Protein-bound Versus Free Amino Acid Nutrition During INtestinal Malabsorption in Critical Illness
Condition: Intestinal Malabsorption; Critical Illness; Protein Malnutrition
MeSH terms: Malabsorption Syndromes; Malnutrition; Kwashiorkor; Critical Illness
Study type: Interventional

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.
    

Detailed description: 
      Background of the study:

      The importance of the provision of sufficient protein in critical illness is increasingly
      recognized. Protein malabsorption seems to be an underestimated but substantial problem in
      critically ill patients, limiting the amount of this important nutrient that actually becomes
      available within the systemic circulation. Among several contributors to malabsorption in
      critical illness, exocrine pancreatic insufficiency has recently emerged as a regularly
      occurring phenomenon during critical illness. Pancreatic insufficiency could lead to reduced
      digestion and subsequent uptake of enteral provided proteins. A proposed solution to this
      problem could be the use of elementary feeds containing free amino acids instead of whole
      protein. Due to the lack of easy applicable and reproducible tests for protein malabsorption
      the true efficacy of these feeds is still unknown. We hypothesize that enteral nutrition
      containing free amino acids leads to higher systemic levels of amino acids and will therefore
      increase the amount of dietary amino acids available for protein synthesis.

      Objective of the study:

      To quantitate the difference in digestion and absorption kinetics of dietary whole protein
      versus free amino acids in vivo in patients admitted to the ICU suffering from malabsorption.

      Study design:

      Randomized, single-blind controlled, single-centre, intervention study.

      Study population:

      16 adult, mechanically ventilated ICU patients with clinical signs of malabsorption (faecal
      weight >350 g/day).

      Intervention:

      Normal enteral nutrition will be ceased 8 hours before the start of study participation. 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.

      Primary study parameters/outcome of the study:

      Main study endpoint will be the splanchnic extraction of phenylalanine, calculated from
      systemic [1-13C]- and L-[ring2H5]-phenylalanine enrichment.

      Secundary study parameters/outcome of the study:

      Secondary endpoints include the impact of enteral nutrition on whole body protein balance,
      glucose and insulin concentrations and faecal energy and protein loss as a measure of
      malabsorption.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness:

      Total study participation will take 16 hours, including 8 hours of fasting. Arterial blood
      samples will be collected regularly, with 50 ml of blood being sampled in total, amounting to
      a maximum of 1.0% of total circulating volume. All infusions, as well as blood sample
      collection, will be performed through indwelling catheters necessary for normal ICU
      treatment, meaning no lines or nasogastric tubes will have to be placed for the purposes of
      the study. Both isotopically labelled protein and free amino acids have been proven safe for
      use in humans and carry no harmful risks for the study participant. Changes in protein
      digestion, absorption and metabolism are specific to critical illness and their impact on the
      clinical condition and recovery of patients is severe. Investigating new strategies to
      modulate these effects are therefore essential, but require experimental studies in a
      vulnerable population. The risks in the present study are minimal whereas the results could
      help improve nutritional management in the intensive care.
    

Intervention name(s): Milk protein (food grade protein); Fee amino acids (food grade amino acids)
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Subjects will receive an enteral nutritional formula containing 20 grams intrinsically labeled (1-[13C]-phenylalanine) milk protein; Nutritional formula containing 20 grams of a free amino acid mixture equivalent in composition to the milk protein with 1-[13C]-labeled phenylalanine
Other intervention name(s): Protein; Amino Acids
Intervention MeSH terms: Caseins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Basic Science
Keywords: Proteins; Stable Isotopes; Enteral Nutrition