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Completed

NCT Number: NCT04099108

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

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.

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Key information

Conditions

Critical Illness Disease Attributes Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Tygerberg Hospital

Cape Town, Western Cape, 7505, South Africa

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Combined cycle ergometry and bolus amino acid supplementation

Combination Product

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.

Primary outcomes

  1. Change in vastus lateralis myofiber cross-sectional area (biopsy) from pre- to post-intervention.

    Time frame: 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).

  2. Change in rectus femoris muscle cross-sectional area (ultrasound) from pre- to post-intervention

    Time frame: 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 outcomes

  1. Change in protein-to-DNA ratio as a secondary marker of muscle mass

    Time frame: From pre- to post-intervention

    Obtained from muscle biopsy of the musculus vastus lateralis of the quadriceps

  2. Signalling pathways for muscle protein synthesis and breakdown

    Time frame: From pre- to post-intervention

    Key proteins regulating muscle protein synthesis and breakdown, including markers of autophagy

  3. 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)

    Time frame: Over shorter intervals from pre-intervention until study exit, if possible (Pre-intervention, Day 5, 7, 10, study exit)

  4. Change in plasma amino acid levels (intervention group only)

    Time frame: 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)

    Based on plasma samples obtained on ICU day 5

  5. Muscle strength

    Time frame: Performed upon ICU awakening, and repeated on ICU discharge and study exit (day 28 or hospital discharge if earlier)

    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)

  6. Physical capability

    Time frame: Performed on study exit only (day 28, or day of hospital discharge if discharged earlier)

    Based on 6-minute walking test

Other outcomes

  1. Change in measured energy expenditure over the first 10 days in ICU

    Time frame: From ICU Day 3+-1 until ICU Day 10+-1, unless contraindicated.

    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)

  2. Assess phase angle (from BIA) as a potential surrogate marker of muscle mass & quality.

    Time frame: Pre- and post-intervention timepoints

    Assess correlation between whole-body phase angle and vastus lateralis myofiber CSA (biopsy), rectus femoris muscle CSA (ultrasound) and rectus femoris echogenicity.

  3. Change in Urea-to-Creatinine Ratio (UCR) over the first 10 days of ICU admission and its correlation with markers of muscle mass

    Time frame: Over first 10 days of ICU admission

    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.

Sponsors and collaborators

Lead sponsor

University of Stellenbosch

Other

Collaborators

  • Fresenius Kabi
  • University of the Western Cape

Registry information

Official study title

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.

Acronym: ProMob-ICU

Important dates

Study start
2021
Primary completion
2022
Study completion
2022
First posted
Sep 23, 2019
Registry last updated
Dec 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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