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Amino Acid Nutrition in the Critically-ill (AA-ICU)

Primary Purpose

Critical Illness, Inflammation, Malnutrition

Status

Recruiting

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Peptamen 1.5% via enteral

Prosol 20% IV to 1.75g/kg/day

Prosol 20% IV to 2.5g/kg/day

About this trial

This is an interventional prevention trial for Critical Illness focused on measuring Amino acids, critically-ill, catabolic, nutrition, anabolic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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Expected to have life-sustaining treatments withdrawn in the next 3 days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.

Sites / Locations

McGill University health CentreRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

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

Arm Description

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

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT02865408

First Posted

July 7, 2015

Last Updated

April 9, 2022

Sponsor

Arnold Kristof

1. Study Identification

Unique Protocol Identification Number

NCT02865408

Brief Title

Amino Acid Nutrition in the Critically-ill

Acronym

AA-ICU

Official Title

Enhancing the Anabolic Effect of Nutrition in Critically Ill Patients by Administering Exogenous Amino Acids

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

March 1, 2017 (Actual)

Primary Completion Date

February 28, 2023 (Anticipated)

Study Completion Date

February 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Arnold Kristof

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Critical Illness, Inflammation, Malnutrition

Keywords

Amino acids, critically-ill, catabolic, nutrition, anabolic

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group 1: Peptamen 1.5% via enteral only

Arm Type

Active Comparator

Arm Description

Arm Title

Group 2: Prosol 20% IV to 1.75g/kg/day

Arm Type

Active Comparator

Arm Description

Arm Title

Group 3: Prosol 20% IV to 2.5g/kg/day

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

Peptamen 1.5% via enteral

Other Intervention Name(s)

Enteral feeding with Peptamen 1.5%

Intervention Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

Prosol 20% IV to 1.75g/kg/day

Other Intervention Name(s)

Enteral feeding with Peptamen 1.5% plus Prosol 20%

Intervention Description

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.

Intervention Type

Dietary Supplement

Intervention Name(s)

Prosol 20% IV to 2.5g/kg/day

Other Intervention Name(s)

Enteral feeding with Peptamen 1.5% plus Prosol 20%

Intervention Description

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.

Primary Outcome Measure Information:

Title

Whole body protein balance

Description

Time Frame

0 and 48 hours

Secondary Outcome Measure Information:

Title

Synthesis rates of hepatic secretory proteins (the total plasma protein pool, albumin, fibrinogen in %/d)

Description

Time Frame

0 and 48 hours

Title

Biomarker of amino acid restriction or repletion - ELISA (pg/ml)

Description

Time Frame

0, 12, 24, 36, 48, 72 hours

Title

Biomarker of amino acid restriction or repletion - mRNA detection (copy number/ml)

Description

Time Frame

0, 12, 24, 36, 48, 72 hours

Title

Biomarker of amino acid restriction or repletion - protein levels (fold increase in Western blot band density)

Description

Time Frame

0, 12, 24, 36, 48, 72 hours

Title

Metabolic Substrates (micromolar)

Description

Time Frame

0, 24, 36, 48, 72 hours

Title

Resting Energy Expenditure (kcal)

Description

Time Frame

0 and 48 hours

Other Pre-specified Outcome Measures:

Title

ICU length of stay

Description

Duration of ICU admission in days.

Time Frame

72 hours to 1 year

Title

Hospital length of stay

Description

Duration of ICU admission in days.

Time Frame

72 hours to 1 year

Title

Ventilator-free days in ICU

Description

Duration of stay in ICU off mechanical ventilation.

Time Frame

72 hours to 1 year

Title

Hospital-acquired infections.

Description

Number of hospital-acquired infections during the hospital admission.

Time Frame

72 hours to 1 year

Title

Mortality

Description

Death in hospital (binary value for dead or alive).

Time Frame

72 hours to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Arnold S Kristof, MDCM, FRCPC

Phone

501-934-1934

Ext

35251

arnold.kristof@mcgill.ca

First Name & Middle Initial & Last Name or Official Title & Degree

Josie Campisi, RN, CRC

Phone

514-934-1934

Ext

42408

josie.campisi@muhc.mcgill.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arnold S Kristof, MDCM, FRCPC

Organizational Affiliation

McGill University Health Centre/Research Institute of the McGill University Health Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

McGill University health Centre

City

Montréal

State/Province

Quebec

ZIP/Postal Code

H4A 3J1

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Arnold Kristof, MD

Phone

514-934-1934

arnold.kristof@mcgill.ca

First Name & Middle Initial & Last Name & Degree

Josie Campisi, MSc

Phone

514-934-1934

Ext

65542

josie.campisi@muhc.mcgill.ca

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34920728

Citation

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.

Results Reference

derived

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Amino Acid Nutrition in the Critically-ill

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