Protein-bound Versus Free Amino Acid Nutrition During INtestinal Malabsorption in Critical Illness

NCT04791774 | Completed

• 1 other identifier: NL60452.068.17
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

In the current study, we willquantitate the difference in digestion and absorption kinetics of dietary whole protein versus free amino acids in vivo in critically ill patients admitted to the intensive care unit suffering from malabsorption. 16 adult, mechanically ventilated ICU patients with clinical signs of malabsorption (faecal weight \>350 g/day) will be included. All patients will receive a primed continuous intravenous infusion of L-\[ring2H5\]-phenylalanine and L-\[3,5-2H2\]-Tyrosine for the duration of the study period. After reaching an isotopic steady state (1.5 hours), patients will receive either \[1-13C\]- phenylalanine labelled milk protein or free amino acids with an identical constitution and \[1-13C\]-phenylalanine. Main study endpoint will be the splanchnic extraction of phenylalanine, calculated from systemic \[1-13C\]- and L-\[ring2H5\]-phenylalanine enrichment.

Conditions

Intestinal Malabsorption; Critical Illness; Protein Malnutrition

Keywords

Proteins; Stable Isotopes; Enteral Nutrition

Outcome Measures

Primary Outcomes (1)

• systemic availability of diet-derived amino acids

  The main study endpoint in this study is the systemic availability of enteral administered protein-bound or free amino acid nutrition, including the rate of appearance (Ra) of dietary derived phenylalanine. Modified Steele's equations will be applied to plasma enrichments of L-\[ring-2H5\]-phenylalanine, L-\[1-13C\]-phenylalanine enrichment, L-\[ring-2H4\]-tyrosine and L-\[3,5-2H2\]-tyrosine.

  8 hours

Secondary Outcomes (6)

• Total plasma amino acids (AAmax [μmol/L])

  8 hours

• Plasma glucose (glucosemax [mmol/L])

  8 hours

• Plasma insulin (insulinmax [mU/L])

  8 hours

• Intestinal absorption capacity (energy provided - fecal energy loss x 100%)

  2 x 24 hours

• Fecal elastase (µg elastase / g feces)

  2 x 24 hours

Study Arms (2)

Protein group

ACTIVE COMPARATOR

Patients receive 20 grams of Intrinsically labelled milk protein.

Dietary Supplement: Milk protein (food grade protein)

Free amino acid group

EXPERIMENTAL

Patients receive 20 grams of free amino acids equivalent to the milk protein labelled with 13C-Phenylalanine

Dietary Supplement: Fee amino acids (food grade amino acids)

Interventions

Milk protein (food grade protein) DIETARY_SUPPLEMENT

Subjects will receive an enteral nutritional formula containing 20 grams intrinsically labeled (1-\[13C\]-phenylalanine) milk protein

Also known as: Protein

Protein group

Fee amino acids (food grade amino acids) DIETARY_SUPPLEMENT

Nutritional formula containing 20 grams of a free amino acid mixture equivalent in composition to the milk protein with 1-\[13C\]-labeled phenylalanine

Also known as: Amino Acids

Free amino acid group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 and \< 75 years
• Fecal weight \> 350g/day
• Critical illness of any origin (e.g. medical, surgical, trauma) requiring admittance on ICU ward.
• Expected ICU stay for the duration of the study protocol
• Mechanically ventilated (PaO2/FiO2 ratio of \>100 and \<300)
• Nasogastric tube in situ
• Receiving full enteral nutrition without gastric residual volumes
• Arterial (any location) line in situ
• Flexi-seal system in situ

You may not qualify if:

• Proven (pre-existing) intestinal disease that potentially limits normal gut function and absorption of nutrients (e.g. IBD, short-bowel, entero-cutaneous fistulas including a surgical enterostomy)
• Proven (pre-existing) primary pancreatic disease or obstruction of the pancreatic duct of any origin (e.g. pancreatitis, carcinoma).
• Patients who are moribund (not expected to be in ICU for more than 48 hours due to imminent death)
• A lack of commitment to full aggressive care during the first week due to severity of illness, comorbidities and potential harm from maximal treatment (anticipated withholding or withdrawing treatments)
• Absolute contraindication to enteral nutrients (e.g., gastrointestinal \[GI\] perforation, obstruction or no GI tract access for any reason)
• Receiving parenteral nutrition.
• Nasoduodenal or nasojejunal feeding tube
• Renal dysfunction defined as a serum creatinine \>171 umol/L or a urine output of less than 500 ml/last 24 hours
• Patients requiring chronic veno-venous hemofiltration
• Patients on ECMO/ELS
• Cirrhosis - Child Pugh class C/D liver disease
• Patients with primary admission diagnosis of burns (\>30% body surface area)
• Weight less than 50 kg or greater than 100 kg
• Pregnant patients or lactating with the intent to breastfeed
• Previous randomization in this study

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Maastricht University: collaborator

Study Sites (1)

Maastricht UMC+

Maastricht, 6229HX, Netherlands

Location

Related Publications (1)

• van Gassel RJ, Weijzen ME, Kouw IW, Senden JM, Wodzig WK, Olde Damink SW, van de Poll MC, van Loon LJ. Administration of Free Amino Acids Improves Exogenous Amino Acid Availability when Compared with Intact Protein in Critically Ill Patients: A Randomized Controlled Study. J Nutr. 2024 Feb;154(2):554-564. doi: 10.1016/j.tjnut.2023.12.015. Epub 2023 Dec 15.

  PMID: 38103646 DERIVED

MeSH Terms

Conditions

Malabsorption Syndromes; Critical Illness; Kwashiorkor

Interventions

Milk Proteins; Proteins; Amino Acids

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Severe Acute Malnutrition; Malnutrition; Nutrition Disorders

Intervention Hierarchy (Ancestors)

Animal Proteins, Dietary; Dietary Proteins; Amino Acids, Peptides, and Proteins; Food; Diet, Food, and Nutrition; Physiological Phenomena; Milk; Dairy Products; Food and Beverages

Study Officials

• Marcel van de Poll, MD, PhD

  Maastricht University Medical Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: March 10, 2021
• Study Start: March 27, 2018
• Primary Completion: November 30, 2019
• Study Completion: November 30, 2019
• Last Updated: March 10, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)