Improved Muscle Metabolism by Combination of Muscle Activation and Protein Substitution: a Randomized, Outcome-assessor Blinded, Proof-of-concept Study (IMEMPRO)
概览
- 阶段
- 不适用
- 干预措施
- Dietary Supplement: additional substitution of protein
- 疾病 / 适应症
- ICU Acquired Weakness
- 发起方
- Technical University of Munich
- 入组人数
- 40
- 试验地点
- 8
- 主要终点
- Change in cross sectional area (ΔCSA) of the rectus femoris
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
Intensive Care Unit Acquired Weakness (ICUAW) describes muscle weakness that occurs in around 40% of patients during an intensive care stay. The morbidity and mortality of these patients is significantly increased over a 5-year period. The aim of this study is to investigate the combined effect of early enteral high-protein nutrition and early muscle activation on muscle atrophy in critically ill patients.
The study will include 40 patients (20 intervention, 20 observation) with requirement for enteral nutrition at time of inclusion. In the intervention group the maximum possible level of mobilization is carried out and muscles are activated twice a day using neuromuscular electrical stimulation (NMES). The nutrition plan of the intervention group is based on the applicable guidelines for intensive care medicine with exception of increased protein intake. The control group receives therapy without deviating from the standard according of the DGEM guideline.
The study aims to show that the decrease in muscle mass is significantly less than in the control group (primary hypothesis) via ultrasound of the rectus femoris muscle and in case of given consent muscle biopsy. As secondary hypothesis it is examined whether the combination of early high protein intake and muscle activation improves muscle strength and endurance.
详细描述
Intensive Care Unit Acquired Weakness (ICUAW) describes the clinically diagnosed manifestation of a neuromuscular organ dysfunction. It develops in approximately 40% of all intensive care unit patients amounting to at least 1.2 million patients annually in Germany. All these patients face a broad range of sequeleae and an increased mortality up to 5 years after ICU discharge. A characteristic pathophysiological phenomenon is an early severe muscle atrophy reaching 10% during the first days after ICU admission. The current preventative and therapeutic approach for ICUAW is a combination of targeted risk factor management as well as early activation of muscles, i.e. neuromuscular electrical stimulation (NMES) and early mobilization as they have been shown to counteract the muscle atrophy and mediate different outcome benefits such as shorter ICU stay. Nutrition is a key element of our daily life. Protein intake has been shown to affect lean mass and muscle mass. Research into specific nutritional strategies to treat or prevent ICUAW are scarce and the combination with early muscle activation has not been adequately explored. The study will include 40 patients (20 intervention, 20 observation) who were admitted to an intensive care unit within the last 48 hours. A basic requirement for inclusion is an indication for enteral (via the gastrointestinal tract) nutrition at time of inclusion. In the intervention group, the ability to mobilize is assessed daily and the maximum possible level of mobilization is carried out and additional muscles are activated twice a day using neuromuscular electrical stimulation (NMES). The nutrition plan of the intervention group is based on the applicable guidelines for intensive care medicine. In this study, protein intake is increased in the interventional group. The control group receives therapy without deviating from the standard according to the SOP and DGEM guideline: "Clinical nutrition in intensive care medicine" 2018. The study aims to show that the decrease in muscle mass is significantly less than in the control group (primary hypothesis) via ultrasound of the rectus femoris muscle and muscle biopsy. As a second hypothesis it is examined whether the combination of early high protein intake and muscle activation improves muscle strength and endurance compared to the control group. Further exploratory analyses will investigate changes in the skeletal muscle glycogen content, skeletal muscle histology, skeletal muscle gene expression, skeletal muscle protein level, as well as metabolomic changes in blood and urine. An additional blood sample will be taken after 90 days as part of a follow-up.
研究者
Prof. Dr. Stefan Schaller, MD
Full Professor
Medical University of Vienna
入排标准
入选标准
- •critically ill adults (≥ 18 years of age)
- •newly admitted to the ICU (\<48h)
- •mechanically ventilated, expected to remain for at least 72h
- •enteral nutrition is feasible
排除标准
- •a BMI \> 30
- •expected death or withdrawal of life-sustaining treatments
- •prior neuromuscular disease (e.g. paresis, myopathies, neuropathies)
- •injury or disease preventing neuromuscular electrical stimulation or early mobilization (e.g., elevated intracranial pressure, unstable spine)
- •a pacemaker or other electronic implant
- •allergy to components of NMES adhesive
- •have been dependent during activities of daily living prior to the hospital admission
- •a language barrier
研究组 & 干预措施
Intervention
High protein substitution plus NMES and EM
干预措施: Dietary Supplement: additional substitution of protein
Intervention
High protein substitution plus NMES and EM
干预措施: Neuromuscular electrical stimulation
Intervention
High protein substitution plus NMES and EM
干预措施: Early Mobilization
Control Group
Nutrition and mobilization are carried out according to standard of care.
结局指标
主要结局
Change in cross sectional area (ΔCSA) of the rectus femoris
时间窗: day 1 (study inclusion) and 14 days
Change in muscle mass between study inclusion and study day 14; measured as change of the cross sectional area (ΔCSA) of the rectus femoris muscle via ultrasound.
次要结局
- change in echogenicity of the rectus femoris(day 1 (study inclusion) until 90-day Follow-up)
- change of the pennation angle of the rectus femoris(day 1 (study inclusion) until 90-day Follow-up)
- change in physical physical function(up to 90-day follow-up)
- change in muscle thickness of the rectus femoris(day 1 (study inclusion) until 90-day Follow-up)
- change of the muscle strength, measured by the Medical Research Council score (MRC-score)(day 1 (study inclusion) until 90-day Follow-up)
- change of the muscle strength, measured by handgrip dynamometry(day 1 (study inclusion) until 90-day Follow-up)
- change in muscle endurance(up to 90 day follow up)
- development of quality of life(up to 90-day follow-up)
- change in Skeletal muscle mass(day 1 (study inclusion) until 90-day Follow-up)
- change in extracellular volume(day 1 (study inclusion) until 90-day Follow-up)
- Identify possible predictors of muscle wasting in the blood metabolome at ICU admission(day 1 (study inclusion) until 90-day Follow-up)
- change in the REE (Resting Energy Expenditure)(day 1 (study inclusion) until 90-day Follow-up)
- Identify possible predictors of muscle wasting in urine metabolomics at ICU admission(day 1 (study inclusion) until 90-day Follow-up)
- urea-to-creatinine ratio(day 1 (study inclusion) until 90-day Follow-up)