Skeletal Muscle Wasting in ICU Patients (IC-MPS)

Muscle wasting occurs rapidly in critically ill patients and impacts both short and long term outcomes. Altered protein metabolism drives muscle loss in ICU patients, with muscle protein breakdown exceeding muscle protein synthesis (MPS). Interventions aimed at attenuating muscle loss by stimulating MPS rates are hampered by a lack of knowledge on altered muscle protein turnover rates during critical illness. Only a few studies have specifically assessed muscle protein synthesis by using contemporary intravenous stable isotope infusions, which allows the assessment of MPS over a short (<9 hours) period of time. Results from such acute studies can be difficult to extend or translate into long-term clinical practice and outcomes. Oral deuterated water (2H2O) dosing provides an alternative method that can be utilized to extend the measurement of muscle protein synthesis over a period of several days or weeks. It could therefore provide a valuable tool to study muscle protein synthesis during ICU admission and the impact of different anabolic interventions. Although multiple studies using the deuterated water methodology have been performed in both healthy volunteers and patients, it has not yet been performed in critically ill patients.

In this prospective study the investigators aim to assess fractional rates of muscle protein synthesis over a period of (maximal) 7 days in critically ill patients admitted to the intensive care unit. Secondly, the investigators aim to assess mechanisms of acute muscle wasting on an microscopic, ultrastructural and molecular level. Furthermore, the investigators aim to investigate to what extent muscle fibre size is recovered 3 months after ICU discharge.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Muscle Atrophy

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Michelle Weijzen, Dr.; Phone Number: 003211268706; Email: michelle.weijzen@uhasselt.be
• Study Contact Backup: Name: Frank Vandenabeele, Prof.; Email: frank.vandenabeele@uhasselt.be

Study Locations

• Belgium
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Recruiting
      • Jessa Hospital
      • Contact: Bjorn Stessel, PhD; Email: bjorn.stessel@jessazh.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

In total 20 patients admitted to the ICU will be included.

Description

Inclusion Criteria:

• age >18y
• admitted to ICU
• enteral nutrition line in situ
• arterial line (any location) in situ
• expected stay ICU >7d

Exclusion Criteria:

• spinal cord injury
• chronic use of corticosteroids before hospital admission
• Contraindication to enteral infusion (e.g. due to GI-tract perforation)
• Kidney or liver failure
• therapeutic anti coagulation

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
muscle protein synthesis rate (%/h)	obtained by using deuterated water, muscle biopsy sampling and blood sampling	7 days of stay at the intensive care unit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
skeletal muscle fiber characteristics 1	cross sectional area of muscle fibers	7 days of stay at the intensive care unit
skeletal muscle fiber characteristics 2	amount and distribution of muscle fibers (distribution will be calculated as: amount of type X / total amount of fibres)	7 days of stay at the intensive care unit
mRNA expression in skeletal muscle tissue 1	mRNA expression in skeletal muscle tissue of MAFBx (atrophy marker)	7 days of stay at the intensive care unit
mRNA expression in skeletal muscle tissue 2	mRNA expression in skeletal muscle tissue of MurF1 (atrophy marker)	7 days of stay at the intensive care unit
mRNA expression in skeletal muscle tissue 3	mRNA expression in skeletal muscle tissue of FOXO (atrophy marker)	7 days of stay at the intensive care unit
patient characteristic- age	age in years	7 days of stay at the intensive care unit
patient characteristic- body weight	body weight in kg	7 days of stay at the intensive care unit
patient characteristic- height	height in m	7 days of stay at the intensive care unit
patient characteristic- sex	male or female	7 days of stay at the intensive care unit
patient characteristics (medical1)	mechanical ventilation (duration in days)	7 days of stay at the intensive care unit
patient characteristics (medical2)	comorbidities (list of comorbidities)	7 days of stay at the intensive care unit
patient characteristics (medical3)	reason hospital admission	7 days of stay at the intensive care unit
patient characteristic- APACHE score II	APACHE II score = acute physiology score + age points + chronic health points. Minimum score = 0; maximum score = 71.	7 days of stay at the intensive care unit
patient characteristic- food intake	food intake (energy in kcal and protein intake in g/kg/d)	7 days of stay at the intensive care unit
patient characteristic- LOS	Length of stay ICU and hospital (in days)	Stay at the intensive care unit and Hospital (up to 1 year)
muscle volume	3d ultrasound assessed at follow up visit	3 months post-hospital discharge
habitual food	Assessed using questionnaires at follow up visit (higher score means better intake)	3 months post-hospital discharge
habitual activity	Assessed using questionnaires at follow up visit (higher score means better intake)	3 months post-hospital discharge
muscle hand grip strength	hand grip strength using the JAMAR dynamometer in kg	3 months post-hospital discharge
leg muscle strength	1RM upper leg at follow up visit	3 months post-hospital discharge
Functional capacity 1	SPPB at follow up visit (short physical performance battery)	3 months post-hospital discharge
Functional capacity 2	6min walking test at follow up visit	3 months post-hospital discharge
Quality of life questionnaire	SF-36 at follow up visit (Short Form Health Survey 36 items) range score between 0-100, lower score represents great health related problems	3 months post-hospital discharge
Quality of life questionnaires	Euro-QoL-5D-5-level at follow up visit (Euro quality of life 5 Dimension 5 level) Answers can be converted into EQ-5D index, an utility scores anchored at 0 for death and 1 for perfect health	3 months post-hospital discharge

Collaborators and Investigators

• Sponsor: Frank Vandenabeele
• Collaborators: Jessa Hospital
• Investigators: Principal Investigator: Frank Vandenabeele, Prof., Hasselt University

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: May 16, 2023
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Estimated): January 31, 2024

Study Record Updates

• Last Update Posted (Estimated): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Disease Attributes; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Muscular Atrophy; Critical Illness
• Other Study ID Numbers: 2022/165

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No