Protein Digestion and Amino Acid Absorption in the Aging Gastrointestinal Tract

NCT06553794 | Completed DMC

• 1 other identifier: METC23-029
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Worldwide, the aging population is increasing. Aging is associated with loss of independence and increased risk of co-morbidity. Sufficient protein intake is imperative to maintain skeletal muscle mass and overall health, and thereby stimulates active aging. It has been suggested that age-dependent changes in gastrointestinal (GI) tract physiology affect the amount of protein digested and absorbed, as well as the intestinal microbiota. However, it is not clear to what extent actual protein digestion and absorption are altered in older individuals. So far, no human data on the expression and activity of brush border enzymes and protein-related transporters in small intestinal epithelial cells are available. Understanding the age-dependent digestion and absorption kinetics of protein is important for creating specific diets in older individuals to improve protein intake and thereby stimulate healthy aging. Objective: To assess the effects of aging on protein digestion and amino acid absorption in healthy humans in vivo. Study design: Cross-sectional Study population: 12 healthy, non-obese (BMI 18.5-30kg/m2) young adults (age: 18-35 y inclusive) and 12 community dwelling older adults (age: ≥67 y). Intervention: Subjects will undergo a standardized heavy water dosing protocol for 2 days (1 "loading day", 1 "maintenance day"). Blood and saliva sampling will be conducted throughout the heavy water dosing protocol to determine body water and amino acid enrichment levels. On the experimental test day, a gastroscopy with collection of duodenal mucosa tissue samples will be performed to allow assessment of the expression and activity of brush border enzymes and protein-related transporters, and to determine fractional duodenal mucosal protein synthesis rate. Fecal samples will be collected at baseline and after the gastroscopy. Main study parameters/endpoints: The primary study parameter is the mRNA expression of brush border enzymes and small peptide and amino acid transporters in duodenal mucosal cells. Secondary study parameters include protein expression of brush border enzymes and small peptide and amino acid transporters in duodenal mucosal cells, fecal microbial fermentation metabolites and duodenal mucosal protein synthesis rate.

Conditions

Protein Malabsorption

Keywords

Protein; Digestion; Absorption; Intestinal mucosa; Aging

Outcome Measures

Primary Outcomes (1)

• Gene expression of brush border enzymes and protein-related transporters in duodenal mucosal cells

  as determined by real-time polymerase chain reaction (PCR)

  day 3 of study period

Secondary Outcomes (5)

• Protein expression of brush border enzymes and protein-related transporters

  day 3 of study period

• Microbial proteolytic fermentation metabolites involved in protein metabolism

  Baseline

• Fractional duodenal mucosal protein synthetic rate

  during study period (3 days)

• Fecal elastase

  Baseline

• Plasma citrulline

  Baseline

Other Outcomes (5)

• Age in years

  Baseline

• Body weight in kg

  Baseline

• Height in m

  Baseline

Study Arms (1)

Non-therapeutic intervention

EXPERIMENTAL

Subjects will undergo a standardized heavy water dosing protocol for 2 days (1 "loading day", 1 "maintenance day") and consume a standardized diet for 2 days. On the experimental test day, a gastroscopy with collection of duodenal mucosa tissue samples will be performed.

Other: Gastroscopy with duodenal mucosal tissue biopsies

Interventions

Gastroscopy with duodenal mucosal tissue biopsies OTHER

Subjects will undergo a standardized heavy water dosing protocol for 2 days (1 "loading day", 1 "maintenance day") and consume a standardized diet for 2 days. On the experimental test day, a gastroscopy with collection of duodenal mucosa tissue samples will be performed.

Non-therapeutic intervention

Eligibility Criteria

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

You may qualify if:

• Aged 18-35 years or 67+ years
• Body mass index (BMI) between 18.5 and 30 kg/m2
• Regular stool frequency ranging from 1-3 times/day

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. protein, vitamin, pre- and probiotic supplementation) within 14 days prior to testing
• Administration of investigational drugs or participation in any scientific intervention study prior or during 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
• Excessive alcohol consumption (defined as \> 14 alcoholic consumptions per week)
• Smoking
• Drug use
• Pregnancy
• Lactation
• Donated blood three months prior to the test day
• 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

Maastricht, Maastricht, Netherlands

Location

MeSH Terms

Interventions

Gastroscopy

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Daisy Jonkers, Prof

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

• Luc van Loon, 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

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: August 14, 2024
• Study Start: August 20, 2024
• Primary Completion: June 13, 2025
• Study Completion: June 13, 2025
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)