Condition category
Digestive System
Date applied
12/12/2014
Date assigned
21/01/2015
Last edited
19/01/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
It is commonly assumed that the proteins that we eat in our diet are broken down by the digestive system into organic compounds called amino acids. However, recently the focus has switched towards a view in which small amounts of intact protein and peptides do enter the circulation. What molecules pass from the digestive system to the circulation depends on so-called intestinal permeability, where the intestine allows nutrients pass though the gut wall while acting as a barrier to keep potentially harmful substances, such as bacteria, from passing through to the general circulation. Current research into intestinal permeability to proteins has focussed on its role in a number of different conditions including Crohn’s disease, celiac disease and inflammatory bowel disease . Little research has been done with regard to the uptake of proteins and peptides (fragments of proteins) under different degrees of intestinal permeability and their biological relevance in a healthy population. Here, we want to look at the effect of exercise-induced permeability on the amount of casein (a type of protein found in milk) and casein-derived peptides available in the blood (plasma bioavailability). We also want to compare intestinal permeability to simple sugars with intestinal permeability to casein and casein-derived peptides. Lastly, we plan to study the effect of exercise-induced permeability on markers of inflammation, exercise metabolism, and function of the digestive system (gastro-intestinal function).

Who can participate?
Men aged between 18-35 that cycle at least twice a week, with a body mass of 20-25 kg/m2.

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 (intervention) drink a multisugar solution just before starting a two day exercise test. Those in group 2 (control) drink the multisugar solution but do not do any exercise.The exercise test consists of two parts. The first part is performed in the evening and involves exercise that is meant to use up the body’s glycogen (energy) stores. The second part is performed after an overnight fast and involves 90min cycling at 50% of the maximal capacity of each participant (calculated using Wmax and VO2max) . The gut barrier function of all participants are measured by collecting urine and blood just before group 1 start the exercise test and then at regular intervals for the next 5 hours after the exercise test. Sugars, casein-derived amino acids and other compounds (related to energy metabolism, immune system and inflammation) are measured from the collected urine and plasma. One more blood sample is taken from all participants 24 hours after the exercise test is complete for group 1 participants and after an overnight fast. This complete three-day-protocol is repeated one week later with the control and intervention groups swapped around to see whether the results are reproducible.

What are the possible benefits and risks of participating?
There is no direct health-related benefit for the subjects, but for the subjects the measurement of the Wmax and VO2max is of great value, because they can use it to improve and optimize their training program and progress. Subjects completing the study will receive financial compensation of €220. There are minor risks for the subjects during this study. People most at risk of allergic reactions are excluded from participating. The exercise the subjects will have to perform is severe and will result in fatigue, and can give rise to some muscle soreness afterwards, but this intensity is needed to ensure a reaction on intestinal permeability and immunity. The intensity of the exercise will be well-tolerated in the participants chosen i.e. trained athletes. There is a small risk of bruising regarding the blood sampling procedures.

Where is the study run from?
Wageningen University (Netherlands)

When is the study starting and how long is it expected to run for?
June 2013 to December 2013

Who is funding the study?
Wageningen University and Research Centre (Netherlands)

Who is the main contact?
Ms Lonneke JanssenDuijghuijsen
lonneke.janssen@wur.nl

Trial website

Contact information

Type

Public

Primary contact

Ms Lonneke JanssenDuijghuijsen

ORCID ID

http://orcid.org/0000-0002-9516-6681

Contact details

Bornse Weilanden 9
Wageningen
6708 WG
Netherlands

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NL44947.081.13

Study information

Scientific title

The effect of intense exercise on intestinal permeability and protein and peptide levels in plasma of healthy men

Acronym

Protégé

Study hypothesis

1. The primary objective is to study the effect of exercise-induced permeability on plasma bioavailability of casein and casein-derived peptides, and to evaluate its reproducibility.
2. The secondary objective is to compare intestinal permeability to simple sugars with intestinal permeability to casein and casein-derived peptides.
3. The tertiary objective is to study the effect of exercise-induced permeability on markers of inflammation, exercise metabolism, and gastro-intestinal function.

