Impact of Metabolite Supplementation to Restore Mitochondrial Dysfunction During Septic Shock: a Preclinical Study
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity Hospital, Angers
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Minor patients (aged less 18)
Patient subject to legal protection measures
Refusal of the patient or his family
Preexisting mitochondrial disease
Trial population
All patients aged 18 or more who meet the SEPSIS-3 criteria for septic shock : a 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 to the medical ICU of Angers University Hospital.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Whole blood samples
Biological/VaccineWhole blood samples at admission, from day one to three after admission
Treatment groups
55 Participants
are divided into 1 treatment groupGroup A: Septic shock admitted in Angers' ICU1 intervention
Trial outcomes
Primary outcomes
1
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
Time frame
Day 0 (whole blood after cells separation), Day 1-3 after cell cultureSecondary outcomes
1
Overall survival at 28 days
Survival of patients after ICU admission
Time frame
Day 282
Change in organs failure
Using the Sequential Organ Failure Assessment Score
Time frame
From Day 0 to Day 43
Change and correlation between lactic acidosis, ketogenesis and mitochondrial function evolutions
biochemical analysis of blood samples, assessment of mitochondrial metabolism (quantitative and qualitative analysis).
Time frame
From Day 1 to Day 34
Need for renal replacement therapy during the ICU stay
Need for renal replacement therapy and its duration
Time frame
From Day 1 to Day 28Sponsors and contacts
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Source ClinicalTrials.gov