Intestinal MalabsorptionPANININCT04791774
Protein-bound Versus Free Amino Acid Nutrition During INtestinal Malabsorption in Critical Illness
A study testing Milk protein (food grade protein) and Fee amino acids (food grade amino acids) in people with Intestinal Malabsorption and Critical Illness, run by Maastricht University Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Intestinal Malabsorption, Critical Illness, Protein Malnutrition
- What is being tested?
- Milk protein (food grade protein) and Fee amino acids (food grade amino acids)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- 27 Mar 2018to 30 Nov 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Receiving full enteral nutrition without gastric residual volumes
- Arterial (any location) line in situ
- Flexi-seal system in situ
Who cannot join
- 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.
Show all 18Show fewer
- 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
- Enrolment in any other interventional study
- Milk/lactose allergy
- Previous participation in a 13C amino acid tracer study within the last year
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Systemic Bioavailability of Enteral Protein-bound Versus Free Amino Acid Nutrition During Intestinal Malabsorption in Critical Illness
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.
Read the 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.
- Being tested
- Milk protein (food grade protein), Fee amino acids (food grade amino acids)
- Keywords
- Proteins, Stable Isotopes, Enteral Nutrition
- Medical subject headings
- Malabsorption Syndromes, Critical Illness, Kwashiorkor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Milk protein (food grade protein)Dietary supplement
Also called 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)Dietary supplement
Also called 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
| Study group | Role | What they receive |
|---|---|---|
| Protein group | Active comparator | Patients receive 20 grams of Intrinsically labelled milk protein. Receives: 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 Receives: Dietary Supplement: Fee amino acids (food grade amino acids) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 hours
Secondary outcomes (6)
Total plasma amino acids (AAmax [μmol/L])
Total plasma amino acids (AAmax [μmol/L])
Measured: 8 hours
Plasma glucose (glucosemax [mmol/L])
Plasma glucose (glucosemax [mmol/L])
Measured: 8 hours
Plasma insulin (insulinmax [mU/L])
Plasma insulin (insulinmax [mU/L])
Measured: 8 hours
Intestinal absorption capacity (energy provided - fecal energy loss x 100%)
Intestinal absorption capacity (energy provided - fecal energy loss x 100%)
Measured: 2 x 24 hours
Fecal elastase (µg elastase / g feces)
Fecal elastase (µg elastase / g feces)
Measured: 2 x 24 hours
Fecal presence of L-[1-13C]-phenylalanine
Fecal presence of L-[1-13C]-phenylalanine
Measured: 2x 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2021
- Study start27 Mar 2018
- Primary completion30 Nov 2019
- Study completion30 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Intestinal MalabsorptionStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Maastricht University
- Responsible party
- Sponsor
- Investigators
- Marcel van de Poll, MD, PhD, Principal investigator, Maastricht University Medical Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04791774
- Sponsor's protocol ID
- NL60452.068.17
- Acronym
- PANINI
- Status last verified
- Mar 2021
- First submitted
- 2 May 2017
- Last updated
- 10 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38103646
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Systemic Bioavailability of Enteral Protein-bound Versus Free Amino Acid Nutrition During Intestinal Malabsorption in Critical Illness
- ClinicalTrials.gov ID
- NCT04791774
- Acronym / sponsor ID
- PANINI / NL60452.068.17
- Keywords
- Proteins, Stable Isotopes, Enteral Nutrition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Maastricht University
- Study start
- 27 Mar 2018 (actual)
- Primary completion
- 30 Nov 2019 (actual)
- Study completion
- 30 Nov 2019 (actual)
- First posted
- 10 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Protein group | Active comparator | Dietary Supplement: Milk protein (food grade protein)Patients receive 20 grams of Intrinsically labelled milk protein. |
| Free amino acid group | Experimental | Dietary Supplement: Fee amino acids (food grade amino acids)Patients receive 20 grams of free amino acids equivalent to the milk protein labelled with 13C-Phenylalanine |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Milk protein (food grade protein)Also: ProteinSubjects will receive an enteral nutritional formula containing 20 grams intrinsically labeled (1-[13C]-phenylalanine) milk protein | Dietary supplement | Protein group |
| Fee amino acids (food grade amino acids)Also: Amino AcidsNutritional formula containing 20 grams of a free amino acid mixture equivalent in composition to the milk protein with 1-[13C]-labeled phenylalanine | Dietary supplement | Free amino acid group |
Primary outcome
systemic availability of diet-derived amino acids
Time frame: 8 hours
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.
6 secondary outcomes
Total plasma amino acids (AAmax [μmol/L])
Time frame: 8 hours
Plasma glucose (glucosemax [mmol/L])
Time frame: 8 hours
Plasma insulin (insulinmax [mU/L])
Time frame: 8 hours
Intestinal absorption capacity (energy provided - fecal energy loss x 100%)
Time frame: 2 x 24 hours
Fecal elastase (µg elastase / g feces)
Time frame: 2 x 24 hours
Fecal presence of L-[1-13C]-phenylalanine
Time frame: 2x 12 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2021.
- Derived from this study: PubMed 38103646van 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.
- Individual participant dataSharing planned: No
Related trials for Intestinal Malabsorption
RecruitingPhase 3
Efficacy And Safety Evaluation of Glepaglutide in Treatment of SBS
Short Bowel Syndrome
Enrolling by invitation
Immune Responses to Gluten
Celiac Disease, Malabsorption Syndromes
Active, not recruitingPhase 3
Efficacy and Safety Evaluation of Glepaglutide in Treatment of Short Bowel Syndrome
Short Bowel Syndrome (SBS)
RecruitingPhase 2
Assess the Safety of ELGN-2112 in Preterm Infants Born Under 26 Weeks GA and IUGR Infants Born 26-32 Weeks GA
Intestinal Malabsorption
Not yet recruitingObservational study
Long-term Health Outcomes of Screen Detected and Potential Celiac Disease Patients
Malabsorption Syndromes, Intestinal Diseases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcel van de Poll, MD, PhD principal investigator
Maastricht University Medical Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Milk protein (food grade protein) and Fee amino acids (food grade amino acids) in people with Intestinal Malabsorption and Critical Illness, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
systemic availability of diet-derived amino acids (time frame: 8 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04791774, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2021; AzTrials last refreshed its copy on 7 Nov 2026.