Correlation of Memory CD8+ T Cells With Sepsis Severity and Mortality: a Single-center, Unblinded, Prospective, Non-interventional, Observational Study

Sepsis Clinical Trial

Official title:

Correlation of Memory CD8+ T Cells With Sepsis Severity and Mortality: a Single-center, Unblinded, Prospective, Non-interventional, Observational Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05875740
• Other study ID #: ZJC202304
• Status: Recruiting
• Start date: February 24, 2024
• Est. completion date: May 31, 2025

Study information

• Verified date: April 2023
• Source: Wuhan Union Hospital, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Severe sepsis is the most common cause of death among critically ill patients in non-coronary intensive care units (ICU). Sustained excessive inflammation and immune dysfunction have been confirmed to play a key role in organ damage and early death of sepsis patients. Therefore, it is important to reduce excessive inflammatory response mediated by immune cells and pro-inflammatory cytokines in the acute phase of sepsis.

Single-cell RNA sequencing performed on both septic patients and mice suggest that changes in Tcm (CD3+ CD8+ CD44+ CD127+ CD62L+) and Tem (CD3+ CD8+ CD44+ CD127+ CD62L -) in the acute phase of sepsis may play an important role in sepsis. In addition, animal researches showed that Tcm and Tem decreased decreased continuously at 24, 48 and 72h after cecal ligation and perforation (CLP) in mice, and the adoptive transfer of Tcm , sorting from spleen of mice 24h after CLP , but not Tem improved 7-day survival rate of sepsis mice.

This observational study is aimed to investigate the quantity and proliferation of Tcm and Tem in the acute phase of sepsis and their correlation with severity level and mortality of septic patients in ICU.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: May 31, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

Patients aged 18-60 years old without restriction of gender, race, religion, creed or nationality; No sedative drugs with elimination half-life were used before inclusion in the study; Patients and/or their family members know and agree to participate in the trial.

Exclusion Criteria:

History of solid organ or bone marrow transplantation; Diseases that may affect immune-related indicators, such as autoimmune diseases such as rheumatoid arthritis and SLE, or hematological malignancies such as leukemia and lymphoma; Have received radiotherapy or chemotherapy within the past 30 days, or have received immunosuppressive drugs (tripterygium, mycophenolate, cyclophosphamide, FK506, etc); Pregnancy or lactation; Chronic nephrosis; Severe chronic liver disease (child-Pugh: Grade C); alcohol or opioid dependence, mental illness, or severe cognitive impairment; Patients and/or their family members refuse to participate in the trial.

Related Conditions & MeSH terms

• Inflammatory Response
• Sepsis
• Toxemia

Locations

Country	Name	City	State
China	Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Wuhan Union Hospital, China

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute number of CD8+T subsets in the peripheral blood (0 hour)	CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells,and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells	0 hour after study inclusion
Primary	Absolute number of CD8+T subsets in the peripheral blood (24 hours)	CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells,and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells	24 hours after study inclusion
Primary	Absolute number of CD8+T subsets in the peripheral blood (48 hours)	CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells,and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells	48 hours after study inclusion
Primary	Absolute number of CD8+T subsets in the peripheral blood (72 hours)	CD3+ CD8+ CCR7+ CD127high CD62L+ CD27high CD45RA- cells,and CD3+ CD8+ CCR7- CD127- CD62L- CD27low CD45RA- cells	72 hours after study inclusion
Primary	proliferation of CD8+T subsets in the peripheral blood (0 hour)	expression of Ki67 in Tcm and Tem	0 hour after study inclusion
Primary	proliferation of CD8+T subsets in the peripheral blood (24 hours)	expression of Ki67 in Tcm and Tem	24 hours after study inclusion
Primary	proliferation of CD8+T subsets in the peripheral blood (48 hours)	expression of Ki67 in Tcm and Tem	48 hours after study inclusion
Primary	proliferation of CD8+T subsets in the peripheral blood (72 hours)	expression of Ki67 in Tcm and Tem	72 hours after study inclusion
Primary	ICU length of stay	Length of stay in the ICU	up to 4 weeks
Primary	PD-1 expression of CD8+T subsets in the peripheral blood (24 hours)	expression of PD-1 in Tcm and Tem	24 hours after study inclusion
Secondary	Mechanical ventilation time after inclusion	Patients requiring mechanical ventilation after study inclusion	up to 4 weeks
Secondary	Total hospital length of stay	Total length of hospital stay	up to 4 weeks
Secondary	In-hospital mortality	Mortality rates for the entire period of hospitalization	up to 4 weeks
Secondary	90-day readmission rate	Percentage of readmission to hospital within 90 days of study inclusion	up to 4 weeks
Secondary	Infection complications	Pulmonary infection, urinary tract infection, bloodstream infections, etc	up to 4 weeks
Secondary	Acute physiology and chronic health evaluation (APACHE) ? score	0-67, higher scores correspond to more severe disease and a higher risk of death	0h after study inclusion
Secondary	Acute physiology and chronic health evaluation (APACHE) ? score	0-67, higher scores correspond to more severe disease and a higher risk of death	24 hours after study inclusion
Secondary	Acute physiology and chronic health evaluation (APACHE) ? score	0-67, higher scores correspond to more severe disease and a higher risk of death	48 hours after study inclusion
Secondary	Acute physiology and chronic health evaluation (APACHE) ? score	0-67, higher scores correspond to more severe disease and a higher risk of death	72 hours after study inclusion
Secondary	Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	0 hour after study inclusion
Secondary	Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	24 hours after study inclusion
Secondary	Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	48 hours after study inclusion
Secondary	Sequential organ failure assessment (SOFA) score	0-43, higher scores correspond to more severe sepsis	72 hours after study inclusion
Secondary	Plasma cytokine levels	IL-2?IL-4?IL-6?IL-10?IL-17A?IFN-??TNF-a	0 hour after study inclusion
Secondary	Plasma cytokine levels	IL-2?IL-4?IL-6?IL-10?IL-17A?IFN-??TNF-a	24 hours after study inclusion
Secondary	Plasma cytokine levels	IL-2?IL-4?IL-6?IL-10?IL-17A?IFN-??TNF-a	48 hours after study inclusion
Secondary	Plasma cytokine levels	IL-2?IL-4?IL-6?IL-10?IL-17A?IFN-??TNF-a	72 hours after study inclusion