department of Critical Care Medicine for sepsis and investigated the correlation with related markers of endothelium injury. Furthermore, we determined the prognostic value of pyroptosis levels for the mortality of patients with sepsis.

Conditions

Sepsis

Keywords

endothelial cell injury; pyroptosis; lncRNA NBR2; gasdermin D

Outcome Measures

Primary Outcomes (1)

• 28-day mortality

  all-cause 28-day mortality

  28-day

Study Arms (2)

survivors

Improve or under treatment

Other: the levels of pyroptosis

nonsurvivors

all-cause 28-day mortality

Other: the levels of pyroptosis

Interventions

the levels of pyroptosis OTHER

Blood samples were taken to detect plasma lncRNA NBR2 levels and GSDMD protein level.

nonsurvivors; survivors

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

sepsis was defined according to "sepsis 3.0", which including suspected or confirmed infection and increased SOFA ≥ 2, confirmed by two experienced intensive care physicians. The infection was defined on the basis of infection sites, clinical features, clinical microbiology, and imaging tests. Septic shock was defined as a vasopressor requirement to maintain a mean arterial pressure of 65 mmHg or greater and serum lactate level greater than 2 mmol/L in the absence of hypovolemia.

You may qualify if:

• Suspected or confirmed infection
• The sequential organ failure score (SOFA score) increases by more than or equal to 2 points on the basis
• Sign the informed consent

You may not qualify if:

• the age \< 18 or \> 80 years of age
• pregnant
• tumor
• viral hepatitis or liver cirrhosis
• chronic renal tubular nephritis, chronic renal insufficiency
• ulcerative colitis or crohn's disease
• active systemic lupus erythematosus (SLE)
• acute myocardial infarction
• acute pancreatitis
• engaged in other clinical subjects

Sponsors & Collaborators

• Jianfeng Xie: lead

Study Sites (1)

Zhongda Hospital, School of Medicine, Southeast University

Nanjing, Jiangsu, 210009, China

RECRUITING

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Fei Peng, Dr

CONTACT

025-83262553; afei0312@163.com

Yi Yang, Prof.

CONTACT

025-83262553; yiyiyang2004@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 11, 2020
• Study Start: May 22, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: June 11, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)