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Trial registered on ANZCTR


Registration number
ACTRN12611000740998
Ethics application status
Approved
Date submitted
13/07/2011
Date registered
14/07/2011
Date last updated
5/02/2020
Date data sharing statement initially provided
5/02/2020
Date results information initially provided
5/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative effects of A1 versus A2 milk on gastrointestinal symptoms and systemic exposure to beta-casomorphin-7 (BCM7)
Scientific title
Adults and the effect of A1 versus A2 milk consumption on gastrointestinal symptoms and systemic exposure to beta-casomorphin-7 (BCM7)
Secondary ID [1] 262621 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gastrointestinal symptoms related to milk intolerance 268317 0
Condition category
Condition code
Oral and Gastrointestinal 268448 268448 0 0
Normal oral and gastrointestinal development and function
Diet and Nutrition 268455 268455 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a randomised, crossover study over an 8 week period consisting of 2 weeks of an initial washout. Following washout, 40 participants will be randomised to either the A1 milk or A2 milk group (Crossover 1), with 20 in each group. This is then followed by another 2 weeks washout after which Subjects will then start the alternative A1 or A2 milk Intervention for another 2 weeks intervention (crossover2).

During washout, participants will consume their normal diet (excluding all dairy) and use rice milk and rice yoghurt alternatives to replace habitual daily dairy intake.

Intervention consists of either:
1) a normal diet (excluding all dairy) + 750mL A2 beta-casein protein containing milk consumed in 3 serves daily (~7-8g A2 type beta-casein/day)
or
2) Normal diet (excluding all dairy) + 750mL A1 containing milk per day, which is equivalent to ~7-8g A1 type beta-casein/day;

Milk will be given as UHT long life, skim milk (A2 Dairy Products Australia)
Average composition:
energy 189kJ/100mL
total protein 3.1g/100mL
total fat 0.1g/100mL
carbohydrate (including lactose) 5.2g/100mL
Intervention code [1] 266968 0
Treatment: Other
Comparator / control treatment
Normal diet (excluding all dairy) + 750mL A1 beta-casein protein containing milk consumed in 3 serves daily (~7-8g A1 type beta-casein/day) for 2 weeks. Milk will be given as UHT long life, reduced fat milk (A2 Dairy Products Australia) Average composition: energy 189kJ/100mL total protein 3.1g/100mL total fat 2.5g/100mL carbohydrate (including lactose) 5.2g/100mL
Control group
Active

Outcomes
Primary outcome [1] 269204 0
Gastrointestinal symptom management.
Participants will record gastrointestinal symptoms of intolerance in their Symptom Report Diary and daily bowel movement frequency/stool consistency using the Bristol Stool Scale.
Timepoint [1] 269204 0
Symptoms recorded during each 2 week intervention period
Secondary outcome [1] 279113 0
Investigation of the presence of BCM-7 in serum from fasting and postprandial blood samples
Timepoint [1] 279113 0
At the beginning and end of each 2 week intervention period
1 hour postprandial sample after consumption of 500mL of milk intervention at the end of each 2 week intervention period
Secondary outcome [2] 279114 0
Measurement of gastrointestinal tract permeability from a dual sugar test and urine analysis
Timepoint [2] 279114 0
At the end of each 2 week intervention period
Secondary outcome [3] 279138 0
Measurement of gut inflammation from analysis of faecal calprotectin to investigate possible precursors to BCM-7 effects
Timepoint [3] 279138 0
At the end of each 2 week intervention period

Eligibility
Key inclusion criteria
Caucasian
Do not drink more than 1 serve milk/day
Those who report lactose intolerance but have not received medial diagnosis
Willing to consume milk for 8 weeks
Able to sign and understand informed consent
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Milk allergy
Diagnosed lactose intolerance
Pregnancy and lactation
Cardiovascular event in the last 6 months
Current, habitual opioid consumption
Antibiotic treatment within the last 8 weeks prior to screening
Immunosuppressive medications or anti-inflammatory drugs within the last 4 weeks prior to screening

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)
Potential participants will be screened and attend a briefing session to assess suitability. Suitable participants will be allocated to a group by central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer program generated randomisation plan
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 267447 0
Commercial sector/Industry
Name [1] 267447 0
A2 Dairy Products Australia
Address [1] 267447 0
Kew Executive Suites
Locked Bag 8000, MDC, Kew,Victoria 3102
Country [1] 267447 0
Australia
Primary sponsor type
University
Name
Curtin University of Technology
Address
GPO Box U1987
Perth, Western Australia 6845
Country
Australia
Secondary sponsor category [1] 266489 0
None
Name [1] 266489 0
Address [1] 266489 0
Country [1] 266489 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269414 0
Curtin University Human Ethics Committee
Ethics committee address [1] 269414 0
GPO Box U1987
Perth WA 6845
Ethics committee country [1] 269414 0
Australia
Date submitted for ethics approval [1] 269414 0
15/07/2011
Approval date [1] 269414 0
04/10/2011
Ethics approval number [1] 269414 0
HR102/2011

Summary
Brief summary
At present there is debate surrounding the effects of the A1 variant (A1) of the beta-casein protein contained in bovine milk compared to the progenitor A2 variant (A2) in terms of potential health outcomes. However, there is evidence to suggest that the beta-casein composition of milk can have an impact on gastrointestinal symptoms of intolerance which may be due to exposure to A1 beta-casein derived digestion products. Given the Australian Dietary Guidelines recommend the consumption of at least 2-3serves of dairy foods per day, the effects of milk variety on digestive function and exposure to beta-casein digestion products is important and warrants investigation. Most available milk and milk products contain comparable amounts of both A1 and A2, protein variants which are reported to have potential differences in bioactivity upon digestion. This stems from the release of the seven amino acid opioid peptide, termed beta-casomorphin-7 (BCM-7) from the digestion of A1 but not A2 beta-casein. However, further research is required to demonstrate clearly any differential in vivo effects between A1 and A2 beta-casein consumption on biological responses, including those associated with gastrointestinal symptoms of milk intolerance. The general aim of this blinded, cross-over trial is to demonstrate that A2 beta-casein containing milk will have a neutral effect on gastrointestinal symptoms and exposure to BCM-7 relative to A1 beta-casein containing milk.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32870 0
A/Prof Sebely Pal
Address 32870 0
School of Public Health Curtin University GPO Box U1987 Perth WA 6845
Country 32870 0
Australia
Phone 32870 0
+61 8 9266 4755
Fax 32870 0
Email 32870 0
s.pal@curtin.edu.au
Contact person for public queries
Name 16117 0
A/Prof Assoc Prof Sebely Pal
Address 16117 0
School of Public Health
Curtin University
GPO Box U1987
Perth WA 6845
Country 16117 0
Australia
Phone 16117 0
+61 8 9266 4755
Fax 16117 0
Email 16117 0
s.pal@curtin.edu.au
Contact person for scientific queries
Name 7045 0
A/Prof Assoc Prof Sebely Pal
Address 7045 0
School of Public Health
Curtin University
GPO Box U1987
Perth WA 6845
Country 7045 0
Australia
Phone 7045 0
+61 8 9266 4755
Fax 7045 0
Email 7045 0
s.pal@curtin.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data sharing was not part of the planning for this project
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 6785 0
Published September 2014, Epub 2014 Jul 2.
Ho, S., Woodford, K., Kukuljan, S. Pal, S. 2014. Comparative Effects of A1 Versus A2
Beta-Casein on Gastrointestinal Measures: a Blinded Randomised Cross-Over Pilot
Study. European Journal of Clinical Nutrition. 68: pp. 994-1000.
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary