Impact of Metabolite Supplementation to Restore Mitochondrial Dysfunction During Septic Shock: a Preclinical Study
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Whole blood samples.
- Who it may be relevant to
- Registry conditions: Septic Shock, Multiple Organ Failure. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Impact of Metabolite Supplementation to Restore Mitochondrial Dysfunction During Septic Shock: a Preclinical Study: MEFDASE Study
Overview
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.
Detailed description
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.
Interventions
- Biological Whole blood samples
Whole blood samples at admission, from day one to three after admission
Primary outcome measures
- Change in mitochondrial metabolism (mitochondrial membrane depolarization and respiration) with the supplementation of metabolite in the cell culture medium [Time frame: Day 0 (whole blood after cells separation), Day 1-3 after cell culture]
Secondary outcome measures (6)
- Overall survival at 28 days [Time frame: Day 28]
- Change in organs failure [Time frame: From Day 0 to Day 4]
- Change and correlation between lactic acidosis, ketogenesis and mitochondrial function evolutions [Time frame: From Day 1 to Day 3]
- Need for renal replacement therapy during the ICU stay [Time frame: From Day 1 to Day 28]
- Need for vasopressors during the ICU stay [Time frame: From Day 1 to Day 28]
- Need for mechanical ventilation during the ICU stay [Time frame: From Day 1 to Day 28]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 1 center
- CHU — Angers
Identifiers
NCT: NCT04288635 · 49RC19_0189