Brief Summary

Approximately 40% of patients develop muscle dysfunction during their stay in intensive care, particularly in the context of sepsis. This dysfunction represents an acquired muscle injury that is secondary to the primary illness that led to ICU admission. It affects both the limb muscles and the respiratory muscles of the thoracic cage. Clinically, this manifests as bilateral and symmetrical muscle weakness in the limbs, and contributes significantly to difficulties in weaning patients off mechanical ventilation. The loss of muscle mass is directly correlated with the severity of the patient's clinical condition and can reach up to 20% of initial muscle mass within just ten days. This rapid and profound atrophy primarily results from an imbalance between increased muscle protein breakdown (catabolism) and insufficient protein synthesis (anabolism). The consequences of this muscle dysfunction are significant and far-reaching, with a marked negative impact on the overall prognosis. This condition is associated with longer durations of mechanical ventilation and extended stays in the intensive care unit. Beyond the acute phase, patients often experience persistent reductions in physical performance, leading to long-term functional limitations that impair quality of life. Furthermore, ICU-acquired muscle dysfunction has been linked to increased long-term mortality, with excess deaths reported at both one year and five years following ICU discharge. This risk is especially pronounced when the muscle dysfunction is severe and continues beyond the hospitalization period. Several risk factors for ICU-acquired muscle dysfunction may be modifiable, opening up the possibility for preventive or therapeutic interventions. Two main factors have been identified as particularly relevant: (1) the duration of immobility and muscular inactivity, and (2) the adequacy of nutritional support, especially regarding amino acid intake, which is critical for maintaining muscle protein synthesis. In response to these factors, early and active mobilization of ICU patients has become a key component of recommended care, often in conjunction with strategies aimed at minimizing the use of sedative medications. These practices are encouraged by international guidelines, reflecting a growing consensus around the importance of maintaining some level of muscular activity even in critically ill patients. However, despite these recommendations, no definitive evidence has demonstrated a clear improvement in patient outcomes associated with early mobilization. This lack of clear benefit may stem from multiple factors, including the variability in patient severity across clinical trials and, importantly, the timing of the intervention. The anabolic signals triggered by muscle contraction are only effective if they are strong enough to counterbalance the catabolic signals driven by inflammation, infection, or muscle hypoxia-all of which fluctuate over the course of illness and recovery. Regarding nutritional interventions, the appropriate timing and quantity of calorie and protein intake necessary to support adequate anabolism and mitigate muscle loss remain controversial. Although amino acids are essential for muscle protein synthesis, current studies have not shown consistent improvements in muscle function based on different nutritional strategies in the ICU setting. Given the high prevalence of ICU-acquired muscle dysfunction in patients with sepsis, its significant impact on outcomes, and the lack of an effective, evidence-based treatment, there is a pressing need to deepen our scientific understanding of this phenomenon. Improving knowledge in this area could lead to more targeted and effective interventions, ultimately helping to preserve muscle mass and function in critically ill patients and improving both their short- and long-term prognosis.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for not_applicable sepsis

Timeline

13mo left

Started Mar 2025

Typical duration for not_applicable sepsis

Geographic Reach

1 country

1 active site

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

2.3 years study duration

Study Progress50%

Mar 2025Jun 2027

Study Start

First participant enrolled

March 25, 2025

Completed

3 months until next milestone

First Submitted

Initial submission to the registry

June 19, 2025

Completed

1 month until next milestone

First Posted

Study publicly available on registry

July 20, 2025

Completed

1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 25, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 25, 2027

Last Updated

July 20, 2025

Status Verified

July 1, 2025

Enrollment Period

2.3 years

First QC Date

June 19, 2025

Last Update Submit

July 17, 2025

Conditions

Sepsis Myopathy Critical Illness

Keywords

muscle atrophyelectromyographyMuscle Strengthconditioned medium with human serum

Outcome Measures

Primary Outcomes (1)

MRC score (Medical Research Council).
The MRC score allows for a global assessment of muscle function in ICU patients. An MRC score below 48, measured on day 28 or at ICU discharge (if discharge occurs before day 28), defines ICU-acquired weakness (ICU-AW).
From enrollment to the end of the participant's study period (maximum 90 days)

Secondary Outcomes (10)

Handgrip test combined with surface electromyography (sEMG)
From enrollment to the end of the participant's study period (maximum 90 days)
Electrical activity during maximal voluntary contraction of the rectus femoris
From enrollment to the end of the participant's study period (maximum 90 days)
Musculoskeletal Ultrasound
From enrollment to the end of the participant's study period (maximum 90 days)
Diaphragmatic ultrasound
From enrollment to the end of the participant's study period (maximum 90 days)
Electroneuromyogram
Only during the last visit of the protocol : 90 days after the inclusion
+5 more secondary outcomes

Study Arms (1)

Longitudinal characterization of muscle phenotype in ICU participants with sepsis

EXPERIMENTAL

Through successive visits during and after the ICU stay, the muscle phenotype of participants is determined using non-invasive data collection methods (clinical assessments, ultrasound imaging, and electroneuromyography). Blood samples are harvested to assess the participants' inflammatory status and evaluate organ dysfunction. Following the ICU stay, in addition to the previously mentioned data, participants' physical and functional autonomy is assessed. Cognitive impairments and symptoms of anxiety and depression are also recorded, along with their nutritional status.

Diagnostic Test: Medical Research Council sum score (MRC-SS) testDiagnostic Test: Handgrip test combined with surface electromyography (sEMG)Diagnostic Test: Electrical activity during maximal voluntary contraction of the rectus femorisDevice: Musculoskeletal UltrasoundDevice: Diaphragmatic ultrasoundBiological: blood samplingDevice: ElectroneuromyogramDiagnostic Test: 6-minute walk testDiagnostic Test: Montreal Cognitive Assessment (MoCA)Behavioral: MNA-SF

Interventions

Medical Research Council sum score (MRC-SS) testDIAGNOSTIC_TEST

Medical Research Council (MRC)-sumscore evaluates global muscle strength. Manual strength of six muscle groups (shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion) is evaluated on both sides using MRC scale