Improved Muscle Metabolism by Combination of Muscle Activation and Protein Substitution ( IMEMPRO )

NCT ID: NCT05919940

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-27
• Study Completion Date: 2026-01-31

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.

Conditions

ICU Acquired Weakness; Muscle Atrophy; Energy Malnutrition Protein; Quality of Life; Morphological and Microscopic Findings; Metabolic Disturbance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Intervention

High protein substitution plus NMES and EM

Group Type: EXPERIMENTAL

Dietary Supplement: additional substitution of protein

Intervention Type: DIETARY_SUPPLEMENT

Day one (admission) no nutrition is applied.

Protein target is increased as follows:

• to a level of 1,2g/kg/d on day 1 after ICU admission
• to a level of 1,4g/kg/d on day 2 after ICU admission
• to a level of 1,6g/kg/d on day 3 after ICU admission
• to a level of 1,8g/kg/d on day 4 after ICU admission
• to a level of 2,0g/kg/d from day 5 onwoards

Additional protein is given within 2 hours after mobilization respectively:

• to 0,125g/kg/d on day 1 after ICU admission
• to 0,2g/kg/d on day 2 after ICU admission
• to 0,25g/kg/d on day 3 after ICU admission
• to 0,3g/kg/d from day 4 after ICU admission onwoards

Neuromuscular electrical stimulation

Intervention Type: DEVICE

twice daily 60 minutes till day 28 or ICU discharge

Early Mobilization

Intervention Type: OTHER

at least 20 minutes a day following the SOMS concept. Duration: till 28 day or ICU discharge

Control Group

Nutrition and mobilization are carried out according to standard of care.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dietary Supplement: additional substitution of protein

Day one (admission) no nutrition is applied.

Protein target is increased as follows:

• to a level of 1,2g/kg/d on day 1 after ICU admission
• to a level of 1,4g/kg/d on day 2 after ICU admission
• to a level of 1,6g/kg/d on day 3 after ICU admission
• to a level of 1,8g/kg/d on day 4 after ICU admission
• to a level of 2,0g/kg/d from day 5 onwoards

Additional protein is given within 2 hours after mobilization respectively:

• to 0,125g/kg/d on day 1 after ICU admission
• to 0,2g/kg/d on day 2 after ICU admission
• to 0,25g/kg/d on day 3 after ICU admission
• to 0,3g/kg/d from day 4 after ICU admission onwoards

Intervention Type: DIETARY_SUPPLEMENT

Neuromuscular electrical stimulation

twice daily 60 minutes till day 28 or ICU discharge

Intervention Type: DEVICE

Early Mobilization

at least 20 minutes a day following the SOMS concept. Duration: till 28 day or ICU discharge

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fresenius Kabi

INDUSTRY

Sponsor Role: collaborator

University Medicine Greifswald

OTHER

Sponsor Role: collaborator

Berlin Institute of Health

OTHER

Sponsor Role: collaborator

Universitätsklinikum Ulm

UNKNOWN

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Stefan Schaller, MD

Full Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefan J Schaller, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna & Charité - Universitätsmedizin Berlin

Locations

Medical University of Vienna

Vienna, Vienna, Austria

Site Status: RECRUITING

Klinikum rechts der Isar, School of Medicine, Technical Universtity of Munich

Munich, Bavaria, Germany

Site Status: ACTIVE_NOT_RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, Germany

Site Status: RECRUITING

Universitätsklinikum Ulm

Ulm, , Germany

Site Status: RECRUITING

Countries

Austria; Germany

Central Contacts

Stefan J Schaller, MD

Role: CONTACT

s.schaller@tum.de

+498941409635

Kristina Fuest, MD

Role: CONTACT

kristina.fuest@tum.de

Facility Contacts

Stefan J Schaller, MD

Role: primary

stefan.schaller@meduniwien.ac.at

+4314040041020

Study Coordinator

Role: backup

aai-research@meduniwien.ac.at

+4314040041020

Stefan J Schaller, MD

Role: primary

stefan.schaller@charite.de

+49-30-450-531052

Flora Scheffenbichler, MD

Role: primary

flora.scheffenbichler@uni-ulm.de

Bettina Jungwirth, MD

Role: backup

ains@uniklinik- ulm.de

Other Identifiers

IMEMPRO

Identifier Type: -

Identifier Source: org_study_id