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Trial registered on ANZCTR


Registration number
ACTRN12621001560886
Ethics application status
Approved
Date submitted
6/10/2021
Date registered
17/11/2021
Date last updated
16/06/2024
Date data sharing statement initially provided
17/11/2021
Date results information initially provided
18/10/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of a dairy based protein complex (IDP®) on stress-induced intestinal barrier dysfunction
Scientific title
The effect of a dairy based protein complex (IDP®) on stress-induced intestinal barrier dysfunction in healthy adults
Secondary ID [1] 305476 0
Ministry of Business Innovation and Employment contract ID - UOAX1902
Universal Trial Number (UTN)
U1111-1270-1747
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Intestinal barrier dysfunction 323857 0
Gut permeability 323858 0
Condition category
Condition code
Diet and Nutrition 321367 321367 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 321370 321370 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At the start of each 14 day treatment period, participants will be provided with 14 stick sachets containing 2 g net weight of dry powder. One stick sachet will be consumed daily, mixed with cold or tepid water.
For the IDP® intervention, the sachets will contain (in order of decreasing concentration): skim milk powder, whole milk powder, IDP® (200 mg), dextrose, and monk fruit extract. IDP® is a patented complex of bioactive milk-proteins, manufactured and commercialised by Quantec Ltd for use in human health applications.

A washout of at least 14 days will occur, before participants complete the second 14 day treatment period.

To ensure adherence to the intervention, participants will be asked to return the stick sachets when they return to the laboratory on day 7 and 14 of each treatment period. Additionally, the researchers will send participants a daily text to check that they have consumed the sachets.
Intervention code [1] 321879 0
Treatment: Other
Comparator / control treatment
A placebo containing skim milk powder, whole milk powder, dextrose, and monk fruit extract will be provided in sachet, Participants will be provided with 14 stick sachets containing 2 g net weight of dry powder. One stick sachet will be consumed daily, mixed with cold or tepid water.
Control group
Placebo

Outcomes
Primary outcome [1] 329145 0
As a measure of gut barrier permeability, urine lactulose to rhamnose will be measured by Liquid Chromatography with tandem mass spectrometry (LC-MS-MS).

Urine will be collected at rest, 24 and 48 hours prior to each treatment period commencing, and after high-intensity exercise on day 14 of the treatment periods. High intensity exercise will involve running at a speed equivalent to 80%VO2peak for 20 minutes. Heart rate will be measured every 5 minutes during the 20 minute run.
Timepoint [1] 329145 0
Analysis will be carried out on urine samples collected after the ingestion of a sugar probe (containing containing 5 g lactulose, 2 g mannitol, and 1 g rhamnose in a total of 450 mL water) 24 and 48 hours before the treatment period and on day 14 of the treatment period.

24 and 48 hours prior to the treatment periods, participants will consume the sugar probe at rest.
On day 14 of the treatment periods, participants will consume the sugar probe immediately upon completion of 20 minutes of high-intensity exercise,

Urine will be collected and pooled over the five hours post-sugar probe ingestion.
Primary outcome [2] 329429 0
As a measure of gut barrier permeability, urine lactulose to mannitol will be measured by Liquid Chromatography with tandem mass spectrometry (LC-MS-MS).
Timepoint [2] 329429 0
Analysis will be carried out on urine samples collected after the ingestion of a sugar probe (containing containing 5 g lactulose, 2 g mannitol, and 1 g rhamnose in a total of 450 mL water) 24 and 48 hours before the treatment period and on day 14 of the treatment period.

24 and 48 hours prior to the treatment periods, participants will consume the sugar probe at rest.
On day 14 of the treatment periods, participants will consume the sugar probe immediately upon completion of 20 minutes of high-intensity exercise,

Urine will be collected and pooled over the five hours post-sugar probe ingestion.
Secondary outcome [1] 401631 0
A modified version of the Gastrointestinal Symptom Rating Scale (Revicki et al. 1997) will be used to assess gastrointestinal discomfort caused by 20 minutes of treadmill running at a speed equivalent to 80%VO2peak

Revicki DA, Wood M, Wiklund I, Crawley J. Reliability and validity of the gastrointestinal symptom
rating scale in patients with gastroesophageal reflux disease. Qual Life Res. 1997 Jan 1;7(1):75–83.
Timepoint [1] 401631 0
Gastrointestinal discomfort will be assessed immediately prior to high intensity exercise, after 10 minutes of high intensity exercise, at the completion of high intensity exercise and 5 hours post ingestion of the sugar probe.

The sugar probe will be ingested immediately after the high-intensity exercise and will contain 5 g lactulose, 2 g mannitol, and 1 g rhamnose in a total of 450 mL water.

