NCT05194631: ECARS

Evaluation of the Regeneration Capacity of Satellite Cells From the Quadriceps Compared to That of the Diaphragm

Completed NA Last updated 6 December 2024

What this trial tests

NA trial testing Quadriceps microbiopsy using a Tru-Cut biopsy needle in Diaphragm Injury in 12 participants. Completed in 30 May 2024.

Timeline

18 February 2022

Primary endpoint
30 May 2024

30 May 2024

Quick facts

Lead sponsor	University Hospital, Montpellier
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	basic science
Enrollment	12
Start date	18 February 2022
Primary completion	30 May 2024
Estimated completion	30 May 2024
Sites	1 location across France

Drugs / interventions tested

• Quadriceps microbiopsy using a Tru-Cut biopsy needle

Conditions studied

• Diaphragm Injury — all drugs for Diaphragm Injury →
• Mechanical Ventilation Complication — all drugs for Mechanical Ventilation Complication →

Sponsor

University Hospital, Montpellier

Who can join

Adults 30 to 80, any sex, with Diaphragm Injury or Mechanical Ventilation Complication. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Actually no treatment exists to prevent the loss of diaphragmatic function induced by mechanical ventilation during an intensive care unit stay. The consequence is a growing number of survivors with moderate to severe chronic respiratory disease so called Ventilation-Induced Diaphragmatic Dysfunction (VIDD). This study complements the BOTAN study (IRB Accreditation number: 198711, NCT02900300) on 24/11/2021 under number 2021\_IRB-MTP\_08-37), which aim was the constitution of a biological bank of diaphragmatic tissue in order to be able to propose an innovative tool for the in vitro screening of bioactive molecules of interest in human, to improve the regenerative capacity of this main and essential muscle for breathing. In this present study, in order to offer this evaluation tool in the screening of bioactive molecules of interest, without the need of the diaphragm biopsy, but simply of the quadriceps, the investigators propose, by adding a quadriceps muscular biopsy to patients already included in BOTAN study, to compare the regenerative capacity of quadriceps and diaphragmatic muscle in the same individual. Thus, this study is the first, which will propose a new minimally invasive tool for the evaluation and optimization of future pharmacological treatments targeted to limit the impact of VIDD.

Thus our main objective of thus study is to compare in the same patient the regenerative capacity of the muscular fiber of the quadriceps to that of the diaphragm in order to set up an in vitro model allowing to test in humans future pharmacological treatment devoted to limit the incidence of VIDD.

In this study will be recruited patients treated surgically for a benign or malignant tumor of the liver requiring surgical excision in contact with the diaphragm and who have agreed to participate in the BOTAN study. The resection to be complete (R0) must pass within the diaphragmatic muscle allowing us to obtain without any constraint for the patient, diaphragmatic tissue.

The provision of 10 samples will enable us to produce the cell cultures needed to achieve the study objectives. In order to take into account subjects who leave the study without meeting the primary endpoint, we plan to include up to 15 subjects.

During this surgery, for the purposes of the present study, the investigators will perform a quadriceps biopsy. Quadriceps biopsies are widely used in biomedical research and no deleterious effects have been described. The surgical team is fully qualified for this type of sampling and all experiments necessary to compare regenerative capacity of quadriceps and diaphragmatic muscular fiber use laboratory techniques perfectly mastered by our research team.

For each patients, this study will be performed over two visits. The first, during a consultation will allow the inclusion of the patient, as well as the collection of clinical data and a second during the scheduled surgical intervention where quadriceps biopsy will be realised. The expected duration of inclusions will be one year.

No immediate individual benefit is expected for the patient. This study aims to improve, in the future, therapies that reduce the incidence of diaphragmatic dysfunction induced by mechanical ventilation. In fact, diaphragmatic dysfunction induced by ventilation is observed in at least 50% of patients in intensive care; this dysfunction has been implicated in the significant lengthening of the hospital stay, the difficulties in weaning from mechanical ventilation and in the increased risk of co-morbidity and mortality. The validation of the first in vitro model in humans of this dysfunction, from quadriceps biopsy, will allow us to pre-select antioxidant molecules and the most effective concentrations to use for a future therapeutic trial aimed at limiting the deleterious effects of mechanical ventilation on the diaphragm in humans.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Targeting mitochondrial quality control: new therapeutic strategies for major diseases.
   Hong WL, Huang H, Zeng X, Duan CY. · · 2024 · cited 38× · PMID 39164792 · DOI 10.1186/s40779-024-00556-1