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

NCT04099108 | Completed DMC

• 1 other identifier: VAMI-001-IP4
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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 (an intravenous bolus amino acid supplement combined with in-bed cycling), while the other half will receive standard of care only.

Conditions

Critical Illness

Keywords

critical illness, amino acids, mobilisation, muscle

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

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

  From pre- to post-intervention

• Signalling pathways for muscle protein synthesis and breakdown

  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)

  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

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

Other Outcomes (3)

• Change in measured energy expenditure over the first 10 days in ICU

  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.

  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

  Over first 10 days of ICU admission

Study Arms (2)

Intervention

EXPERIMENTAL

Combined cycle ergometry and bolus amino acid supplementation, along with standard of care

Combination Product: Combined cycle ergometry and bolus amino acid supplementation

Control

NO INTERVENTION

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)

Interventions

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.

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University of Stellenbosch: lead
• Fresenius Kabi: collaborator
• University of the Western Cape: collaborator

Study Sites (1)

Tygerberg Hospital

Cape Town, Western Cape, 7505, South Africa

Location

Related Publications (2)

• 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.

  RESULT

• 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.

  PMID: 39551349 RESULT

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lizl Veldsman, M Nutr

  University of Stellenbosch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Owing to the nature of the intervention, blinding of participants and treating clinicians was not feasible. However, blinding was maintained for primary outcome assessments, namely: (1) laboratory personnel responsible for biopsy analyses were blinded to group allocation, and (2) ultrasound image analysis was conducted by a blinded assessor. Furthermore, investigators responsible for secondary outcome measures with a subjective component, i.e., MRC sum score and 6MWT assessment, were blinded. Recognising the importance of clearly reporting blinding procedures in RCTs to enhance internal validity and adhere to CONSORT recommendations, the following measures were implemented: * The combined study intervention was performed in the morning, and outcome assessments were blinded in the afternoon with a sufficient interval to avoid overlapping. * The participants were prompted not to disclose their perceptions of group allocation during the outcome assessments.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 23, 2019
• Study Start: May 24, 2021
• Primary Completion: September 9, 2022
• Study Completion: December 31, 2022
• Last Updated: December 3, 2025

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1)