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

Critical Illness Clinical Trial

— PANINI  

Official title:

Systemic Bioavailability of Enteral Protein-bound Versus Free Amino Acid Nutrition During Intestinal Malabsorption in Critical Illness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04791774
• Other study ID #: NL60452.068.17
• Status: Completed
• Phase: N/A
• Start date: March 27, 2018
• Est. completion date: November 30, 2019

Study information

• Verified date: March 2021
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 30, 2019
• Est. primary completion date: November 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age > 18 and < 75 years

2. Fecal weight > 350g/day

3. Critical illness of any origin (e.g. medical, surgical, trauma) requiring admittance on ICU ward.

4. Expected ICU stay for the duration of the study protocol

5. Mechanically ventilated (PaO2/FiO2 ratio of >100 and <300)

6. Nasogastric tube in situ

7. Receiving full enteral nutrition without gastric residual volumes

8. Arterial (any location) line in situ

9. Flexi-seal system in situ

Exclusion Criteria:

1. 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)

2. Proven (pre-existing) primary pancreatic disease or obstruction of the pancreatic duct of any origin (e.g. pancreatitis, carcinoma).

3. Patients who are moribund (not expected to be in ICU for more than 48 hours due to imminent death)

4. 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)

5. Absolute contraindication to enteral nutrients (e.g., gastrointestinal [GI] perforation, obstruction or no GI tract access for any reason)

6. Receiving parenteral nutrition.

7. Nasoduodenal or nasojejunal feeding tube

8. Renal dysfunction defined as a serum creatinine >171 umol/L or a urine output of less than 500 ml/last 24 hours

9. Patients requiring chronic veno-venous hemofiltration

10. Patients on ECMO/ELS

11. Cirrhosis - Child Pugh class C/D liver disease

12. Patients with primary admission diagnosis of burns (>30% body surface area)

13. Weight less than 50 kg or greater than 100 kg

14. Pregnant patients or lactating with the intent to breastfeed

15. Previous randomization in this study

16. Enrolment in any other interventional study

17. Milk/lactose allergy

18. Previous participation in a 13C amino acid tracer study within the last year

Related Conditions & MeSH terms

• Critical Illness
• Intestinal Malabsorption
• Kwashiorkor
• Malabsorption Syndromes
• Malnutrition
• Protein Malnutrition

Intervention

Dietary Supplement:
• Milk protein (food grade protein)
Subjects will receive an enteral nutritional formula containing 20 grams intrinsically labeled (1-[13C]-phenylalanine) milk protein
• Fee amino acids (food grade amino acids)
Nutritional formula containing 20 grams of a free amino acid mixture equivalent in composition to the milk protein with 1-[13C]-labeled phenylalanine

Locations

Country	Name	City	State
Netherlands	Maastricht UMC+	Maastricht

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Maastricht University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Total plasma amino acids (AAmax [µmol/L])	Total plasma amino acids (AAmax [µmol/L])	8 hours
Secondary	Plasma glucose (glucosemax [mmol/L])	Plasma glucose (glucosemax [mmol/L])	8 hours
Secondary	Plasma insulin (insulinmax [mU/L])	Plasma insulin (insulinmax [mU/L])	8 hours
Secondary	Intestinal absorption capacity (energy provided - fecal energy loss x 100%)	Intestinal absorption capacity (energy provided - fecal energy loss x 100%)	2 x 24 hours
Secondary	Fecal elastase (µg elastase / g feces)	Fecal elastase (µg elastase / g feces)	2 x 24 hours
Secondary	Fecal presence of L-[1-13C]-phenylalanine	Fecal presence of L-[1-13C]-phenylalanine	2x 12 hours