Critical IllnessAA-ICUNCT02865408
Amino Acid Nutrition in the Critically-ill
A study testing Peptamen 1.5% via enteral, Prosol 20% IV to 1.75g/kg/day and Prosol 20% IV to 2.5g/kg/day in people with Critical Illness and Inflammation, run by Arnold Kristof at 1 site in Canada.
Trial summary
Enhancing the anabolic effect of nutrition in critically ill patients by administering exogenous amino acids. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Illness, Inflammation, Malnutrition
- What is being tested?
- Peptamen 1.5% via enteral, Prosol 20% IV to 1.75g/kg/day and Prosol 20% IV to 2.5g/kg/day
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- 1 Mar 2017to 28 Feb 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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- Expected to have life-sustaining treatments withdrawn in the next 3 days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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Enhancing the Anabolic Effect of Nutrition in Critically Ill Patients by Administering Exogenous Amino Acids
Enhancing the anabolic effect of nutrition in critically ill patients by administering exogenous amino acids.
Read the detailed description
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.
- Conditions
- Critical Illness, Inflammation, Malnutrition
- Being tested
- Peptamen 1.5% via enteral, Prosol 20% IV to 1.75g/kg/day, Prosol 20% IV to 2.5g/kg/day
- Keywords
- Amino acids, critically-ill, catabolic, nutrition, anabolic
- Medical subject headings
- Critical Illness, Inflammation, Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Peptamen 1.5% via enteralDietary supplement
Also called Enteral feeding with Peptamen 1.5%
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.
Prosol 20% IV to 1.75g/kg/dayDietary supplement
Also called Enteral feeding with Peptamen 1.5% plus Prosol 20%
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.
Prosol 20% IV to 2.5g/kg/dayDietary supplement
Also called Enteral feeding with Peptamen 1.5% plus Prosol 20%
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Dietary Supplement: Peptamen 1.5% via enteral |
| 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 Receives: Dietary Supplement: Peptamen 1.5% via enteral; Dietary Supplement: Prosol 20% IV to 1.75g/kg/day |
| 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. Receives: Dietary Supplement: Peptamen 1.5% via enteral; Dietary Supplement: Prosol 20% IV to 2.5g/kg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0 and 48 hours
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 0 and 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2016 (estimated)
- Study start1 Mar 2017
- Primary completion28 Jan 2026 (estimated)
- Study completion28 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Arnold Kristof
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Arnold Kristof, McGill University Health Centre/Research Institute of the McGill University Health Centre
- Investigators
- Arnold S Kristof, MDCM, FRCPC, Principal investigator, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02865408
- Sponsor's protocol ID
- 4738
- Acronym
- AA-ICU
- Status last verified
- Sep 2025
- First submitted
- 7 Jul 2015
- Last updated
- 6 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40617772Omiya 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.
PubMed 34920728
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing the Anabolic Effect of Nutrition in Critically Ill Patients by Administering Exogenous Amino Acids
- ClinicalTrials.gov ID
- NCT02865408
- Acronym / sponsor ID
- AA-ICU / 4738
- Conditions
- Critical Illness, Inflammation, Malnutrition
- Keywords
- Amino acids, critically-ill, catabolic, nutrition, anabolic
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Arnold KristofUniversity, hospital or other
- Study start
- 1 Mar 2017 (actual)
- Primary completion
- 28 Jan 2026 (estimated)
- Study completion
- 28 Feb 2026 (estimated)
- First posted
- 12 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Enhancing the anabolic effect of nutrition in critically ill patients by administering exogenous amino acids.
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: Peptamen 1.5% via enteral only | Active comparator | Dietary Supplement: Peptamen 1.5% via enteralStudy 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 |
| Group 2: Prosol 20% IV to 1.75g/kg/day | Active comparator | Dietary Supplement: Peptamen 1.5% via enteral, Dietary Supplement: Prosol 20% IV to 1.75g/kg/dayPatients 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 |
| Group 3: Prosol 20% IV to 2.5g/kg/day | Active comparator | Dietary Supplement: Peptamen 1.5% via enteral, Dietary Supplement: Prosol 20% IV to 2.5g/kg/dayPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Peptamen 1.5% via enteralAlso: Enteral feeding with Peptamen 1.5%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. | Dietary supplement | Group 1: Peptamen 1.5% via enteral only, Group 2: Prosol 20% IV to 1.75g/kg/day, Group 3: Prosol 20% IV to 2.5g/kg/day |
| Prosol 20% IV to 1.75g/kg/dayAlso: Enteral feeding with Peptamen 1.5% plus Prosol 20%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. | Dietary supplement | Group 2: Prosol 20% IV to 1.75g/kg/day |
| Prosol 20% IV to 2.5g/kg/dayAlso: Enteral feeding with Peptamen 1.5% plus Prosol 20%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. | Dietary supplement | Group 3: Prosol 20% IV to 2.5g/kg/day |
Primary outcome
Whole body protein balance
Time frame: 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.
6 secondary outcomes
Synthesis rates of hepatic secretory proteins (the total plasma protein pool, albumin, fibrinogen in %/d)
Time frame: 0 and 48 hours
Biomarker of amino acid restriction or repletion - ELISA (pg/ml)
Time frame: 0, 12, 24, 36, 48, 72 hours
Biomarker of amino acid restriction or repletion - mRNA detection (copy number/ml)
Time frame: 0, 12, 24, 36, 48, 72 hours
Biomarker of amino acid restriction or repletion - protein levels (fold increase in Western blot band density)
Time frame: 0, 12, 24, 36, 48, 72 hours
Metabolic Substrates (micromolar)
Time frame: 0, 24, 36, 48, 72 hours
Resting Energy Expenditure (kcal)
Time frame: 0 and 48 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Derived from this study: PubMed 40617772Kristof 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.
- Derived from this study: PubMed 34920728Omiya 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arnold S Kristof, MDCM, FRCPC principal investigator
McGill University Health Centre/Research Institute of the McGill University Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Peptamen 1.5% via enteral, Prosol 20% IV to 1.75g/kg/day and Prosol 20% IV to 2.5g/kg/day in people with Critical Illness and Inflammation, run by Arnold Kristof at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whole body protein balance (time frame: 0 and 48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02865408, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2025.