Indicator Amino Acid Oxidation in ICU Patients (IAAO-IC)

The Effect of Standard or Higher Protein Feeding on Indicator Amino Acid Oxidation in ICU Patients

This study will use the indicator amino acid oxidation technique (IAAO) to determine protein oxidation of ICU patients at two protein intakes: 1.3 g/kg/d versus 2.0 g/kg/d.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Muscle Wasting
• Intervention / Treatment: Combination product: Standard protein enteral nutrition with enteral tracer; Combination product: High protein enteral nutrition with enteral tracer

Detailed Description

Rationale:

While protein administration guidelines for critical care are available from international organizations such as ASPEN and ESPEN, they vary greatly in their recommended dose and are based on relatively low-quality evidence. The Indicator Amino Acid Oxidation (IAAO) technique has been developed as a more practical and non-invasive tool to assess protein metabolism that can be used in vulnerable populations. Application of the IAAO technique in patients admitted to the Intensive Care Unit (ICU) could provide an alternative to better investigate optimal protein feeding during critical illness.

Objective:

To assess the effect of enteral feeding with higher protein content compared to standard protein content on indicator amino acid oxidation in ICU patients.

Study design:

Randomized, counterbalanced, cross-over trial.

Study population:

Adult patients with an unplanned admission to the ICU, who are mechanically ventilated and have an indication for prolonged enteral nutrition.

Intervention:

Subjects will undergo two test days in randomized order during which they receive either enteral feeding according to a standard protein dose (1.3 g/kg/d) or a higher protein dose (2.0 g/kg/d). Continuous feeding of L-[1-13C]-phenylalanine combined with breath, urine and blood samples will be applied to assess indicator amino acid oxidation.

Main study parameters/endpoints:

The primary endpoint is indicator amino acid oxidation after enteral feeding with a standard or higher protein content, determined using the Indicator Amino Acid Oxidation (IAAO) method by measuring 13CO2 enrichment in expired breath and enrichment of L-[1-13C]-phenylalanine in plasma and urine.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The overall risk of the study is negligible. The current study compares the effect of two nutritional compositions, that fall within the recommendations of international guidelines on ICU nutrition, on protein metabolism following ICU admission. To avoid overfeeding in the early phase of critical illness, both in terms of calories and protein, full enteral nutrition is provided after three days of gradual increase of intake (i.e., 25-50-75% of targeted intake, on days 1-2-3 respectively). Sampling of breath, urine, feces and plasma does not bring additional risks for this population. Our department has an extensive background in amino acid stable isotope methodology, assessment of 13CO2 enrichment in expired breath samples, and assessment of carbon dioxide production by indirect calorimetry.

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julia Bels, M.D.; Phone Number: +316 30 48 06 85; Email: julia.bels@mumc.nl
• Study Contact Backup: Name: Jorn Trommelen, Ph.D.; Email: jorn.trommelen@maastrichtuniversity.nl

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Recruiting
      • Maastricht University Medical Center+
      • Contact: Julia Bels, M.D.; Phone Number: +31630480685

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 18 years old
• Unplanned admission to the ICU
• Mechanically ventilated
• Start of enteral nutrition within 2 days of intubation
• ≥ 3 days on enteral nutrition
• Expected remaining ICU stay on mechanical ventilation of ≥ 2 days

Exclusion Criteria:

• Contra-indication for enteral nutrition at the discretion of the treating physician
• Feeding intolerance during incremental feeding protocol
• Moribund or withholding of treatment
• On extracorporeal membrane oxygenation (ECMO)
• Presence of chest drains, pneumothorax, tracheoesophageal fistula or subcutaneous emphysema
• Kidney failure AND a "no dialysis"-code on admission
• Hepatic encephalopathy (West Haven criteria 3-4)
• BMI < 18 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1.3 g/kg/day followed by 2.0 g/kg/day; Patients in this arm will, on their first test day, receive enteral nutrition containing 1.3 grams of protein per kg of body weight per day followed by 2.0 grams of protein per kg of body weight per day on their second test day.	Combination product: Standard protein enteral nutrition with enteral tracer; Enteral nutrition with standard (1.3 g/kg/d) protein provision, given via a nasogastric tube. An oral L-[1-13C]-phenylalanine tracer is given as co-intervention. Use of an enterally given tracer is necessary to determine indicator amino acid oxidation.; Combination product: High protein enteral nutrition with enteral tracer; Enteral nutrition with high (2.0 g/kg/d) protein provision, given via a nasogastric tube. An oral L-[1-13C]-phenylalanine tracer is given as co-intervention. Use of an enterally given tracer is necessary to determine indicator amino acid oxidation.
Other: 2.0 g/kg/day followed by 1.3 g/kg/day; Patients in this arm will, on their first test day, receive enteral nutrition containing 2.0 grams of protein per kg of body weight per day followed by 1.3 grams of protein per kg of body weight per day on their second test day.	Combination product: Standard protein enteral nutrition with enteral tracer; Enteral nutrition with standard (1.3 g/kg/d) protein provision, given via a nasogastric tube. An oral L-[1-13C]-phenylalanine tracer is given as co-intervention. Use of an enterally given tracer is necessary to determine indicator amino acid oxidation.; Combination product: High protein enteral nutrition with enteral tracer; Enteral nutrition with high (2.0 g/kg/d) protein provision, given via a nasogastric tube. An oral L-[1-13C]-phenylalanine tracer is given as co-intervention. Use of an enterally given tracer is necessary to determine indicator amino acid oxidation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indicator amino acid oxidation	Indicator amino acid oxidation expressed as µmol/kg/h	Collected at standard vs higher protein administration, on test day 1 and 2 (depending on randomisation order), during the first week of ICU admission.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
13CO2 excretion in breath (F13CO2)	Collected using breath samples; measured using gas chromatography-mass spectrometry (Agilent G1530N/G2589A, Little Falls, USA)	Collected at standard vs higher protein administration, on test day 1 and 2 (depending on randomisation order), during the first week of ICU admission. Per test day: collected before start of tracer and at end of tracer protocol.
Concentration of plasma phenylalanine	Collected via in situ arterial catheter; analyzed using high performance liquid chromatography	Collected at standard vs higher protein administration, on test day 1 and 2 (depending on randomisation order), during the first week of ICU admission. Per test day: collected before start of tracer and at end of tracer protocol.
Fecal output and fecal protein content	Collected via in situ fecal collection bag; protein content in fecal samples will be measured using Dumas method (Variomax CN-analyser)	Collected at standard vs higher protein administration, on test day 1 and 2 (depending on randomisation order), during the first week of ICU admission. Per test day: collected from start of intervention until end of intervention & tracer protocol.
Enrichment of breath 13CO2	Collected using breath samples; measured using gas chromatography-mass spectrometry (Agilent G1530N/G2589A, Little Falls, USA)	Collected at standard vs higher protein administration, on test day 1 and 2 (depending on randomisation order), during the first week of ICU admission. Per test day: collected before start of tracer and at end of tracer protocol.
CO2 production	Measured using indirect calorimetry	Collected at standard vs higher protein administration, on test day 1 and 2 (depending on randomisation order), during the first week of ICU admission. Per test day: collected 2 hours after start of tracer protocol.
Enrichments of plasma L-[1-13C]-phenylalanine	Collected via in situ arterial catheter; measured using gas chromatography-mass spectrometry (Agilent G1530N/G2589A, Little Falls, USA)	Collected at standard vs higher protein administration, on test day 1 and 2 (depending on randomisation order), during the first week of ICU admission. Per test day: collected before start of tracer and at end of tracer protocol.
Enrichments of urine L-[1-13C]-phenylalanine	Collected via indwelling urinary catheter; measured using gas chromatography-mass spectrometry (Agilent G1530N/G2589A, Little Falls, USA)	Collected at standard vs higher protein administration, on test day 1 and 2 (depending on randomisation order), during the first week of ICU admission. Per test day: collected before start of tracer and at end of tracer protocol.

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Maastricht University Medical Center
• Investigators: Principal Investigator: Luc van Loon, Ph.D., Maastricht University

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: October 18, 2023
• First Submitted That Met QC Criteria: October 26, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Enteral Nutrition; Dietary Protein
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Disease Attributes; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Muscular Atrophy; Critical Illness
• Other Study ID Numbers: NL84098.000.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study data can be made available upon reasonable request, which will be considered by the project investigators (Drs. Julia Bels, Dr. Jorn Trommelen) and the Principal Investigator (Prof. Dr. Luc van Loon). A request for data-sharing together with a developed study protocol are prerequisites for consideration.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No