Clinical trial NCT05919940: Improved Muscle Metabolism by Combination of Muscle Activation and Protein Substitution ( IMEMPRO )
Official title: Improved Muscle Metabolism by Combination of Muscle Activation and Protein Substitution: a Randomized, Outcome-assessor Blinded, Proof-of-concept Study (IMEMPRO)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: ICU Acquired Weakness
Muscle Atrophy
Energy Malnutrition Protein
Quality of Life
Morphological and Microscopic Findings
Metabolic Disturbance
Keywords: Early Mobilization and high-protein nutrition
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
Collaborators: name: Fresenius Kabi
name: University Medicine Greifswald
name: Berlin Institute of Health
name: Universitätsklinikum Ulm
First posted: 2023-06-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in cross sectional area (ΔCSA) of the rectus femoris
timeFrame: day 1 (study inclusion) and 14 days
Secondary outcomes:
measure: change in muscle thickness of the rectus femoris
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: change in echogenicity of the rectus femoris
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: change of the pennation angle of the rectus femoris
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: change of the muscle strength, measured by the Medical Research Council score (MRC-score)
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: change of the muscle strength, measured by handgrip dynamometry
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: change in muscle endurance
timeFrame: up to 90 day follow up
measure: change in physical physical function
timeFrame: up to 90-day follow-up
measure: development of quality of life
timeFrame: up to 90-day follow-up
measure: change in Skeletal muscle mass
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: change in extracellular volume
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: change in the REE (Resting Energy Expenditure)
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: urea-to-creatinine ratio
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: Identify possible predictors of muscle wasting in urine metabolomics at ICU admission
timeFrame: day 1 (study inclusion) until 90-day Follow-up
measure: Identify possible predictors of muscle wasting in the blood metabolome at ICU admission
timeFrame: day 1 (study inclusion) until 90-day Follow-up
Other outcomes:
measure: in-hospital mortality
timeFrame: until 90-day Follow-up
measure: Hospital LOS
timeFrame: until 90-day Follow-up
measure: ICU-LOS
timeFrame: until 90-day Follow-up
measure: Hospital mortality
timeFrame: until 90-day Follow-up
measure: Duration of Mechanical ventilation
timeFrame: until 90-day Follow-up
measure: ICU mortality
timeFrame: until 90-day Follow-up
measure: enzyme function in the rectus femoris
timeFrame: according to biopsy inbetween day 1-7
measure: protein content in the rectus femoris
timeFrame: according to biopsy inbetween day 1-7
measure: geneexpression in the rectus femoris
timeFrame: according to biopsy inbetween day 1-7
measure: Muscle morphology of the rectus femoris
timeFrame: according to biopsy inbetween day 1-7
Locations:
city: Munich
country: Germany
facility: Klinikum rechts der Isar, School of Medicine, Technical Universtity of Munich
state: Bavaria
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
Study officials:
affiliation: TUM, Germany & Charité - Universitätsmedizin Berlin
name: Stefan J Schaller, MD
role: PRINCIPAL_INVESTIGATOR
References: