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

Critical Illness Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04099108
• Other study ID #: 001
• Status: Recruiting
• Phase: N/A
• Start date: May 26, 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: January 2022
• Source: University of Stellenbosch
• Contact: Lizl Veldsman
• Phone: 27795202568
• Email: rb[@]sun.ac.za
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2022
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Critical Illness

Intervention

Combination Product:
• Combined cycle ergometry and bolus amino acid supplementation
A 4-hour bolus amino acid supplement administered within 30 minutes after a 30-minute in-bed cycling session.

Locations

Country	Name	City	State
South Africa	Tygerberg Hospital	Cape Town	Western Cape

Sponsors (2)

Lead Sponsor	Collaborator
University of Stellenbosch	Fresenius Kabi

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in myofibre cross-sectional area	Obtained from muscle biopsy of the musculus vastus lateralis of the quadriceps	Over first week in ICU
Primary	Change in muscle fibre cross-sectional area	Bases on ultrasound of the quadriceps femoris muscle	Over first week in ICU
Secondary	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
Secondary	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
Secondary	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
Secondary	Physical capability	Based on 6-minute walking test	Performed between day 7 - 10, and repeated on day 28 of hospital stay, if possible
Secondary	Change in protein to DNA ratio	Obtained from muscle biopsy of the musculus vastus lateralis of the quadriceps	Over first week in ICU
Secondary	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)