NCT03955887: PNEUMOCHONDRIE

Mitochondrial Dysfunction of Alveolar and Circulating Immune Cells During Acute Respiratory Distress Syndrome: Impact of Infectious Aggression and Alveolar Stretching as a Result of Mechanical Ventilation.

Terminated Last updated 3 February 2026

What this trial tests

trial testing bronchoalveolar lavage fluid (BAL) in Lung Diseases in 28 participants. Terminated before completion.

Timeline

11 June 2019

Primary endpoint
7 May 2020

7 May 2020

Quick facts

Lead sponsor	Centre Hospitalier Universitaire Dijon
Status	Terminated
Study type	OBSERVATIONAL
Enrollment	28
Start date	11 June 2019
Primary completion	7 May 2020
Estimated completion	7 May 2020
Sites	1 location across France

Drugs / interventions tested

• bronchoalveolar lavage fluid (BAL) — full drug profile →
• Venous blood — full drug profile →

Conditions studied

• Lung Diseases — all drugs for Lung Diseases →
• Mechanical Ventilation — all drugs for Mechanical Ventilation →
• Bronchoalveolar Lavage — all drugs for Bronchoalveolar Lavage →

Sponsor

Centre Hospitalier Universitaire Dijon

Who can join

18 and older, any sex, with Lung Diseases or Mechanical Ventilation. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Sepsis leads to a deregulated host response that can lead to organ failure. During sepsis, experimental and clinical data suggest the occurrence of mitochondrial dysfunctions, particularly in circulating muscle and monocytes, which may contribute to organ failure and death.

Lower respiratory infection is the leading cause of death from infectious causes. Mechanical ventilation (MV) is required in 20% of cases of bacterial pneumopathy with Streptococcus pneumoniae (S.p.) , with mortality reaching 50%. There are then frequently criteria for acute respiratory distress syndrome (ARDS), combining bilateral lung involvement and marked hypoxemia.

Cyclic stretching of lung cells induced by MV causes sterile inflammation and tissue damage (i.e. ventilator-induced lung injury \[VILI\]), which can cause cellular dysfunction that alter the immune response, particularly during ARDS. This is why the application of a so-called protective MV is then required. However, this does not prevent about one-third of patients from showing signs of alveolar overdistension, as evidenced by an increase in motor pressure (MP) (MP≥ 15 cmH2O), associated with an increase in mortality.

The deleterious effects of MV could be explained by the occurrence of mitochondrial abnormalities. Indeed, the cyclic stretching of lung cells leads to dysfunction in the respiratory chain and the production of free oxygen radicals (FOS), altering membrane permeability. These phenomena could promote VILI, facilitate the translocation of bacteria from the lung to the systemic compartment and lead to alterations in immune response.

In our model of S.p. pneumopathy in rabbits, animals on MV develop more severe lung disorders (lack of pulmonary clearance of bacteria, bacterial translocation in the blood, excess mortality), compared to animals on spontaneous ventilation (SV). Intracellular pulmonary mitochondrial DNA (mtDNA) concentrations, a reflection of the mitochondrial pool, are significantly decreased in ventilated rabbits compared to SV rabbits and in infected rabbits compared to uninfected rabbits. At the same time, the mitochondrial content of circulating cells decreased early (H8) in all infected rabbits, but was only restored in rabbits in SV, those who survived pneumonia (Blot et al, poster ECCMID 2015, submitted article). These data suggest an alteration in the mechanisms that restore mitochondrial homeostasis (mitochondrial biogenesis and mitophagy) during the dual infection/MV agression, which may explain the observed excess mortality. Other work by our team illustrates the importance of these phenomena by showing in a mouse model of polymicrobial infection that inhibition of mitophagia in macrophages promotes survival (Patoli et al, in preparation). Human data on this subject are non-existent.

The phenomena of mitochondrial dysfunction nevertheless deserve to be explored in humans during the combined MV/pneumopathy aggression in order to understand its possible impact on the effectiveness of the host's immune response. In a personalized medicine approach, these data would open up prospects for targeted therapies, capable of activating mitochondrial biogenesis and/or modulating mitophagia, to prevent organ dysfunction and mortality during severe CALs treated with antibiotic therapy.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. CXCL10 could drive longer duration of mechanical ventilation during COVID-19 ARDS.
   Blot M, Jacquier M, Aho Glele LS, Beltramo G, et al · · 2020 · cited 74× · PMID 33138839 · DOI 10.1186/s13054-020-03328-0
2. The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome.
   Blot M, Bour JB, Quenot JP, Bourredjem A, et al · · 2020 · cited 65× · PMID 33272291 · DOI 10.1186/s12967-020-02646-9
3. Alveolar SARS-CoV-2 Viral Load Is Tightly Correlated With Severity in COVID-19 ARDS.
   Blot M, Jacquier M, Manoha C, Piroth L, et al · · 2021 · cited 20× · PMID 32770223 · DOI 10.1093/cid/ciaa1172