Effect of Combined IV Bolus Amino Acid Supplementation and Mobilisation on Skeletal Muscle During the First 10 Days in the ICU: A RCT (ProMob-ICU)

The Effect of Combined Intravenous, Bolus Amino Acid Supplementation and Mobilisation on Skeletal Muscle During the Acute Phase of Critical Illness: a Randomised Controlled Trial.

A single-centre, two-arm, parallel randomised controlled trial (RCT) to compare the combined effect of early intravenous bolus amino acid supplementation and mobilisation versus standard of care on changes in muscle mass over the first week in ICU. Half of study participants will receive the study intervention (an intravenous bolus amino acid supplement combined with in-bed cycling), while the other half will receive standard of care only.

Study Overview

• Status: Completed
• Conditions: Critical Illness
• Intervention / Treatment: Combination product: Combined cycle ergometry and bolus amino acid supplementation

Detailed Description

Critical illness survivors often suffer from severe muscle mass depletion and a profound long-term functional impairment. Hence effective strategies, or a combination of strategies, are needed to reduce skeletal muscle wasting during critical illness. Although amino acids and mobilisation are both known to stimulate the mechanistic target of rapamycin pathway (MTOR) pathway for muscle protein synthesis in healthy adults, there are no trials to date investigating the combined approach of combined cycle ergometry and bolus amino acid supplementation on muscle accretion in the ICU.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7505
      • Tygerberg hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patient (≥18 years) admitted to medical/surgical ICU of Tygerberg Academic Hospital (TBH)
• Expected length of mechanical- or non-invasive ventilation > 48 hours
• Receiving enteral (EN) and/or parenteral nutrition (PN) as per standard care and for a minimum of 5 days
• Expected ICU length of stay of 7 days

Exclusion Criteria:

• Spinal cord lesion or intracranial process associated with muscle weakness
• Acute/chronic degenerative neuromuscular condition
• Fulminant hepatic failure/severe chronic liver disease (MELD score ≥20) or renal failure (based on KDIGO) not on Renal Replacement Therapy
• Untreated thrombosis, or thrombosis where therapeutic levels of anticoagulants have not been reached at the time of inclusion
• Any condition deemed inappropriate by the overseeing doctor- such as precautions or contraindications related to the movement as a result of trauma and/or surgery to the spine, pelvis or lower limbs, or haemodynamic instability.
• Other: imminent death or withdrawal of treatment, pregnancy, lower limb amputation/s or fractures, readmission after previous randomisation, long-term corticosteroid therapy, morbidly obese (BMI ≥ 40kg/m2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Combined cycle ergometry and bolus amino acid supplementation, along with standard of care	Combination product: Combined cycle ergometry and bolus amino acid supplementation; A 4-hour intravenous amino acid bolus combined with 45 minutes of cycle ergometry initiated within 1 hour of initiation of the amino acid supplement, starting on ICU Day 3-4 and given daily for a minimum of 5 days, and until latest Day 10 in the ICU.
No Intervention: Control; Standard of care only (standard care nutrition guided by the ESPEN 2019 guidelines, and routine mobilisation performed as per the local unit's protocols and practice)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in vastus lateralis myofiber cross-sectional area (biopsy) from pre- to post-intervention.	Pre-intervention biopsy performed 1 day before initiating the combined study intervention (on average day 2). Post-intervention biopsy performed after completing 5-days of the combined study intervention (on average day 8).
Change in rectus femoris muscle cross-sectional area (ultrasound) from pre- to post-intervention	Pre-intervention biopsy performed 1 day before initiating the combined study intervention (on average day 2). Post-intervention biopsy performed after completing 5-days of the combined study intervention (on average day 8).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in protein-to-DNA ratio as a secondary marker of muscle mass	Obtained from muscle biopsy of the musculus vastus lateralis of the quadriceps	From pre- to post-intervention
Signalling pathways for muscle protein synthesis and breakdown	Key proteins regulating muscle protein synthesis and breakdown, including markers of autophagy	From pre- to post-intervention
Change in muscle mass (rectus femoris muscle CSA) and quality (RF muscle echogenicity) over shorter intervals from pre-intervention until study exit (Pre-intervention, Day 5, 7, 10, study exit)		Over shorter intervals from pre-intervention until study exit, if possible (Pre-intervention, Day 5, 7, 10, study exit)
Change in plasma amino acid levels (intervention group only)	Based on plasma samples obtained on ICU day 5	Plasma samples will be obtained at 3 time intervals, (1) prior to amino acid infusion (T0), (2) 4 hours post amino acid infusion (T1), and (3) 24 hours post amino acid infusion (T2)
Muscle strength	Overall muscle strength will be evaluated using the Medical Research Council (MRC) sum-score via standardised "manual muscle testing" with each of 12 muscle groups assessed using a 6-point MRC scale and summed to a total score (range: 0 - 60)	Performed upon ICU awakening, and repeated on ICU discharge and study exit (day 28 or hospital discharge if earlier)
Physical capability	Based on 6-minute walking test	Performed on study exit only (day 28, or day of hospital discharge if discharged earlier)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in measured energy expenditure over the first 10 days in ICU	Indirect calorimetry measurements performed as part of standard care nutrition on alternate days from ICU Day 3+-1 until ICU Day 10+-1 in all participants, unless contraindicated, were analysed to assess the change in MEE over time (across the cohort)	From ICU Day 3+-1 until ICU Day 10+-1, unless contraindicated.
Assess phase angle (from BIA) as a potential surrogate marker of muscle mass & quality.	Assess correlation between whole-body phase angle and vastus lateralis myofiber CSA (biopsy), rectus femoris muscle CSA (ultrasound) and rectus femoris echogenicity.	Pre- and post-intervention timepoints
Change in Urea-to-Creatinine Ratio (UCR) over the first 10 days of ICU admission and its correlation with markers of muscle mass	To investigate the effect of the combined intervention, compared with standard care alone, on the change in Urea-to-Creatinine Ratio (UCR) over the first 10 days of ICU admission and to assess the correlation between UCR and biopsy myofiber CSA and ultrasound muscle CSA as markers of muscle mass.	Over first 10 days of ICU admission

Collaborators and Investigators

• Sponsor: University of Stellenbosch
• Collaborators: Fresenius Kabi; University of the Western Cape
• Investigators: Principal Investigator: Lizl Veldsman, M Nutr, University of Stellenbosch

Publications and helpful links

General Publications

• Veldsman L, Lupton-Smith A, Richards GA, Blaauw R: Muscle ultrasound: a reliable bedside tool for dietitians to monitor muscle mass, South Afr J Clin Nutr. 2024:37(3): 125 - 130. doi: 10.1080/16070658.2024.2363707.
• Veldsman L, Richards GA, Lombard C, Blaauw R. Course of measured energy expenditure over the first 10 days of critical illness: A nested prospective study in an adult surgical ICU. Clin Nutr ESPEN. 2025 Feb;65:227-235. doi: 10.1016/j.clnesp.2024.11.009. Epub 2024 Nov 16.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Actual): September 9, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: September 18, 2019
• First Posted (Actual): September 23, 2019

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: critical illness, amino acids, mobilisation, muscle
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Critical Illness
• Other Study ID Numbers: VAMI-001-IP4 (Other Grant/Funding Number: Fresenius Kabi JUMPStart Research Grant)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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