Eligibility
Key inclusion criteria
Healthy, active males and females
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Any illness in the four weeks prior to the trial beginning
- Smokers (casual or habitual)
- Any use of non-steroidal anti-inflammatory medication in the four weeks prior to the trial beginning
- Pregnant
- Any lower body musculoskeletal injury or other health conditions/contraindications to exercise
- Gastrointestinal disorder or recent surgery
- Known or suspected allergy to dairy products, starch, gluten, or artificial sweeteners


Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed, numbered, plain packaged stick sachets
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple, balanced randomisation using a randomisation table created by computer software to ensure equal numbers of participants have each treatment in the first and second arms.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A power calculation using the following variables was carried out in G*Power (v 3.1.9.4): power = 0.80, a = 05, n = 18. Based on this calculation, an effect size of 1.0 is expected. This is higher than the effect size (ES = 0.06) reported by Pugh et al (2017) but well below the effect size (ES=4.05) reported by March et al (2017), who used similar protocols to investigate the effects of dietary interventions on gut permeability.

March, D. S., Marchbank, T., Playford, R. J., Jones, A. W., Thatcher, R., & Davison, G. (2017). Intestinal fatty acid-binding protein and gut permeability responses to exercise. European Journal of Applied Physiology, 117(5), 931-941.

Pugh, J. N., Sage, S., Hutson, M., Doran, D. A., Fleming, S. C., Highton, J., ... & Close, G. L. (2017). Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner. European Journal of Applied Physiology, 117(12), 2569-2577.

Data will be analysed using two way (treatment x time) repeated measures ANOVA. If a significant main effect is found, post hoc analysis using Bonferroni adjustment will be carried out. Significance will be set at p<0.05.


Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/12/2021
Actual
21/02/2022
Date of last participant enrolment
Anticipated
29/04/2022
Actual
3/10/2022
Date of last data collection
Anticipated
30/12/2022
Actual
22/09/2023
Sample size
Target
18
Accrual to date
Final
18
Recruitment outside Australia
Country [1] 24169 0
New Zealand
State/province [1] 24169 0
Manawatu-Wanganui

Funding & Sponsors
Funding source category [1] 309833 0
Government body
Name [1] 309833 0
Ministry of Business Innovation and Employment
Country [1] 309833 0
New Zealand
Primary sponsor type
University
Name
Massey University
Address
Private Bag 11-222,
Palmerston North,
4410
Country
New Zealand
Secondary sponsor category [1] 310869 0
Other
Name [1] 310869 0
AgResearch Ltd
Address [1] 310869 0
Lincoln Research Centre,
1365 Springs Road,
Lincoln 7674
Country [1] 310869 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309575 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 309575 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 309575 0
New Zealand
Date submitted for ethics approval [1] 309575 0
26/10/2021
Approval date [1] 309575 0
26/10/2021
Ethics approval number [1] 309575 0

Summary
Brief summary
Disruption of the intestinal barrier and increased intestinal permeability may play a role in chronic intestinal conditions (such as celiac disease, inflammatory bowel disease, and irritable bowel syndrome), as well as pathological or inflammatory states such as obesity, diabetes and rheumatoid arthritis. In healthy individuals, barrier dysfunction can be caused by a number of stressors including endurance exercise, non-steroidal anti-inflammatory drugs, or dietary factors such as emulsifiers in foods. Increased permeability can lead to an inflammatory cascade that exacerbates the loss of barrier function and, if left unmanaged, can lead to poor digestive or systemic health conditions. However, certain dietary factors may improve barrier permeability by supporting digestive and immune health.

This project will investigate whether 14 days of consuming a patented complex of bioactive milk-derived proteins (Immune Defense Proteins (IDP)® ) can mitigate exercise-induced intestinal barrier dysfunction in 18 healthy adults, aged between 18 and 45 years. After 14 days of supplementation with either IDP or a placebo, participants will undertake 20 minutes of high-intensity running before ingesting a sugar solution. Urine will then be collected over 5 hours and analysed for markers of gut permeability. After a 14 day washout, participants will complete the same protocol using the opposite treatment (IDP or placebo).

We hypothesise that 14 days of consuming IDP will reduce the increase in intestinal permeability caused by exercise stress in healthy adults.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114638 0
A/Prof Matthew Barnes
Address 114638 0
School of Sport, Exercise and Nutrition,
Crn Albany Drive and Collinson Rd,
Massey University,
Palmerston North,
4472
Country 114638 0
New Zealand
Phone 114638 0
+64 6 3569099
Fax 114638 0
Email 114638 0
[email protected]
Contact person for public queries
Name 114639 0
A/Prof Matthew Barnes
Address 114639 0
School of Sport, Exercise and Nutrition,
Crn Albany Drive and Collinson Rd,
Massey University,
Palmerston North,
4472
Country 114639 0
New Zealand
Phone 114639 0
+64 6 3569099
Fax 114639 0
Email 114639 0
[email protected]
Contact person for scientific queries
Name 114640 0
A/Prof Matthew Barnes
Address 114640 0
School of Sport, Exercise and Nutrition,
Crn Albany Drive and Collinson Rd,
Massey University,
Palmerston North,
4472
Country 114640 0
New Zealand
Phone 114640 0
+64 6 3569099
Fax 114640 0
Email 114640 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
For ethical reasons, no individualised data will be reported. Data will be presented as group mean and standard deviations.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYeshttps://doi.org/10.1007/s00421-024-05423-4 Ulluwishewa, D., Nicholls, G., Henderson, H. et al... [More Details]

Documents added automatically
No additional documents have been identified.