Ethics approval

Wageningen University Medical Ethical Testing Committee (METC-WU), 23/09/2013, ref: 13/10; NL44947.081.13

Study design

This intervention study comprises of an exercise trial with cross-over design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a participant information sheet

Condition

Intestinal permeability

Intervention

Each participant is his own control. On the first day participants came in fasted overnight (=resting condition) and ingested a sugar probe solution containing 5 grams lactulose, 1 gram L-rhamnose, and 0.5 gram D-Xylose. Next to this, they ingested a protein solution containing 40 grams of sodium caseinate. Hereafter, urine and blood was sampled at regular intervals over a period of 5 hours. On the evening of the first day (after dinner), the participants came back for the first part of the exercise test consisting of a 2min blocks interval training on a cycle ergometer, alternating between 90% and 50% of their maximal capacity for as long as they could keep up. On the second day, the participants came back in the morning, again after being fasted overnight. They completed the second part of the exercise test consisting of 90 min cycling at 50% of their maximal capacity. Afterwards (=post-exercise condition) the sugar probe solution as well as the casein protein solution was ingested and again blood and urine was sampled at regular intervals for 5 hours. On the third day, the participants came back in the morning, again after being fasted overnight. One single blood sample was drawn.
This complete three-day-protocol was repeated one week later.

Intervention type

Mixed

Phase

Drug names

Primary outcome measures

Plasma casein and casein-derived peptide levels with and without exercise-induced permeability of the gastrointestinal tract.

Plasma samples are taken at t=0, 15, 30, 60, 90, 120, and 300min after intake of casein directly after the control condition (no exercise) or the 1.5hr cycling test. Levels of casein and casein-derived peptides will be analysed in these plasma samples with ELISA and UPLC-MS/MS.

Secondary outcome measures

1. Intestinal permeability as assessed by multisugar test
Subjects will receive a multisugar solution to assess permeability directly after the control condition (no exercise) or the 1.5hr cycling test. Urine will be collected for 5 hours at hourly intervals after intake. Urinary sugar levels will be analyzed with HPLC
2. Health effects of exercise-induced permeability and plasma casein and casein-derived peptides

Other parameters: serum parameters of inflammation, exercise metabolism, and gastrointestinal function.

Overall trial start date

14/06/2013

Overall trial end date

20/12/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male cyclists/triathletes with at least two years of cycling experience
2. Cycling at least two times a week during peak season
3. 18-35 years old
4. Body mass index (BMI) 20-25 kg/m2
5. Meeting criteria of valid max-test
6. Suitable veins for blood sampling

Participant type

Healthy volunteer

Age group

Adult

Gender

Male

Target number of participants

12

Participant exclusion criteria

1. Known symptoms of milk allergy
2. Known symptoms of immune disease, such as diabetes, gastritis, and coeliac disease
3. Known symptoms of intestinal disease, such as Crohn’s Disease, ulcerosis, and irritable bowel syndrome
4. Smoking
5. Use of hard drugs
6. Chronic use of NSAIDs: aspirins, ibuprofen, etc.
7. Using medicines for gastric and/or intestinal function
8. Participation in other scientific studies
9. Blood donation during the last six weeks before the start of the study

Recruitment start date

23/09/2013

Recruitment end date

08/11/2013

Locations

Countries of recruitment

Netherlands

Trial participating centre

Wageningen University
Wageningen
6708 PB
Netherlands

Sponsor information

Organisation

Wageningen University and Research Centre

Sponsor details

Droevendaalsesteeg 4
Wageningen
6708 PB
Netherlands

Sponsor type

University/education

Website

http://www.wageningenur.nl/nl/Onderzoek-Resultaten/Projecten-EZ/Expertisegebieden/Kennisbasis-onderzoek/Gezond-en-veilig-voedsel-in-ketenperspectief/IPOPcustomized-nutrition-3.htm

Funders

Funder type

University/education

Funder name

Wageningen University and Research Centre

Alternative name(s)

Wageningen UR, WUR

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

Netherlands

Results and Publications

Publication and dissemination plan

Researchers intend to first publish the results on the effect of exercise on the sugar probe and casein protein test. At this stage it is not known what will happen with other results obtained within this human trial.

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes