Characterization and Longitudinal Monitoring of Muscular Phenotype in Patients Admitted to Intensive Care for Sepsis.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- MRC score (Medical Research Council).
研究概览
简要总结
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.
详细描述
The care provided to participants enrolled in the study remains unchanged. Standard care is administered. In particular, there are no modifications to routine practices regarding early mobilization, physiotherapy, physical exercise, or nutritional management.
The muscular phenotype of enrolled participants is assessed longitudinally during their ICU stay and after hospital discharge. Several follow-up visits are scheduled:
- Visit 1: Inclusion
- Visit 2: Day 3 (D3)
- Visit 3: Day 7 (D7)
- Visit 4: Day 14 (D14)
- Visit 5: Day 21 (D21)
- Visit 6: Day 28 (D28)
- Visit 7: ICU discharge (may occur before D28)
- Visit 8: Day 90 (D90) - End of study
During these visits, the muscular phenotype is evaluated using non-invasive methods (clinical assessments, ultrasound imaging, and electroneuromyography). Blood samples are collected to determine the inflammatory status of participants and to assess dysfunctions in vital organs.
After the ICU stay, in addition to these data, participants' physical and functional autonomy is documented. Cognitive impairments and symptoms of anxiety and depression are also recorded, along with their nutritional status.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants admitted to ICU with an expected length of stay greater than 7 days.
- •Expected duration of invasive mechanical ventilation greater than 48 hours.
- •Diagnosis of sepsis upon ICU admission (presence of an infection and a SOFA score ≥ 2, or an increase of ≥ 2 points if organ dysfunction was present prior to infection).
- •Informed consent obtained from the participant or from a designated surrogate decision-maker
排除标准
- •Pregnant women.
- •Participants not affiliated with the national health insurance system.
- •Participants under legal protection (guardianship or conservatorship).
- •Moribund participants (end-of-life patients).
- •Participants with active cancer.
- •Participants with chronic neuromuscular disorders or admitted to the ICU for an acute neuromuscular condition.
研究组 & 干预措施
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: Medical Research Council sum score (MRC-SS) test (Diagnostic Test)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: Handgrip test combined with surface electromyography (sEMG) (Diagnostic Test)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: Musculoskeletal Ultrasound (Device)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: Diaphragmatic ultrasound (Device)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: blood sampling (Biological)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: Electrical activity during maximal voluntary contraction of the rectus femoris (Diagnostic Test)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: 6-minute walk test (Diagnostic Test)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: Montreal Cognitive Assessment (MoCA) (Diagnostic Test)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: Electroneuromyogram (Device)
Longitudinal characterization of muscle phenotype in ICU participants with sepsis
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.
干预措施: MNA-SF (Behavioral)
结局指标
主要结局
MRC score (Medical Research Council).
时间窗: From enrollment to the end of the participant's study period (maximum 90 days)
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).
次要结局
- Plasma concentrations of inflammation-related proteins(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))
- Diaphragmatic ultrasound(From enrollment to the end of the participant's study period (maximum 90 days))
- 6-minute walk test(Only during the last visit of the protocol : 90 days after the inclusion)
- Handgrip test combined with surface electromyography (sEMG)(From enrollment to the end of the participant's study period (maximum 90 days))
- Organ dysfunction assesment(From enrollment to the end of the participant's study period (maximum 90 days))
- MNA-SF(Only during the last visit of the protocol : 90 days after the inclusion)
- Musculoskeletal 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)
- Montreal Cognitive Assessment (MoCA)(Only during the last visit of the protocole : 90 days after the inclusion)