Effect of Combined IV Bolus Amino Acid Supplementation and Mobilisation on Muscle Mass in Patients Over the First Week of ICU Care: RCT

Study Overview
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Brief Summary
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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 (in-bed cycling followed by an intravenous bolus amino acid supplement), while the other half will receive standard of care only.

Detailed Description
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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.

Official Title
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The Effect of Combined Intravenous Bolus Amino Acid Supplementation and Mobilisation on Muscle Mass in Critically Ill Patients Over the First Week of ICU Care: a Randomised Controlled Trial.

Conditions
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Critical Illness

Intervention / Treatment
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* Combination Product: Combined cycle ergometry and bolus amino acid supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient (≥18 years) admitted to medical/surgical ICUs 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 - 7 days Expected ICU length of stay of 5 - 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Combined cycle ergometry and bolus amino acid supplementation, along with standard of care | Combination Product: Combined cycle ergometry and bolus amino acid supplementation<br>* A 4-hour bolus amino acid supplement administered within 30 minutes after a 30-minute in-bed cycling session.<br>|
| No Intervention: Control<br>Standard of care only | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in myofibre cross-sectional area | Obtained from muscle biopsy of the musculus vastus lateralis of the quadriceps | Over first week in ICU | 
| Change in muscle fibre cross-sectional area | Bases on ultrasound of the quadriceps femoris muscle | Over first week in ICU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Signalling pathways for muscle protein synthesis and breakdown | Key proteins regulating muscle protein synthesis and breakdown, including markers of autophagy | Over first week in ICU | 
| Change in muscle quality | Muscle echogenicity from ultrasound of quadriceps femoris muscle and phase angle obtained from bio-electrical impedance | Over first week in ICU, and if possible, upon hospital discharge or maximum day 28 of hospital stay | 
| 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 between day 7 - 10, and repeated on day 28 of hospital stay, if possible | 
| Physical capability | Based on 6-minute walking test | Performed between day 7 - 10, and repeated on day 28 of hospital stay, if possible | 
| Change in protein to DNA ratio | Obtained from muscle biopsy of the musculus vastus lateralis of the quadriceps | Over first week in ICU | 
| Change in plasma amino acid levels | Based on blood samples obtained on ICU day 5 | Blood 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) |