Protein MalabsorptionGutFeedingNCT06091852
The Incorporation of Dietary Protein-Derived Amino Acids in Duodenal Epithelium
A study testing Intrinsically labelled milk protein in people with Protein Malabsorption, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion.This anabolic resistance may be related to decreased postprandial amino acid release in the circulation, due to greater amino acid extraction by splanchnic tissues in older individuals. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Protein Malabsorption
- What is being tested?
- Intrinsically labelled milk protein
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- 24 Jul 2023to 5 Apr 2024
- 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 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male sex
- Aged 18-35 years or 67+ years
- Body mass index (BMI) between 18.5 and 30 kg/m2
Who cannot join
- History of cardiovascular, respiratory, gastrointestinal, urogenital, neurological, psychiatric, dermatologic, musculoskeletal, metabolic, endocrine, haematological, immunologic disorders, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol, interfere with the execution of the experiment, or potential influence the study outcomes (to be decided by the principal investigator and responsible physician)
- Major abdominal surgery interfering with gastrointestinal function (upon judgement of the principal investigator and responsible physician)
- Use of medication which limit participation in or completion of the study protocol, interferes with the execution of the experiment, or potential influences the study outcomes (to be decided by the principal investigator and responsible physician)
- Use of supplementation (i.e. vitamin, pre- and probiotic supplementation) within 14 days prior to testing
- Administration of investigational drugs or participation in any scientific intervention study in the 14 days prior to the study, which may interfere with this study (upon judgement of the principal investigator and responsible physician)
- Specific diet (e.g. vegetarian, vegan, gluten free, no diary) within the study period
Show all 14Show fewer
- Planning to lose weight during the study period
- Lactose intolerance
- Excessive alcohol consumption (defined as > 14 alcoholic consumptions per week)
- Smoking
- Drug use
- Donated blood two months prior to the test day
- Recent (<1 year) participation in amino acid tracer (L-[ring-2H5]-phenylalanine, L-[ring-2H3]-leucine, L-[ring-2H4]-lysine, L-[ring-2H2]-tyrosine) or intrinsically labelled protein ([1-13C]-phenylalanine, [1-13C]-leucine, [1-13C]-lysine) studies
- No given permission to register participation in electronic patient file at MUMC+ and to add records of gastroduodenoscopy
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Maastricht University Medical Center+
Maastricht, 6229ER
About this study
Official title: The Incorporation of Dietary Protein-Derived Amino Acids in Duodenal Mucosal Protein in Young and Older Males
Rationale: Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion.This anabolic resistance may be related to decreased postprandial amino acid release in the circulation, due to greater amino acid extraction by splanchnic tissues in older individuals. It has been suggested that extracted amino acids are utilized by intestinal epithelial cells for cell proliferation, generating new cells to maintain healthy mucosa. So far, there is no evidence that dietary protein-derived amino acids are taken up and incorporated in intestinal mucosal protein in vivo in humans. Furthermore, there is no evidence that this process is impacted by age.
Objective: To assess the postprandial incorporation of dietary protein-derived amino acids in intestinal mucosal protein in healthy young and older males.
Read more
Study design: Cross-sectional, non-therapeutic intervention study design
Study population: 5 healthy, non-obese (BMI 18.5-30kg/m2) young adult males (age: 18-35y inclusive) and 5 community dwelling older males (age: 67+y).
Intervention: Continuous intravenous stable isotope amino acid tracer infusion will be applied, in combination with oral ingestion of 20g intrinsically labelled milk protein, with plasma, muscle and duodenal mucosa biopsy samples collected at different time points throughout the experimental test day.
Main study parameters/endpoints: The primary study outcome is the postprandial (0-5h) incorporation of dietary protein-derived amino acids in duodenal mucosal protein following the ingestion of 20g intrinsically labelled milk protein. Secondary study parameters include postprandial plasma availability of dietary protein-derived amino acids and fractional duodenal mucosal protein synthetic rate.
Read the detailed description
Skeletal muscle tissue is in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates, with a turnover rate of 1-2% per day. It has been well established that protein ingestion is a major anabolic stimulus for muscle protein synthesis. Dietary protein ingestion provides amino acids that stimulate protein synthesis by both functioning as substrate and as signalling molecules that upregulate anabolic pathways.
