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Enhancing the anabolic effect of nutrition in critically ill patients by administering exogenous amino acids.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Peptamen 1.5% via enteral only | Active Comparator | 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 |
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| Group 2: Prosol 20% IV to 1.75g/kg/day | Active Comparator | 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 |
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| Group 3: Prosol 20% IV to 2.5g/kg/day | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Peptamen 1.5% via enteral | Dietary Supplement | Study patients in this group will be prescribed 1.0 g/kg/d of protein using standard enteral 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Whole body protein balance | 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. | 0 and 48 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Synthesis rates of hepatic secretory proteins (the total plasma protein pool, albumin, fibrinogen in %/d) | This will be measured from the rates of incorporation of L-[2H5] phenylalanine into the proteins using plasma very low density lipoprotein apolipoprotein-B100 (VLDL-apoB-100) isotopic enrichment at plateau to represent the isotopic enrichment of the phenylalanine precursor pool from which the liver synthesizes the other plasma protein. A priming dose of L-[2H5]phenylalanine (4 μmol/kg, iv) will be given followed by a six-hour infusion at 0.10 μmol/kg/min. At baseline, 3 hours, 4 hours, 5 hours, and 6 hours thereafter blood will be drawn, immediately transferred into pre-chilled tubes containing Na2EDTA and a protease inhibitor cocktail of sodium azide, merthiolate and soybean trypsin inhibitor, then centrifuged and stored at -70ºC for later analysis. 10 ml blood will be required for secretory protein synthesis studies. |
| Measure | Description | Time Frame |
|---|---|---|
| ICU length of stay | Duration of ICU admission in days. | 72 hours to 1 year |
| Hospital length of stay | Duration of ICU admission in days. | 72 hours to 1 year |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Arnold S Kristof, MDCM, FRCPC | McGill University Health Centre/Research Institute of the McGill University Health Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McGill University health Centre | Montreal | Quebec | H4A 3J1 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40617772 | Derived | Kristof AS, Hong M, Boufaied N, Tousson-Abouelazm N, Dandamudi S, Joung KB, Hatzakorzian R, Port M, Campisi G, Piccirillo CA, Fonseca GJ, Ding J, Heyland DK, Labbe DP, Wykes L, Schricker T. Biological responses during high-dose protein nutrition in the critically ill: a randomized controlled trial. Am J Clin Nutr. 2025 Aug;122(2):612-623. doi: 10.1016/j.ajcnut.2025.05.025. Epub 2025 Jun 26. | |
| 34920728 |
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| ID | Term |
|---|---|
| D016638 | Critical Illness |
| D007249 | Inflammation |
| D044342 | Malnutrition |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009748 | Nutrition Disorders |
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| ID | Term |
|---|---|
| C073248 | Peptamen |
| D004750 | Enteral Nutrition |
| D000596 | Amino Acids |
| ID | Term |
|---|---|
| D005248 | Feeding Methods |
| D013812 | Therapeutics |
| D018529 | Nutritional Support |
| D044623 | Nutrition Therapy |
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| Prosol 20% IV to 1.75g/kg/day | Dietary Supplement | Patients in group 2 will receive 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/day. |
|
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| Prosol 20% IV to 2.5g/kg/day | Dietary Supplement | 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/d. |
|
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| 0 and 48 hours |
| Biomarker of amino acid restriction or repletion - ELISA (pg/ml) | Blood (one 4-ml tube per sample) will be collected at baseline, then every 12 hours in the first 48 hours, and 72 hours post initiation of amino acid administration. Measures of amino acid-sensitive inflammation include the following: serum C-reactive protein and interleukin-6. | 0, 12, 24, 36, 48, 72 hours |
| Biomarker of amino acid restriction or repletion - mRNA detection (copy number/ml) | Blood (one 2.5-ml tube per sample) will be collected at baseline, then every 12 hours in the first 48 hours, and 72 hours post initiation of amino acid administration. Using Pax-gene tubes, peripheral blood mononuclear cell (PBMC) mRNA will be isolated for detection of interleukin-6 and c-reactive protein gene expression. | 0, 12, 24, 36, 48, 72 hours |
| Biomarker of amino acid restriction or repletion - protein levels (fold increase in Western blot band density) | Blood (one 4 ml cell separator tube per sample) will be collected at baseline, then every 12 hours in the first 48 hours, and 72 hours post initiation of amino acid administration. Measures of amino acid-sensitive cell signaling in peripheral blood mononuclear cells include: phospho- p70 S6 kinase, phospho-S6, or phospho-eiF2α by Western blot. | 0, 12, 24, 36, 48, 72 hours |
| Metabolic Substrates (micromolar) | Plasma amino acids and markers of oxidative stress (glutathione, cysteine, related sulfhydryl) by liquid chromatography tandem mass spectroscopy. Blood will be collected at baseline, then at 24, 48, and 72 hours initiation of amino acid administration. | 0, 24, 36, 48, 72 hours |
| Resting Energy Expenditure (kcal) | Investigators will measure resting energy expenditure by indirect calorimetry at the 5 hour time point of each tracer protocol (Baseline and 48 h after initiation of amino acid administration. This will permit comparison of actual energy expenditure with that estimated by weight-based nomogram used for nutritional dosing. | 0 and 48 hours |
| Ventilator-free days in ICU | Duration of stay in ICU off mechanical ventilation. | 72 hours to 1 year |
| Hospital-acquired infections. | Number of hospital-acquired infections during the hospital admission. | 72 hours to 1 year |
| Mortality | Death in hospital (binary value for dead or alive). | 72 hours to 1 year |
| Derived |
| Omiya K, Sato H, Sato T, Wykes L, Hong M, Hatzakorzian R, Kristof AS, Schricker T. Albumin and fibrinogen kinetics in sepsis: a prospective observational study. Crit Care. 2021 Dec 17;25(1):436. doi: 10.1186/s13054-021-03860-7. |
| D009750 | Nutritional and Metabolic Diseases |
| D000602 |
| Amino Acids, Peptides, and Proteins |