Impact of Metabolite Supplementation to Restore Mitochondrial Dysfunction During Septic Shock: a Preclinical Study

Septic Shock Clinical Trial

— MEFDASE  

Official title:

Impact of Metabolite Supplementation to Restore Mitochondrial Dysfunction During Septic Shock: a Preclinical Study: MEFDASE Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04288635
• Other study ID #: 49RC19_0189
• Status: Recruiting
• Start date: July 9, 2020
• Est. completion date: August 9, 2024

Study information

• Verified date: September 2023
• Source: University Hospital, Angers
• Contact: Julien DEMISELLE, MD
• Phone: +33 2 41 35 58 65
• Email: Julien.Demiselle[@]chu-angers.fr
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 9, 2024
• Est. primary completion date: July 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Organ Failure
• Septic Shock
• Shock
• Shock, Septic

Intervention

Biological:
• Whole blood samples
Whole blood samples at admission, from day one to three after admission

Locations

Country	Name	City	State
France	CHU	Angers	Maine Et Loire

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Angers

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in mitochondrial metabolism (mitochondrial membrane depolarization and respiration) with the supplementation of metabolite in the cell culture medium	Using Fluorescence-activated cell sorting system to assess the membrane depolarization of the mitochondria and Oroboros system for mitochondrial respiration	Day 0 (whole blood after cells separation), Day 1-3 after cell culture
Secondary	Overall survival at 28 days	Survival of patients after ICU admission	Day 28
Secondary	Change in organs failure	Using the Sequential Organ Failure Assessment Score	From Day 0 to Day 4
Secondary	Change and correlation between lactic acidosis, ketogenesis and mitochondrial function evolutions	biochemical analysis of blood samples, assessment of mitochondrial metabolism (quantitative and qualitative analysis).	From Day 1 to Day 3
Secondary	Need for renal replacement therapy during the ICU stay	Need for renal replacement therapy and its duration	From Day 1 to Day 28
Secondary	Need for vasopressors during the ICU stay	Need for vasopressors during the ICU stay and its duration	From Day 1 to Day 28
Secondary	Need for mechanical ventilation during the ICU stay	Need for mechanical ventilation during the ICU stay and its duration	From Day 1 to Day 28