Effect of Combined IV Bolus Amino Acid Supplementation and Mobilisation on Muscle Mass in Patients Over the First Week of ICU Care: RCT
- Conditions
- Critical Illness
- Interventions
- Combination Product: Combined cycle ergometry and bolus amino acid supplementation
- Registration Number
- NCT04099108
- Lead Sponsor
- University of Stellenbosch
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 80
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention Combined cycle ergometry and bolus amino acid supplementation Combined cycle ergometry and bolus amino acid supplementation, along with standard of care
- Primary Outcome Measures
Name Time Method Change in myofibre cross-sectional area Over first week in ICU Obtained from muscle biopsy of the musculus vastus lateralis of the quadriceps
Change in muscle fibre cross-sectional area Over first week in ICU Bases on ultrasound of the quadriceps femoris muscle
- Secondary Outcome Measures
Name Time Method Physical capability Performed between day 7 - 10, and repeated on day 28 of hospital stay, if possible Based on 6-minute walking test
Muscle strength Performed between day 7 - 10, and repeated on day 28 of hospital stay, if possible 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)
Change in protein to DNA ratio Over first week in ICU Obtained from muscle biopsy of the musculus vastus lateralis of the quadriceps
Change in muscle quality Over first week in ICU, and if possible, upon hospital discharge or maximum day 28 of hospital stay Muscle echogenicity from ultrasound of quadriceps femoris muscle and phase angle obtained from bio-electrical impedance
Signalling pathways for muscle protein synthesis and breakdown Over first week in ICU Key proteins regulating muscle protein synthesis and breakdown, including markers of autophagy
Change in plasma amino acid levels 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) Based on blood samples obtained on ICU day 5
Trial Locations
- Locations (1)
Tygerberg Hospital
🇿🇦Cape Town, Western Cape, South Africa