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.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Change in rectus femoris muscle cross-sectional area (ultrasound) from pre- to post-intervention
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
结局指标
主要结局
Change in rectus femoris muscle cross-sectional area (ultrasound) from pre- to post-intervention
时间窗: 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 vastus lateralis myofiber cross-sectional area (biopsy) from pre- to post-intervention.
时间窗: 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
时间窗: 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).
次要结局
- 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)
- Muscle strength(Performed upon ICU awakening, and repeated on ICU discharge and study exit (day 28 or hospital discharge if earlier))
- Physical capability(Performed on study exit only (day 28, or day of hospital discharge if discharged earlier))
- 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))
- Physical capability(Performed on study exit only (day 28, or day of hospital discharge if discharged earlier))
研究者
Prof Renee Blaauw
Professor
University of Stellenbosch