The Incorporation of Dietary Protein-Derived Amino Acids in Duodenal Epithelium

NCT06091852 | Completed DMC

• 1 other identifier: METC23-011
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Protein Malabsorption

Keywords

Gastrointestinal tract; Intestinal mucosa; Protein; Digestion; Absorption; Aging; Muscle protein synthesis

Outcome Measures

Primary Outcomes (2)

• 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)

  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

  0-5 hours

Secondary Outcomes (8)

• Postprandial plasma amino acid concentrations

  0-5 hours

• Fractional duodenal mucosal protein synthetic rate

  0-5 hours

• Fractional muscle protein synthetic rate

  0-5 hours

• Fecal [1-13C]-phenylalanine enrichments (expressed as MPE)

  Fecal sample of first feces after endoscopy

• Fecal nitrogen content

  Fecal sample of first feces after endoscopy

Other Outcomes (9)

• Age in years

  Baseline

• Body weight in kg

  Baseline

• Height in m

  Baseline

Study Arms (1)

Intrinsically labelled milk protein

EXPERIMENTAL

20 grams of protein dissolved in 500 mL of water

Dietary Supplement: Intrinsically labelled milk protein

Interventions

Intrinsically labelled milk protein DIETARY_SUPPLEMENT

20 grams of protein dissolved in 500 mL of water

Intrinsically labelled milk protein

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male sex
• Aged 18-35 years or 67+ years
• Body mass index (BMI) between 18.5 and 30 kg/m2

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• FrieslandCampina: collaborator

Study Sites (1)

Maastricht University Medical Center+

Maastricht, 6229ER, Netherlands

Location

Study Officials

• Luc van Loon, Prof

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

• Daisy Jonkers, Prof

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Young vs. old

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: October 19, 2023
• Study Start: July 24, 2023
• Primary Completion: April 5, 2024
• Study Completion: April 5, 2024
• Last Updated: April 30, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)