The anabolic properties of dietary protein largely depend on the protein digestion and amino acid absorption kinetics and subsequent increase in plasma amino acid availability. Following protein ingestion, protein is cleaved into small peptides and amino acids by digestive enzymes. Subsequently, these amino acids are absorbed across the intestinal mucosa by various membrane-bound transporters. The majority of dietary protein derived amino acids is released into the systemic circulation and transported and taken up by various peripheral tissues in the postprandial phase. However, a substantial part of the ingested protein does not become available in the circulation. This part is either not (yet) digested and absorbed, or the absorbed amino acids are taken up by splanchnic tissues, such as the gut and liver, providing precursors for de novo tissue protein synthesis, termed first-pass splanchnic extraction. Previous work in our laboratory has estimated that up to 40% of the protein derived amino acids are taken up and incorporated in the intestinal tract and liver tissues. The intestine is the most highly regenerative organ in the human body, regenerating its epithelium every 3 to 5 days. It has been suggested that the absorbed amino acids are utilized by epithelial cells for rapid cell proliferation, generating new cells to maintain healthy mucosa. Human studies on the incorporation of dietary protein-derived amino acids in intestinal mucosal protein have not been performed. Therefore, the aim of the present explorative in vivo study is to assess, for the first time, the incorporation of dietary protein-derived amino acids in duodenal mucosal protein in humans, and the systemic availability of dietary protein-derived amino acids.
Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion. This proposed anabolic resistance may be related to a decreased postprandial amino acid release in the circulation, due to impairments in protein digestion and amino acid absorption, and greater first-pass splanchnic amino acid extraction in older individuals. Whether dietary protein-derived amino acid incorporation in intestinal mucosal protein is increased with aging remains to be established. Therefore, the current study will use the data on incorporation of dietary protein-derived amino acids in duodenal mucosal protein and postprandial amino acid plasma availability obtained in young and older individuals to evaluate potential age-related differences.
Two primary hypotheses will be tested:
- It is hypothesized that part of the absorbed amino acids will be directly incorporated in duodenal epithelium within 5 hours after protein ingestion.
- It is hypothesized that the extent of postprandial incorporation of dietary protein derived amino acids in duodenal epithelium will be greater in older compared to young males.
- Conditions
- Protein Malabsorption
- Being tested
- Intrinsically labelled milk protein
- Keywords
- Gastrointestinal tract, Intestinal mucosa, Protein, Digestion, Absorption, Aging, Muscle protein synthesis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrinsically labelled milk proteinDietary supplement
20 grams of protein dissolved in 500 mL of water
| Study group | Role | What they receive |
|---|---|---|
| Intrinsically labelled milk protein | Experimental | 20 grams of protein dissolved in 500 mL of water Receives: Dietary Supplement: Intrinsically labelled milk protein |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein
Assessed by duodenal mucosal protein-bound [1-13C]-phenylalanine enrichment (expressed as MPE)
Measured: 0-5 hours
Impact of age on postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein
Assessed by duodenal mucosal protein-bound [1-13C]-phenylalanine enrichment (expressed as MPE) in young and older adults
Measured: 0-5 hours
Secondary outcomes (8)
Postprandial plasma amino acid concentrations
Appearance of milk protein-derived amino acids in plasma over the full assessment period (5 h), as determined using stable isotope tracer methodology
Measured: 0-5 hours
Fractional duodenal mucosal protein synthetic rate
Mucosal protein synthesis rates are calculated using L-ring-2H5-phenylalanine tracer and provided as 1 integrated value over the specified timeframe using plasma as precursor
Measured: 0-5 hours
Fractional muscle protein synthetic rate
Muscle protein synthesis rates are calculated using L-ring-2H5-phenylalanine tracer and provided as 1 integrated value over the specified timeframe using plasma as precursor
Measured: 0-5 hours
Fecal [1-13C]-phenylalanine enrichments (expressed as MPE)
Fecal protein excretion, assessed by fecal [1-13C]-phenylalanine enrichments (expressed as MPE)
Measured: Fecal sample of first feces after endoscopy
Fecal nitrogen content
Fecal protein excretion, assessed by fecal nitrogen content
Measured: Fecal sample of first feces after endoscopy
Fecal microbial metabolites
Microbial metabolites, including short-chain fatty acids, assessed by analyzing fecal samples
Measured: Fecal sample of first feces after endoscopy
Plasma glucose concentrations
Plasma glucose concentrations
Measured: 0-5 hours
Plasma insulin concentrations
Plasma insulin concentrations
Measured: 0-5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2023
- Study start24 Jul 2023
- Primary completion5 Apr 2024
- Study completion5 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Protein 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
- Not applicable
- Intervention model
- Single group
- Model description
- Young vs. old
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- FrieslandCampina
- Responsible party
- Sponsor
- Investigators
- Luc van Loon, Prof, Principal investigator, Maastricht University Medical CenterDaisy Jonkers, Prof, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06091852
- Sponsor's protocol ID
- METC23-011
- Acronym
- GutFeeding
- Status last verified
- Oct 2023
- First submitted
- 27 Jun 2023
- Last updated
- 30 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Incorporation of Dietary Protein-Derived Amino Acids in Duodenal Mucosal Protein in Young and Older Males
- ClinicalTrials.gov ID
- NCT06091852
- Acronym / sponsor ID
- GutFeeding / METC23-011
- Conditions
- Protein Malabsorption
- Keywords
- Gastrointestinal tract, Intestinal mucosa, Protein, Digestion, Absorption, Aging, Muscle protein synthesis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- FrieslandCampina
- Study start
- 24 Jul 2023 (actual)
- Primary completion
- 5 Apr 2024 (actual)
- Study completion
- 5 Apr 2024 (actual)
- First posted
- 19 Oct 2023 (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.
Rationale: Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion.This anabolic resistance may be related to decreased postprandial amino acid release in the circulation, due to greater amino acid extraction by splanchnic tissues in older individuals. It has been suggested that extracted amino acids are utilized by intestinal epithelial cells for cell proliferation, generating new cells to maintain healthy mucosa. So far, there is no evidence that dietary protein-derived amino acids are taken up and incorporated in intestinal mucosal protein in vivo in humans. Furthermore, there is no evidence that this process is impacted by age.
Objective: To assess the postprandial incorporation of dietary protein-derived amino acids in intestinal mucosal protein in healthy young and older males.
Study design: Cross-sectional, non-therapeutic intervention study design
Study population: 5 healthy, non-obese (BMI 18.5-30kg/m2) young adult males (age: 18-35y inclusive) and 5 community dwelling older males (age: 67+y).
Intervention: Continuous intravenous stable isotope amino acid tracer infusion will be applied, in combination with oral ingestion of 20g intrinsically labelled milk protein, with plasma, muscle and duodenal mucosa biopsy samples collected at different time points throughout the experimental test day.
Main study parameters/endpoints: The primary study outcome is the postprandial (0-5h) incorporation of dietary protein-derived amino acids in duodenal mucosal protein following the ingestion of 20g intrinsically labelled milk protein. Secondary study parameters include postprandial plasma availability of dietary protein-derived amino acids and fractional duodenal mucosal protein synthetic rate.
Detailed description
Skeletal muscle tissue is in a constant state of remodelling, regulated by the balance between tissue protein synthesis and breakdown rates, with a turnover rate of 1-2% per day. It has been well established that protein ingestion is a major anabolic stimulus for muscle protein synthesis. Dietary protein ingestion provides amino acids that stimulate protein synthesis by both functioning as substrate and as signalling molecules that upregulate anabolic pathways.
The anabolic properties of dietary protein largely depend on the protein digestion and amino acid absorption kinetics and subsequent increase in plasma amino acid availability. Following protein ingestion, protein is cleaved into small peptides and amino acids by digestive enzymes. Subsequently, these amino acids are absorbed across the intestinal mucosa by various membrane-bound transporters. The majority of dietary protein derived amino acids is released into the systemic circulation and transported and taken up by various peripheral tissues in the postprandial phase. However, a substantial part of the ingested protein does not become available in the circulation. This part is either not (yet) digested and absorbed, or the absorbed amino acids are taken up by splanchnic tissues, such as the gut and liver, providing precursors for de novo tissue protein synthesis, termed first-pass splanchnic extraction. Previous work in our laboratory has estimated that up to 40% of the protein derived amino acids are taken up and incorporated in the intestinal tract and liver tissues. The intestine is the most highly regenerative organ in the human body, regenerating its epithelium every 3 to 5 days. It has been suggested that the absorbed amino acids are utilized by epithelial cells for rapid cell proliferation, generating new cells to maintain healthy mucosa. Human studies on the incorporation of dietary protein-derived amino acids in intestinal mucosal protein have not been performed. Therefore, the aim of the present explorative in vivo study is to assess, for the first time, the incorporation of dietary protein-derived amino acids in duodenal mucosal protein in humans, and the systemic availability of dietary protein-derived amino acids.
Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion. This proposed anabolic resistance may be related to a decreased postprandial amino acid release in the circulation, due to impairments in protein digestion and amino acid absorption, and greater first-pass splanchnic amino acid extraction in older individuals. Whether dietary protein-derived amino acid incorporation in intestinal mucosal protein is increased with aging remains to be established. Therefore, the current study will use the data on incorporation of dietary protein-derived amino acids in duodenal mucosal protein and postprandial amino acid plasma availability obtained in young and older individuals to evaluate potential age-related differences.
Two primary hypotheses will be tested:
- It is hypothesized that part of the absorbed amino acids will be directly incorporated in duodenal epithelium within 5 hours after protein ingestion.
- It is hypothesized that the extent of postprandial incorporation of dietary protein derived amino acids in duodenal epithelium will be greater in older compared to young males.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Young vs. old
| Arm | Type | Receives |
|---|---|---|
| Intrinsically labelled milk protein | Experimental | Dietary Supplement: Intrinsically labelled milk protein20 grams of protein dissolved in 500 mL of water |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male sex
- Aged 18-35 years or 67+ years
- Body mass index (BMI) between 18.5 and 30 kg/m2
Key exclusion criteria (14 listed)
- History of cardiovascular, respiratory, gastrointestinal, urogenital, neurological, psychiatric, dermatologic, musculoskeletal, metabolic, endocrine, haematological, immunologic disorders, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol, interfere with the execution of the experiment, or potential influence the study outcomes (to be decided by the principal investigator and responsible physician)
- Major abdominal surgery interfering with gastrointestinal function (upon judgement of the principal investigator and responsible physician)
- Use of medication which limit participation in or completion of the study protocol, interferes with the execution of the experiment, or potential influences the study outcomes (to be decided by the principal investigator and responsible physician)
- Use of supplementation (i.e. vitamin, pre- and probiotic supplementation) within 14 days prior to testing
- Administration of investigational drugs or participation in any scientific intervention study in the 14 days prior to the study, which may interfere with this study (upon judgement of the principal investigator and responsible physician)
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 |
|---|---|---|
| Intrinsically labelled milk protein20 grams of protein dissolved in 500 mL of water | Dietary supplement | Intrinsically labelled milk protein |
Primary outcome
Postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein
Time frame: 0-5 hours
Assessed by duodenal mucosal protein-bound [1-13C]-phenylalanine enrichment (expressed as MPE)
Impact of age on postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein
Time frame: 0-5 hours
Assessed by duodenal mucosal protein-bound [1-13C]-phenylalanine enrichment (expressed as MPE) in young and older adults
8 secondary outcomes
Postprandial plasma amino acid concentrations
Time frame: 0-5 hours
Fractional duodenal mucosal protein synthetic rate
Time frame: 0-5 hours
Fractional muscle protein synthetic rate
Time frame: 0-5 hours
Fecal [1-13C]-phenylalanine enrichments (expressed as MPE)
Time frame: Fecal sample of first feces after endoscopy
Fecal nitrogen content
Time frame: Fecal sample of first feces after endoscopy
Fecal microbial metabolites
Time frame: Fecal sample of first feces after endoscopy
Plasma glucose concentrations
Time frame: 0-5 hours
Plasma insulin concentrations
Time frame: 0-5 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 30 Apr 2024.
- Individual participant dataSharing planned: No
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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.
Luc van Loon, Prof principal investigator
Maastricht University Medical Center
Daisy Jonkers, Prof principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intrinsically labelled milk protein in people with Protein Malabsorption, 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 3 inclusion and 14 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 30 Apr 2024. 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?
Postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein (time frame: 0-5 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2024.