search
Back to results

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

Primary Purpose

Protein Malabsorption

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Intrinsically labelled milk protein
Sponsored by
Maastricht University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Protein Malabsorption focused on measuring Gastrointestinal tract, Intestinal mucosa, Protein, Digestion, Absorption, Aging, Muscle protein synthesis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • Maastricht University Medical Center+Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intrinsically labelled milk protein

Arm Description

20 grams of protein dissolved in 500 mL of water

Outcomes

Primary Outcome Measures

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)
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

Secondary Outcome Measures

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
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
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
Fecal [1-13C]-phenylalanine enrichments (expressed as MPE)
Fecal protein excretion, assessed by fecal [1-13C]-phenylalanine enrichments (expressed as MPE)
Fecal nitrogen content
Fecal protein excretion, assessed by fecal nitrogen content
Fecal microbial metabolites
Microbial metabolites, including short-chain fatty acids, assessed by analyzing fecal samples
Plasma glucose concentrations
Plasma glucose concentrations
Plasma insulin concentrations
Plasma insulin concentrations

Full Information

First Posted
June 27, 2023
Last Updated
October 18, 2023
Sponsor
Maastricht University Medical Center
Collaborators
FrieslandCampina
search

1. Study Identification

Unique Protocol Identification Number
NCT06091852
Brief Title
The Incorporation of Dietary Protein-Derived Amino Acids in Duodenal Epithelium
Acronym
GutFeeding
Official Title
The Incorporation of Dietary Protein-Derived Amino Acids in Duodenal Mucosal Protein in Young and Older Males
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 24, 2023 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University Medical Center
Collaborators
FrieslandCampina

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Protein Malabsorption
Keywords
Gastrointestinal tract, Intestinal mucosa, Protein, Digestion, Absorption, Aging, Muscle protein synthesis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Young vs. old
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intrinsically labelled milk protein
Arm Type
Experimental
Arm Description
20 grams of protein dissolved in 500 mL of water
Intervention Type
Dietary Supplement
Intervention Name(s)
Intrinsically labelled milk protein
Intervention Description
20 grams of protein dissolved in 500 mL of water
Primary Outcome Measure Information:
Title
Postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein
Description
Assessed by duodenal mucosal protein-bound [1-13C]-phenylalanine enrichment (expressed as MPE)
Time Frame
0-5 hours
Title
Impact of age on postprandial incorporation of dietary protein-derived amino acids in duodenal mucosal protein
Description
Assessed by duodenal mucosal protein-bound [1-13C]-phenylalanine enrichment (expressed as MPE) in young and older adults
Time Frame
0-5 hours
Secondary Outcome Measure Information:
Title
Postprandial plasma amino acid concentrations
Description
Appearance of milk protein-derived amino acids in plasma over the full assessment period (5 h), as determined using stable isotope tracer methodology
Time Frame
0-5 hours
Title
Fractional duodenal mucosal protein synthetic rate
Description
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
Time Frame
0-5 hours
Title
Fractional muscle protein synthetic rate
Description
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
Time Frame
0-5 hours
Title
Fecal [1-13C]-phenylalanine enrichments (expressed as MPE)
Description
Fecal protein excretion, assessed by fecal [1-13C]-phenylalanine enrichments (expressed as MPE)
Time Frame
Fecal sample of first feces after endoscopy
Title
Fecal nitrogen content
Description
Fecal protein excretion, assessed by fecal nitrogen content
Time Frame
Fecal sample of first feces after endoscopy
Title
Fecal microbial metabolites
Description
Microbial metabolites, including short-chain fatty acids, assessed by analyzing fecal samples
Time Frame
Fecal sample of first feces after endoscopy
Title
Plasma glucose concentrations
Description
Plasma glucose concentrations
Time Frame
0-5 hours
Title
Plasma insulin concentrations
Description
Plasma insulin concentrations
Time Frame
0-5 hours
Other Pre-specified Outcome Measures:
Title
Age in years
Description
Reported by participants
Time Frame
Baseline
Title
Body weight in kg
Description
Scale
Time Frame
Baseline
Title
Height in m
Description
Stadiometer
Time Frame
Baseline
Title
BMI in kg/m2
Description
Calculated from height and body weight
Time Frame
Baseline
Title
Skeletal muscle mass
Description
Bioelectrical impedance analysis
Time Frame
Baseline
Title
Fat mass
Description
Bioelectrical impedance analysis
Time Frame
Baseline
Title
Dietary macronutrient intake
Description
Assessed by written dietary intake records
Time Frame
2 days prior to experimental trial day
Title
Systolic blood pressure in mmHg
Description
Electrical sphygmomanometer
Time Frame
Baseline
Title
Diastolic blood pressure in mmHg
Description
Electrical sphygmomanometer
Time Frame
Baseline

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male sex Aged 18-35 years or 67+ years Body mass index (BMI) between 18.5 and 30 kg/m2 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lisa ME Kuin, MD
Phone
+31 88 388 7271
Email
lisa.kuin@maastrichtuniversity.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luc van Loon, Prof
Organizational Affiliation
Maastricht University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Daisy Jonkers, Prof
Organizational Affiliation
Maastricht University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maastricht University Medical Center+
City
Maastricht
ZIP/Postal Code
6229ER
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa ME Kuin, MD
Phone
+31 88 388 7271
Email
lisa.kuin@maastrichtuniversity.nl
First Name & Middle Initial & Last Name & Degree
Daisy Jonkers, Prof.
First Name & Middle Initial & Last Name & Degree
Luc van Loon, Prof.
First Name & Middle Initial & Last Name & Degree
Lisa Kuin, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs