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Trial registered on ANZCTR


Registration number
ACTRN12616001694404
Ethics application status
Approved
Date submitted
29/11/2016
Date registered
9/12/2016
Date last updated
26/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
a2 Milk for gut comfort
Scientific title
In young dairy intolerant women, compared with dairy tolerant women, does the ingestion of A1 beta-casein free milk or lactose free milk compared to conventional milk (containing lactose, A1 and A2 beta- casein) improve digestibility and reduce gastric inflammation?
Secondary ID [1] 290349 0
Nil
Universal Trial Number (UTN)
Trial acronym
aMiGo
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Impaired digestion 300630 0
Condition category
Condition code
Diet and Nutrition 300479 300479 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 301011 301011 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
750 ml of milk to be consumed on three different occasions separated by 1 week of wash out period between the milk ingestion. Subjects will be fasted overnight prior to each intervention arm. The milk will be consumed in full in the presence of the researchers to confirm compliance, to be ingested within 10 minutes. No additionally food or drink will be consumed during the 3 hour intervention. The milks to be consumed are
(1) Conventional milk (A1+A2 beta-casein)
(2) a2 milk (only A2 beta-casein) and
(3) Lactose free milk (A1+A2 beta-casein).

Intervention code [1] 296165 0
Lifestyle
Comparator / control treatment
Conventional milk
Control group
Active

Outcomes
Primary outcome [1] 299925 0
Analysis of digestive symptoms scores by a 10 cm Visual Analog Scale (VAS)
Timepoint [1] 299925 0
Prior to drink ingestion (two baseline assessments to account for individual variation at 15 minutes and 5 minutes prior to ingestion), immediately following ingestion and at 30 min intervals for 3 hrs at each visit.
Secondary outcome [1] 328499 0
Differences in plasma insulin concentrations measured by radio-immunoassay array after milk ingestion
Timepoint [1] 328499 0
Baseline and hourly for 3 hrs at each visit.
Secondary outcome [2] 328531 0
Measure lactase production SNPs (e.g. LCT -13910, LCT-22018) to determine lactase persistence genotype from collected blood samples.
Timepoint [2] 328531 0
Baseline
Secondary outcome [3] 328532 0
Whole blood counts to evaluate changes in white blood cell populations in response to milk ingestion as a measure of immune activation.
Timepoint [3] 328532 0
Baseline, 1 and 2 hrs post milk ingestion at each visit.
Secondary outcome [4] 328533 0
Difference in plasma glucose level using a Roche Cobas c311 autoanalyser by enzymatic colorimetric assay.
Timepoint [4] 328533 0
Baseline and at 30 mins interval for 3 hrs post ingestion at each visit.
Secondary outcome [5] 328534 0
Changes in urinary creatinine using a Roche Cobas c311 autoanalyser by enzymatic colorimetric assay and galactose using enzymatic spectrophotometric assay.
Timepoint [5] 328534 0
Baseline and continuous over 3 hrs post ingestion at each visit.
Secondary outcome [6] 328535 0
Imaging of intestinal motility will be assessed using MRI on a subset of subjects (n=5 per subject group)
Timepoint [6] 328535 0
Baseline and up to 5 times post ingestion over 3 hrs.
Secondary outcome [7] 328536 0
RNA extraction to measure changes in inflammatory gene expression (including TNF-a, MCP-1, IL-1beta) in peripheral blood mononuclear cells taken from blood samples. These will be assessed by RT-PCR.
Timepoint [7] 328536 0
Fasting samples and at 1 & 2 hours following milk ingestion at each visit.
Secondary outcome [8] 328537 0
Changes in plasma lipids analysed by Roche Cobas c311 autoanalyser by enzymatic colorimetric assay.
Timepoint [8] 328537 0
At baseline and every 30 mins post milk ingestion at each visit.
Secondary outcome [9] 328539 0
Assess gastrointestinal symptoms using Live Gastrointestinal Symptoms diary (LGS) as they occur. Any bowel movements with a Bristol Stool Scale through self-assessment and photograph comparison.
Timepoint [9] 328539 0
Diarrhoea and abdominal pain over 12 hrs following milk ingestion at each visit.
Secondary outcome [10] 328553 0
Differences in inflammatory circulating cytokines (including CRP, TNF-a, MCP-1) assessed by flow cytometric multiplex array (Milliplex (Registered Trademark) MAP Kit Human Metabolic Hormone Magnetic Bead Panel Assay, Millipore, MO, USA)
Timepoint [10] 328553 0
Baseline and hourly for 3 hours post milk ingestion at each visit.
Secondary outcome [11] 328554 0
Differences in breath metabolites (H2, CH4 and breath volatiles) by GC -MS.
Timepoint [11] 328554 0
Baseline and every 15 min for 3 hrs at each visit.

