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

NCT04288635 | Recruiting DMC

• 1 other identifier: 49RC19_0189
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Organ Failure; Septic Shock

Keywords

mitochondrial dysfunction

Outcome Measures

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

  Day 0 (whole blood after cells separation), Day 1-3 after cell culture

Secondary Outcomes (6)

• Overall survival at 28 days

  Day 28

• 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 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

Study Arms (1)

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

Biological: Whole blood samples

Interventions

Whole blood samples BIOLOGICAL

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

Septic shock admitted in Angers' ICU

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (1)

CHU

Angers, Maine et Loire, 49933, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood sample for mitochondrial metabolic assessment, DNA extraction for biogenesis and autophagy genes implication

MeSH Terms

Conditions

Shock, Septic; Multiple Organ Failure; Mitochondrial Diseases

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Julien DEMISELLE, MD

  University Hospital of Angers

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julien DEMISELLE, MD

CONTACT

+33 2 41 35 58 65; Julien.Demiselle@chu-angers.fr

Pierre ASFAR, MD PhD

CONTACT

+33 2 41 35 58 65; PiAsfar@chu-angers.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 28 Days
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2020
• First Posted: February 28, 2020
• Study Start: July 9, 2020
• Primary Completion (Estimated): July 9, 2026
• Study Completion (Estimated): August 9, 2026
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)