- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02865408
Amino Acid Nutrition in the Critically-ill (AA-ICU)
March 9, 2024 updated by: Arnold Kristof
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.
Study Overview
Status
Recruiting
Conditions
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 Type
Interventional
Enrollment (Estimated)
30
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Arnold S Kristof, MDCM, FRCPC
- Phone Number: 35251 501-934-1934
- Email: arnold.kristof@mcgill.ca
Study Contact Backup
- Name: Josie Campisi, RN, CRC
- Phone Number: 42408 514-934-1934
- Email: josie.campisi@muhc.mcgill.ca
Study Locations
-
-
Quebec
-
Montréal, Quebec, Canada, H4A 3J1
- Recruiting
- McGill University Health Centre
-
Contact:
- Arnold Kristof, MD
- Phone Number: 514-934-1934
- Email: arnold.kristof@mcgill.ca
-
Contact:
- Josie Campisi, MSc
- Phone Number: 65542 514-934-1934
- Email: josie.campisi@muhc.mcgill.ca
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 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
|
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.
Other Names:
|
Active Comparator: 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
|
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.
Other Names:
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.
Other Names:
|
Active Comparator: 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.
|
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.
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
0 and 48 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Synthesis rates of hepatic secretory proteins (the total plasma protein pool, albumin, fibrinogen in %/d)
Time Frame: 0 and 48 hours
|
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.
|
0 and 48 hours
|
Biomarker of amino acid restriction or repletion - ELISA (pg/ml)
Time Frame: 0, 12, 24, 36, 48, 72 hours
|
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)
Time Frame: 0, 12, 24, 36, 48, 72 hours
|
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)
Time Frame: 0, 12, 24, 36, 48, 72 hours
|
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)
Time Frame: 0, 24, 36, 48, 72 hours
|
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)
Time Frame: 0 and 48 hours
|
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
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ICU length of stay
Time Frame: 72 hours to 1 year
|
Duration of ICU admission in days.
|
72 hours to 1 year
|
Hospital length of stay
Time Frame: 72 hours to 1 year
|
Duration of ICU admission in days.
|
72 hours to 1 year
|
Ventilator-free days in ICU
Time Frame: 72 hours to 1 year
|
Duration of stay in ICU off mechanical ventilation.
|
72 hours to 1 year
|
Hospital-acquired infections.
Time Frame: 72 hours to 1 year
|
Number of hospital-acquired infections during the hospital admission.
|
72 hours to 1 year
|
Mortality
Time Frame: 72 hours to 1 year
|
Death in hospital (binary value for dead or alive).
|
72 hours to 1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Arnold S Kristof, MDCM, FRCPC, McGill University Health Centre/Research Institute of the McGill University Health Centre
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 1, 2017
Primary Completion (Estimated)
June 28, 2024
Study Completion (Estimated)
February 28, 2025
Study Registration Dates
First Submitted
July 7, 2015
First Submitted That Met QC Criteria
August 9, 2016
First Posted (Estimated)
August 12, 2016
Study Record Updates
Last Update Posted (Actual)
March 12, 2024
Last Update Submitted That Met QC Criteria
March 9, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 4738
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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