Eligibility
Key inclusion criteria
Female aged 20-30years
Healthy BMI (18-28kg/m2)
No history of gastrointestinal disease or metabolic disease

Minimum age
20 Years
Maximum age
30 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Allergy to dairy (clinical diagnosis of antibody-mediated milk allergy)
Medical history of gastrointestinal disease: celiac, IBS, Crohns and colitis.
Fail to produce breath H2 >20ppm after a lactulose challenge.
Medical history precluding a healthy state: history of myocardial infarction, angina, stroke, cancer or pre-existing diabetes,
Self reported alcohol intake exceeding a moderate intake (>28 units per week).



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)
Allocation to the intervention sequence will be concealed through use of sealed envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatment randomisation by using a randomization table created by a computer software
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
We would expect a standard deviation of 0.8 using total VAS of intestinal comfort symptoms Using n=10 per group would give 80% power of detecting between-treatment difference in total VAS of 1.1,

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 outside Australia
Country [1] 8330 0
New Zealand
State/province [1] 8330 0
Auckland

Funding & Sponsors
Funding source category [1] 294740 0
Commercial sector/Industry
Name [1] 294740 0
AgResearch Ltd.
Address [1] 294740 0
Grasslands Research Centre
Tennet Drive
Palmerston North
Postcode: 4442
Country [1] 294740 0
New Zealand
Funding source category [2] 295128 0
Commercial sector/Industry
Name [2] 295128 0
The a2 Milk Company Limited
Address [2] 295128 0
The a2 Milk Company Ltd
Level 1, 122 Quay Street
Auckland
Postcode: 1010
Country [2] 295128 0
New Zealand
Primary sponsor type
University
Name
University Of Auckland
Address
University of Auckland Research Office
Level 10, Building 620
49 Symonds Street
Suburb/Town: Aucklnad
Postcode: 1010
Country
New Zealand
Secondary sponsor category [1] 293588 0
Commercial sector/Industry
Name [1] 293588 0
AgResearch Ltd.
Address [1] 293588 0
Grasslands Research Centre
Tennet Drive
Palmerston North
Postcode: 4442
Country [1] 293588 0
New Zealand
Secondary sponsor category [2] 293589 0
Commercial sector/Industry
Name [2] 293589 0
The a2 Milk Company Ltd
Address [2] 293589 0
The a2 Milk Company Ltd
Level 1, 122 Quay Street
Auckland
Postcode: 1010
Country [2] 293589 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296157 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 296157 0
Ministry of Health
Ethics Department
Freyberg Building
Reception – Ground Floor
20 Aitken Street
Wellington 6011
New Zealand
Ethics committee country [1] 296157 0
New Zealand
Date submitted for ethics approval [1] 296157 0
19/10/2016
Approval date [1] 296157 0
09/12/2016
Ethics approval number [1] 296157 0
16/STH/175

Summary
Brief summary
Dairy intolerance is often attributed to lactose intolerance but there may be individuals who exhibit an intolerance due to the A1 version of bovine beta-casein protein found in the dairy supply. The peptide sequence variation in the A2 version of beta-casein may alter the digestion but it is still unclear how these variants of the bovine beta-casein in milk are digested and metabolised in humans. This study aims to evaluate digestive, metabolic and immunological responses to milks with or without lactose and A1 beta–casein in self-reported dairy intolerant individuals.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69762 0
Prof David Cameron-Smith
Address 69762 0
The Liggins Institute
University of Auckland
Building 505
Grafton, Auckland
1023
Country 69762 0
New Zealand
Phone 69762 0
+6499231336
Fax 69762 0
+649 3738763
Email 69762 0
d.cameron-smith@auckland.ac.nz
Contact person for public queries
Name 69763 0
Prof David Cameron-Smith
Address 69763 0
The Liggins Institute
University of Auckland
Building 505
Grafton, Auckland
1023
Country 69763 0
New Zealand
Phone 69763 0
+6499231336
Fax 69763 0
+649 3738763
Email 69763 0
d.cameron-smith@auckland.ac.nz
Contact person for scientific queries
Name 69764 0
Prof David Cameron-Smith
Address 69764 0
The Liggins Institute
University of Auckland
Building 505
Grafton, Auckland, 1023
New Zealand
Country 69764 0
New Zealand
Phone 69764 0
+6499231336
Fax 69764 0
+649 3738763
Email 69764 0
d.cameron-smith@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary