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| Name | Class |
|---|---|
| Fresenius Kabi | INDUSTRY |
| University Medicine Greifswald | OTHER |
| Berlin Institute of Health | OTHER |
| Universitätsklinikum Ulm |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Experimental | High protein substitution plus NMES and EM |
|
| Control Group | No Intervention | Nutrition and mobilization are carried out according to standard of care. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dietary Supplement: additional substitution of protein | Dietary Supplement | Day one (admission) no nutrition is applied. Protein target is increased as follows:
Additional protein is given within 2 hours after mobilization respectively:
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in cross sectional area (ΔCSA) of the rectus femoris | 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. | day 1 (study inclusion) and 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| change in muscle thickness of the rectus femoris | change in muscle thickness from study inclusion until 90-day follow-up, measured via ultrasound. | day 1 (study inclusion) until 90-day Follow-up |
| change in echogenicity of the rectus femoris |
| Measure | Description | Time Frame |
|---|---|---|
| in-hospital mortality | Mortality during the Hospital stay | until 90-day Follow-up |
| Hospital LOS | Length of stay in the hospital | until 90-day Follow-up |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Stefan J Schaller, MD | Contact | +498941409635 | s.schaller@tum.de | |
| Marian Demitsch | Contact | aai-research@muv.ac.at |
| Name | Affiliation | Role |
|---|---|---|
| Stefan J Schaller, MD | Medical University of Vienna & Charité - Universitätsmedizin Berlin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University of Vienna | Recruiting | Vienna | State of Vienna | 1090 | Austria |
Deidentified data can be requested on reasonable scientific request and data sharing contract, if necessary.
After publication of scientific manuscript.
Deidentified data can be requested on reasonable scientific request and data sharing contract, if necessary.
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| UNKNOWN |
| Medical University of Vienna | OTHER |
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|
| Neuromuscular electrical stimulation | Device | twice daily 60 minutes till day 28 or ICU discharge |
|
| Early Mobilization | Other | at least 20 minutes a day following the SOMS concept. Duration: till 28 day or ICU discharge |
|
change in echogenicity from study inclusion until 90-day follow-up, measured via ultrasound.
| day 1 (study inclusion) until 90-day Follow-up |
| change of the pennation angle of the rectus femoris | change of the pennation angle from study inclusion until 90-day follow-up, measured via ultrasound. | day 1 (study inclusion) until 90-day Follow-up |
| change of the muscle strength, measured by the Medical Research Council score (MRC-score) | change of the muscle strength, measured by the Medical Research Council score (MRC-score) from study inclusion until 90-day follow-up | day 1 (study inclusion) until 90-day Follow-up |
| change of the muscle strength, measured by handgrip dynamometry | change of the muscle strength, measured by handgrip dynamometry from study inclusion until 90-day follow-up | day 1 (study inclusion) until 90-day Follow-up |
| change in muscle endurance | change in muscle endurance, measured by the 6-minute walking test up to 90-day follow-up | up to 90 day follow up |
| change in physical physical function | change in physical physical function, measured by the Short Physical Performance Battery up to 90-day follow-up | up to 90-day follow-up |
| development of quality of life | development of quality of life, measured by the Short Form-36 up to 90-day follow-up | up to 90-day follow-up |
| change in Skeletal muscle mass | change in Skeletal muscle mass, measured with bioelectrical impedance analysis up to 90-day follow-up. | day 1 (study inclusion) until 90-day Follow-up |
| change in extracellular volume | change in extracellular volume, measured by the Body impedance analysis | day 1 (study inclusion) until 90-day Follow-up |
| change in the REE (Resting Energy Expenditure) | change in the REE (Resting Energy Expenditure), measured by indirect calorimetry | day 1 (study inclusion) until 90-day Follow-up |
| urea-to-creatinine ratio | urea-to-creatinine ratio from blood sample | day 1 (study inclusion) until 90-day Follow-up |
| Identify possible predictors of muscle wasting in urine metabolomics at ICU admission | Among the urine metabolomics that will be measured, identify metabolites or combinations of metabolites whose high or low concentration(s) at ICU admission associate(s) with the amount of muscle loss. These metabolites are candidate biomarkers that could be used to identify individuals at risk of large muscle wasting and may give further insights into the mechanisms of muscle wasting. | day 1 (study inclusion) until 90-day Follow-up |
| Identify possible predictors of muscle wasting in the blood metabolome at ICU admission | Among the blood metabolome that will be measured, identify metabolites or combinations of metabolites whose high or low concentration(s) at ICU admission associate(s) with the amount of muscle loss. These metabolites are candidate biomarkers that could be used to identify individuals at risk of large muscle wasting and may give further insights into the mechanisms of muscle wasting. | day 1 (study inclusion) until 90-day Follow-up |
| ICU-LOS | Length of stay in the ICU | until 90-day Follow-up |
| Hospital mortality | Mortality during Hospital stay | until 90-day Follow-up |
| Duration of Mechanical ventilation | Duration of invasive mechanical ventilator dependency | until 90-day Follow-up |
| ICU mortality | Mortality during ICU stay | until 90-day Follow-up |
| enzyme function in the rectus femoris | Spectrophotometry will be done in muscle samples. All samples will be screened for influence of Intensive Care Unit Acquired Weakness (ICUAW) and correlation with blood metabolome changes. | according to biopsy inbetween day 1-7 |
| protein content in the rectus femoris | Western Blot will be done in muscle samples. All samples will be screened for influence of Intensive Care Unit Acquired Weakness (ICUAW) and correlation with blood metabolome changes. | according to biopsy inbetween day 1-7 |
| geneexpression in the rectus femoris | qPCR (quantitive polymerase chain reaction) will be done in muscle samples. All samples will be screened for influence of Intensive Care Unit Acquired Weakness (ICUAW) and correlation with blood metabolome changes. | according to biopsy inbetween day 1-7 |
| Muscle morphology of the rectus femoris | Light-and Electron-Microscopy will be done in muscle samples. All samples will be screened for influence of Intensive Care Unit Acquired Weakness (ICUAW) and correlation with blood metabolome changes. | according to biopsy inbetween day 1-7 |
| Klinikum rechts der Isar, School of Medicine, Technical Universtity of Munich | Active, not recruiting | Munich | Bavaria | 81675 | Germany |
| Charité - Universitätsmedizin Berlin | Active, not recruiting | Berlin | State of Berlin | 10117 | Germany |
| Universitätsklinikum Ulm | Recruiting | Ulm | 89070 | Germany |
|
| ID | Term |
|---|---|
| D009133 | Muscular Atrophy |
| D011502 | Protein-Energy Malnutrition |
| D065308 | Morphological and Microscopic Findings |
| ID | Term |
|---|---|
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D001284 | Atrophy |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D011488 | Protein Deficiency |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D004434 | Early Ambulation |
| ID | Term |
|---|---|
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
| D005791 | Patient Care |
| D013812 | Therapeutics |
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