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

Primary Purpose

ICU Acquired Weakness, Muscle Atrophy, Energy Malnutrition Protein

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Dietary Supplement: additional substitution of protein
Neuromuscular electrical stimulation
Early Mobilization
Sponsored by
Technical University of Munich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for ICU Acquired Weakness focused on measuring Early Mobilization and high-protein nutrition

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Klinikum rechts der Isar, School of Medicine, Technical Universtity of Munich
  • Charité - Universitätsmedizin BerlinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intervention

Control Group

Arm Description

High protein substitution plus NMES and EM

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

change in muscle thickness of the rectus femoris
change in muscle thickness from study inclusion until 90-day follow-up, measured via ultrasound.
change in echogenicity of the rectus femoris
change in echogenicity from study inclusion until 90-day follow-up, measured via ultrasound.
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.
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
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
change in muscle endurance
change in muscle endurance, measured by the 6-minute walking test 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
development of quality of life
development of quality of life, measured by the Short Form-36 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.
change in extracellular volume
change in extracellular volume, measured by the Body impedance analysis
change in the REE (Resting Energy Expenditure)
change in the REE (Resting Energy Expenditure), measured by indirect calorimetry
urea-to-creatinine ratio
urea-to-creatinine ratio from blood sample
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.
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.

Full Information

First Posted
June 6, 2023
Last Updated
July 6, 2023
Sponsor
Technical University of Munich
Collaborators
Fresenius Kabi, University Medicine Greifswald, Berlin Institute of Health
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1. Study Identification

Unique Protocol Identification Number
NCT05919940
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 27, 2023 (Actual)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
January 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Technical University of Munich
Collaborators
Fresenius Kabi, University Medicine Greifswald, Berlin Institute of Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ICU Acquired Weakness, Muscle Atrophy, Energy Malnutrition Protein, Quality of Life, Morphological and Microscopic Findings, Metabolic Disturbance
Keywords
Early Mobilization and high-protein nutrition

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
High protein substitution plus NMES and EM
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
Nutrition and mobilization are carried out according to standard of care.
Intervention Type
Dietary Supplement
Intervention Name(s)
Dietary Supplement: additional substitution of protein
Intervention Description
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
Device
Intervention Name(s)
Neuromuscular electrical stimulation
Intervention Description
twice daily 60 minutes till day 28 or ICU discharge
Intervention Type
Other
Intervention Name(s)
Early Mobilization
Intervention Description
at least 20 minutes a day following the SOMS concept. Duration: till 28 day or ICU discharge
Primary Outcome Measure Information:
Title
Change in cross sectional area (ΔCSA) of the rectus femoris
Description
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.
Time Frame
day 1 (study inclusion) and 14 days
Secondary Outcome Measure Information:
Title
change in muscle thickness of the rectus femoris
Description
change in muscle thickness from study inclusion until 90-day follow-up, measured via ultrasound.
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
change in echogenicity of the rectus femoris
Description
change in echogenicity from study inclusion until 90-day follow-up, measured via ultrasound.
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
change of the pennation angle of the rectus femoris
Description
change of the pennation angle from study inclusion until 90-day follow-up, measured via ultrasound.
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
change of the muscle strength, measured by the Medical Research Council score (MRC-score)
Description
change of the muscle strength, measured by the Medical Research Council score (MRC-score) from study inclusion until 90-day follow-up
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
change of the muscle strength, measured by handgrip dynamometry
Description
change of the muscle strength, measured by handgrip dynamometry from study inclusion until 90-day follow-up
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
change in muscle endurance
Description
change in muscle endurance, measured by the 6-minute walking test up to 90-day follow-up
Time Frame
up to 90 day follow up
Title
change in physical physical function
Description
change in physical physical function, measured by the Short Physical Performance Battery up to 90-day follow-up
Time Frame
up to 90-day follow-up
Title
development of quality of life
Description
development of quality of life, measured by the Short Form-36 up to 90-day follow-up
Time Frame
up to 90-day follow-up
Title
change in Skeletal muscle mass
Description
change in Skeletal muscle mass, measured with bioelectrical impedance analysis up to 90-day follow-up.
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
change in extracellular volume
Description
change in extracellular volume, measured by the Body impedance analysis
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
change in the REE (Resting Energy Expenditure)
Description
change in the REE (Resting Energy Expenditure), measured by indirect calorimetry
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
urea-to-creatinine ratio
Description
urea-to-creatinine ratio from blood sample
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
Identify possible predictors of muscle wasting in urine metabolomics at ICU admission
Description
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.
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Title
Identify possible predictors of muscle wasting in the blood metabolome at ICU admission
Description
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.
Time Frame
day 1 (study inclusion) until 90-day Follow-up
Other Pre-specified Outcome Measures:
Title
in-hospital mortality
Description
Mortality during the Hospital stay
Time Frame
until 90-day Follow-up
Title
Hospital LOS
Description
Length of stay in the hospital
Time Frame
until 90-day Follow-up
Title
ICU-LOS
Description
Length of stay in the ICU
Time Frame
until 90-day Follow-up
Title
Hospital mortality
Description
Mortality during Hospital stay
Time Frame
until 90-day Follow-up
Title
Duration of Mechanical ventilation
Description
Duration of invasive mechanical ventilator dependency
Time Frame
until 90-day Follow-up
Title
ICU mortality
Description
Mortality during ICU stay
Time Frame
until 90-day Follow-up
Title
enzyme function in the rectus femoris
Description
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.
Time Frame
according to biopsy inbetween day 1-7
Title
protein content in the rectus femoris
Description
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.
Time Frame
according to biopsy inbetween day 1-7
Title
geneexpression in the rectus femoris
Description
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.
Time Frame
according to biopsy inbetween day 1-7
Title
Muscle morphology of the rectus femoris
Description
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.
Time Frame
according to biopsy inbetween day 1-7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Stefan J Schaller, MD
Phone
+498941409635
Email
s.schaller@tum.de
First Name & Middle Initial & Last Name or Official Title & Degree
Kristina Fuest, MD
Email
kristina.fuest@tum.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefan J Schaller, MD
Organizational Affiliation
TUM, Germany & Charité - Universitätsmedizin Berlin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Klinikum rechts der Isar, School of Medicine, Technical Universtity of Munich
City
Munich
State/Province
Bavaria
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristina Fuest, MD
Email
kristina.fuest@tum.de
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan J Schaller, MD
Phone
+49-30-450-531052
Email
stefan.schaller@charite.de

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified data can be requested on reasonable scientific request and data sharing contract, if necessary.
IPD Sharing Time Frame
After publication of scientific manuscript.
IPD Sharing Access Criteria
Deidentified data can be requested on reasonable scientific request and data sharing contract, if necessary.

Learn more about this trial

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

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