Impact of Metabolite Supplementation to Restore Mitochondrial Dysfunction During Septic Shock: a Preclinical Study: MEFDASE Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 55
- 试验地点
- 2
- 主要终点
- Change in mitochondrial metabolism (mitochondrial membrane depolarization and respiration) with the supplementation of metabolite in the cell culture medium
研究概览
简要总结
Septic shock is defined as a subset of sepsis with severe metabolism alterations, leading to organ failure. Septic shock is associated with a high mortality, around 40% according to the SEPSIS 3 definition.
Metabolic alterations are responsible for lactic acidosis, and results in mitochondrial dysfunction.
This study aims at evaluate the impact of exogenous metabolites on restoring mitochondrial function in septic shock patients with lactate acidosis.
Mitochondrial metabolism (quantitative analysis, mitochondrial function) in intact Peripheral Blood Mononuclear Cells (PBMC) will be isolate and analyse from patients at the early phase of septic shock (admission), at day 2 and 4. Participant's medical history will be recorded: renal and liver metabolism, severity scores and outcomes and the need for supportive care in the intensive care unit (ICU) until 28 days after admission.
Furthermore, the investigators will evaluate wether selected metabolites added to the cell culture medium may improve mitochondrial metabolism.
详细描述
In this prospective study, the investigators will include patients admitted to the medical ICU of Angers University Hospital and meeting the SEPSIS-3 criteria for the definition of septic shock (Sequential Organ Failure Assessment (SOFA) score > 2, hyperlactatemia > 2 mmol/L and sepsis).
Blood samples will be collected during the usual care of initial resuscitation and analyzed in the laboratory INSERM (Institut national de la santé et de la recherche médicale) U1232 (University Hospital of Angers).
Mitochondrial metabolism will be analyzed in freshly isolated PBMC and after culture for 1-3 days, with or without the addition of selected metabolites to the cell culture medium.
The evolution of ketogenesis, mitochondrial function, acidobasic status will be assessed across the time (blood samples at day 2 and 4).
Survival, renal and liver metabolism, severity scores and outcomes and the need for supportive care in the intensive care unit (ICU) until 28 days after admission will be recorded.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients aged 18 or more
- •Patients with criteria for septic shock according to SEPSIS 3 definition (presumed sepsis, with persisting hypotension requiring vasopressors to maintain mean arterial pressure > 65 mmHg and having a serum lactate > 2 mmol/L despite adequate fluid expansion).
- •Admitted in the ICU of Angers University Hospital
排除标准
- •Minor patients (aged less 18)
- •Patient subject to legal protection measures
- •Refusal of the patient or his family
- •Preexisting mitochondrial disease
- •Patient with aplasia
- •Pregnant or parturient women
研究组 & 干预措施
Septic shock admitted in Angers' ICU
Patients aged more than 18, admitted in University Hospital of Angers, who meet the full criteria of septic shock
干预措施: Whole blood samples (Biological)
结局指标
主要结局
Change in mitochondrial metabolism (mitochondrial membrane depolarization and respiration) with the supplementation of metabolite in the cell culture medium
时间窗: Day 0 (whole blood after cells separation), Day 1-3 after cell culture
Using Fluorescence-activated cell sorting system to assess the membrane depolarization of the mitochondria and Oroboros system for mitochondrial respiration
次要结局
- Change in organs failure(From Day 0 to Day 4)
- Change and correlation between lactic acidosis, ketogenesis and mitochondrial function evolutions(From Day 1 to Day 3)
- Need for mechanical ventilation during the ICU stay(From Day 1 to Day 28)
- Overall survival at 28 days(Day 28)
- Need for renal replacement therapy during the ICU stay(From Day 1 to Day 28)
- Need for vasopressors during the ICU stay(From Day 1 to Day 28)