Protein Fermentation Unraveled (PROFUN) - Exploring the Relationship Between Digestibility and Metabolite Production

NCT06161155 | Completed DMC

• 1 other identifier: NL84483.091.23
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background of the study: Protein intake is often higher than recommended in Western countries. This leads to increased amounts of protein flowing into the large intestine. Next to increased dietary protein intake, protein digestibility, and endogenous protein losses also affect the amount of protein entering the large intestine. However, these aspects have barely been studied, especially in humans. The large intestine is home to the largest bacterial ecosystem of the body. During the fermentation of protein by these bacteria (microbiota), metabolites are produced such as ammonia, branched-chain fatty acids, biogenic amines, phenolic compounds, indoles, and N-nitroso compounds. There is evidence that some of these metabolites could be harmful for gut epithelia, gastrointestinal health, and health in general after they enter blood circulation. In general, doing measurements inside the gastrointestinal tract is invasive. During this project the protein fermentation will be studied in the gastrointestinal tract using feces and urine, but also in situ using the GISMO GEN1 ingestible. This ingestible contains sensors to measure pH, ammonium, temperature, and redox potential. Objective of the study: The primary objectives of this study are:

1. 1.To investigate the feasibility of the GISMO GEN1 System to monitor biomarkers in the gastrointestinal tract by studying the ingestible transit time, data coverage, participant experience, and serious adverse events (if applicable).
2. 2.To study the effect of a 7-day high versus low digestible protein source present in the diet on protein fermentation in healthy subjects, measured by ammonia concentrations.

Conditions

Protein Fermentation

Keywords

metabolites; dietary protein; digestibility; ingestible

Outcome Measures

Primary Outcomes (2)

• GISMO GEN1 System feasibility

  Ingestible transit time, data coverage, participant experience, and serious adverse events (if applicable)

  3 times approximately 3 days during the trial, within a time frame of 2.5 months

• Ammonia

  Ammonia will be measured in feces, urine, and throughout the gastrointestinal tract using the GISMO GEN1 System.

  3 times during the trial (baseline measurements, dietary intervention 1, dietary intervention 2), within a time frame of 2.5 months

Secondary Outcomes (5)

• Fermentation related metabolites

  3 times during the trial (baseline measurements, dietary intervention 1, dietary intervention 2), within a time frame of 2.5 months

• pH

  3 times during the trial (baseline measurements, dietary intervention 1, dietary intervention 2), within a time frame of 2.5 months

• Microbiome composition

  3 times during the trial (baseline measurements, dietary intervention 1, dietary intervention 2), within a time frame of 2.5 months

• Transit time

  5 times during the trial (1 times during baseline measurements, twice during dietary intervention 1, twice during dietary intervention 2), within a time frame of 2.5 months

• Absorption kinetics

  2 times during the trial (dietary intervention 1, dietary intervention 2), within a time frame of 3 weeks

Study Arms (2)

Whey protein then bovine plasma protein

ACTIVE COMPARATOR

During the first dietary intervention, the diet is supplemented with whey protein isolate. During the second dietary intervention, the diet is supplemented with bovine plasma protein.

Combination Product: Protein digestibility

Bovine plasma protein then whey protein

ACTIVE COMPARATOR

During the first dietary intervention, the diet is supplemented with bovine plasma protein. During the second dietary intervention, the diet is supplemented with whey protein isolate.

Combination Product: Protein digestibility

Interventions

Protein digestibility COMBINATION_PRODUCT

Two protein sources differing in digestiblity will be used in the dietary intervention to create a difference in protein flow into the large intestine, resulting in different levels of protein fermentation. Participants will swallow an ingestible that senses biomarkers related to protein fermentation.

Bovine plasma protein then whey protein; Whey protein then bovine plasma protein

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females
• Age between 16 years or older
• BMI between 18.5-30 kg/m2
• Normal bowel movement: at least one defecation per 48 hours
• Suitable veins for insertion of cannula

You may not qualify if:

• Having a current or past medical history or surgical events that may either put the subject as risk because of participation in the study, or influence the results of the study, including, a swallowing disorder, gastrointestinal or liver or endocrine or renal or cardiovascular disease, any other chronic disease, partial bowel resection, renal failure, cancer, nose/throat diseases, gastric bypass surgery, use of anticoagulants; as determined by the medical supervisor;
• Use of any medications in the week before the study that could substantially alter gastrointestinal motor function (e.g., opioids, prokinetics, anticholinergics, laxatives), or acidity (PPI, H2RA), as determined by medical supervisor;
• Having a bleeding/coagulation disorder, including hemophilia, Von Willebrand disease, Bernard-Soulier, Glanzmann thrombasthenia or thrombocytopenia;
• Swallowing disorders; Among others: dysphagia, any oropharyngeal or oesophageal stricture, functional abnormality, or anxiety disorders related to swallowing disorders;
• Severe dysphagia to food or pills;
• Suspected or known strictures, fistulas, or physiological/mechanical GI obstruction;
• Previous GI abdominal surgery; Except: uncomplicated appendectomy, and/or laparoscopic cholecystectomy;
• Pregnancy, recent childbirth in last 6 months, or actively trying to get pregnant;
• Planned MRI procedure during the study;
• Pacemakers, defibrillator, infusion pump, or other implanted electromedical devices;
• Suffering \>2 times per week from: nausea / vomiting / decreased appetite / abdominal pain / high blood pressure / headaches, shakiness, and weakness / fever / diarrhea / constipation;
• Unwilling to undergo an X-ray examination and/or ultrasound (in case sensorcapsule exit cannot be confirmed);
• Working in a professional healthcare facility (e.g. hospital, dental office, emergency room), military area (e.g. submarine, near radar installation), or heavy industrial area (e.g. power plants, automotive, mining, refineries) during the duration of the study;
• Having an allergy or intolerance towards compounds in the prescribed foods (e.g. gluten, lactose, fish, peanuts, soy, nuts);
• Following a vegetarian or vegan diet;

Sponsors & Collaborators

• Wageningen University: lead
• Stichting IMEC-NL: collaborator

Study Sites (1)

Wageningen University & Research

Wageningen, Gelderland, 6708 WE, Netherlands

Location

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants are masked regarding the protein source in the dietary intervention. Participants are not masked regarding the ingestible.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: After baseline measurements for all participants without dietery intervention, participants will follow a dietary intervention for 7 days followed by a 7-day wash-out period and another 7-day dietary intervention.

Study Record Dates

• First Submitted: October 19, 2023
• First Posted: December 7, 2023
• Study Start: November 21, 2023
• Primary Completion: February 7, 2024
• Study Completion: February 7, 2024
• Last Updated: March 28, 2024

Record last verified: 2024-03

Locations

NL (1)