Enhancing the Anabolic Effect of Nutrition in Critically Ill Patients by Administering Exogenous Amino Acids
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Whole body protein balance
研究概览
简要总结
Enhancing the anabolic effect of nutrition in critically ill patients by administering exogenous amino acids.
详细描述
Critically-ill patients admitted to the intensive care unit are invariably catabolic and are commonly undernourished. Previous observational studies indicate that increased dietary administration of protein or essential amino acids might be associated with improved clinical outcomes. The investigators propose that the parenteral supplementation of intravenous amino acids in critically-ill patients will restore anabolic processes and that anabolism is associated with molecular markers of amino acid sensing and protein synthesis. The results from this study will establish biomarkers of anabolism (i.e., nutritional success) that can be used in future clinical trials on the use of amino acid supplementation in the critically-ill.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •Mechanically ventilated adult patients (>18 years old) admitted to ICU with an expected ICU dependency (alive and need for mechanical ventilation
- •Vasopressor therapy, or mechanical circulatory support) at the point of screening of an additional 3 days, as estimated by the treating physician.
排除标准
- •Patients who are moribund (expected death within 48 hours)
- •Expected to have life-sustaining treatments withdrawn in the next 3 days
- •Those with a contraindication to enteral nutrition (EN)
- •Already on parenteral nutrition (PN)
- •Those with acute fulminant hepatitis or severe chronic liver disease (Child's class C)
- •Patients on extracorporeal membrane oxygenation or carbon dioxide removal* Patients with organ transplantation
- •Those with a broncho-pleural fistula
- •Patients with documented allergies to any of the study nutrients or its excipients will be excluded.
- •Patients requiring continuous renal replacement therapy or extracorporeal membrane oxygenation are excluded due to inability to accurately measure protein turnover.
研究组 & 干预措施
Group 1: Peptamen 1.5% via enteral only
Study patients in this group will be prescribed 1.0 g/kg/d of protein using standard EN Peptamen 1.5%. Based on current compliance or tolerance statistics, investigators expect patients to only receive 50-60% of these prescribed doses; effective protein intake will therefore be approximately 0.5-0.6 g/kg/d
干预措施: Peptamen 1.5% via enteral (Dietary Supplement)
Group 2: Prosol 20% IV to 1.75g/kg/day
Patients in group 2 will receive the same enteral feeding as group 1 (Peptamen 1.5) but in addition will receive sufficient intravenous amino acid supplements (Prosol 20%) to achieve an effective fixed dose of 1.75 g/kg/d
干预措施: Peptamen 1.5% via enteral (Dietary Supplement)
Group 2: Prosol 20% IV to 1.75g/kg/day
Patients in group 2 will receive the same enteral feeding as group 1 (Peptamen 1.5) but in addition will receive sufficient intravenous amino acid supplements (Prosol 20%) to achieve an effective fixed dose of 1.75 g/kg/d
干预措施: Prosol 20% IV to 1.75g/kg/day (Dietary Supplement)
Group 3: Prosol 20% IV to 2.5g/kg/day
Patients in this group will receive intravenous amino acids (Prosol 20%) in addition to standard enteral Peptamen 1.5% to achieve an effective protein intake of 2.5 g/kg/day.
干预措施: Peptamen 1.5% via enteral (Dietary Supplement)
Group 3: Prosol 20% IV to 2.5g/kg/day
Patients in this group will receive intravenous amino acids (Prosol 20%) in addition to standard enteral Peptamen 1.5% to achieve an effective protein intake of 2.5 g/kg/day.
干预措施: Prosol 20% IV to 2.5g/kg/day (Dietary Supplement)
结局指标
主要结局
Whole body protein balance
时间窗: 0 and 48 hours
Primed continuous infusions of stable isotope tracers will be applied to assess dynamic changes in whole body and hepatic protein metabolism (i.e., protein breakdown, amino acid oxidation, protein synthesis, total protein, albumin and fibrinogen synthesis) before 48 hours after beginning the intervention. During the period of isotope infusion, nutrition will be held constant. A positive protein balance (difference between protein synthesis and protein breakdown) will be used as an indicator of whole body anabolism. All isotopes will be purchased from CDN Laboratories (Montreal, Canada). Sterile solutions will be tested to be free of pyrogens. Before beginning each experiment blood and expired air samples will be collected to determine baseline enrichments of \[1-13C\]-ketoisocaproate (\[1-13C\]-KIC), \[6,6-2H2\]glucose, L-\[2H5\]phenylalanine and expired 13CO2. Retention of H13CO3- in the bicarbonate pool will be measured in each patient using the approach of Kien.
次要结局
- Synthesis rates of hepatic secretory proteins (the total plasma protein pool, albumin, fibrinogen in %/d)(0 and 48 hours)
- Metabolic Substrates (micromolar)(0, 24, 36, 48, 72 hours)
- Resting Energy Expenditure (kcal)(0 and 48 hours)
- Biomarker of amino acid restriction or repletion - ELISA (pg/ml)(0, 12, 24, 36, 48, 72 hours)
- Biomarker of amino acid restriction or repletion - mRNA detection (copy number/ml)(0, 12, 24, 36, 48, 72 hours)
- Biomarker of amino acid restriction or repletion - protein levels (fold increase in Western blot band density)(0, 12, 24, 36, 48, 72 hours)
研究者
Arnold Kristof
Doctor
McGill University Health Centre/Research Institute of the McGill University Health Centre