Metabolism of Branched-chain Amino Acids in Monocyte/Macrophage During Sepsis

Metabolism of Branched-chain Amino Acids in Monocyte and Macrophage During Sepsis

The current project was designed to examine the metabolic level of branched-chain amino acids in plasm and monocyte/macrophage, and its role in immune dysfunction during sepsis.

Study Overview

• Status: Unknown
• Conditions: Sepsis Syndrome
• Intervention / Treatment: Other: Metabolic level of BCAAs in monocytes and macrophages

Detailed Description

In this study, the investigators will collect the peripheral blood of 1,3,7,14 day after diagnose of sepsis. Then, the concentration of branched-chain amino acids(BCAAs) in monocytes and plasma, and the expression of BCAAs metabolic enzymes in monocytes will be determined. Additionally, the inflammatory cytokines, e.g., Interleukin-1β (IL-1β), Tumor necrosis factor-α (TNF-α), Interleukin-10 (IL-10）, the chemokines macrophage inflammatory proteins 1α and 1β (MIP-1α and 1β) in the peripheral blood and the phagocytic function of monocytes will also be detected. The current project was designed to examine the metabolic level of branched-chain amino acids in plasm and monocyte/macrophage, and its role in immune dysfunction during sepsis.

• Study Type: Observational
• Enrollment (Anticipated): 90

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients who are diagnosed as sepsis, with or without type 2 diabetes.

Description

Inclusion Criteria:

• patients diagnosed with sepsis, with or without type 2 diabetes
• healthy volunteers

Exclusion Criteria:

• patients with immunodeficient diseases
• patients who accept glucocorticoid or immunosuppressant
• patients with an age younger than 18 years
• patients who cannot provide the informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sepsis with type 2 diabetes; Sepsis patients with type 2 diabetes	Other: Metabolic level of BCAAs in monocytes and macrophages; Metabolic level of BCAAs in monocytes and macrophages
Sepsis without type 2 diabetes; Sepsis patients without type 2 diabetes	Other: Metabolic level of BCAAs in monocytes and macrophages; Metabolic level of BCAAs in monocytes and macrophages
Volunteers; Healthy volunteers	Other: Metabolic level of BCAAs in monocytes and macrophages; Metabolic level of BCAAs in monocytes and macrophages

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracellular levels of branched-chain amino acids in monocytes	BCAAs Assay Kit will be used to measure the intracellular levels of BCAAs in monocytes.	up to 14 day after diagnose of sepsis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels of branched-chain amino acids	BCAAs Assay Kit will be used to measure the plasma levels of BCAAs.	1,3,5,7,10,14 day after diagnose of sepsis
The expression of branched-chain amino acid aminotransferase in monocytes	The expression of branched-chain amino acid aminotransferase in monocytes will be determined by qPCR and western blot.	1,3,5,7,10,14 day after diagnose of sepsis
The expression of branched-chain α-ketoacid dehydrogenase in monocytes	The expression of branched-chain α-ketoacid dehydrogenase in monocytes will be determined by qPCR and western blot.	1,3,5,7,10,14 day after diagnose of sepsis
The expression of PP2Cm in monocytes	The expression of mitochondrial-targeted phosphatase, PP2Cm in monocytes will be determined by qPCR and western blot.	1,3,5,7,10,14 day after diagnose of sepsis
The plasma level of IL-1β	The plasma level of IL-1β will be determined by ELISA kit.	1,3,5,7,10,14 day after diagnose of sepsis.
The plasma level of TNF-α	The plasma level of TNF-α will be determined by ELISA kit.	1,3,5,7,10,14 day after diagnose of sepsis.
The plasma level of IL-10	The level of IL-10 will be determined by ELISA kit.	1,3,5,7,10,14 day after diagnose of sepsis.
The plasma level of chemokine MIP-1α.	The plasma level of chemokine MIP-1α will be determined by ELISA kit.	1,3,5,7,10,14 day after diagnose of sepsis.
The plasma level of chemokine MIP-1β.	The plasma level of chemokine MIP-1β will be determined by ELISA kit.	1,3,5,7,10,14 day after diagnose of sepsis.
The phagocytic index of monocytes.	The phagocytic index of monocytes will be determined by a E.coli Phagocytosis Assay Kit.	1,3,5,7,10,14 day after diagnose of sepsis.

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 11, 2019
• Primary Completion (Anticipated): December 30, 2021
• Study Completion (Anticipated): February 28, 2022

Study Registration Dates

• First Submitted: February 8, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 14, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Shock; Sepsis; Toxemia; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: 2018-081 (Registry Identifier: METC ErasmusMC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No