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Trial registered on ANZCTR


Registration number
ACTRN12617001518358
Ethics application status
Approved
Date submitted
17/10/2017
Date registered
31/10/2017
Date last updated
13/11/2019
Date data sharing statement initially provided
13/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Los aMiGoS: Is LactOSe tolerance impacted by repeated exposure to A2 beta-casein MIlk, with effects on Gut COmfort Symptoms
Scientific title
In young lactose intolerant adults, does the prolonged consumption of A1 beta-casein free milk products improve lactose absorption and tolerance by reduced gastrointestinal inflammation compared to conventional A1 and A2 beta-casein containing milk products
Secondary ID [1] 292979 0
Nil
Universal Trial Number (UTN)
U1111­-1201-­8956
Trial acronym
Los aMiGos
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Impaired digestion 304882 0
Lactose intolerance 305148 0
Condition category
Condition code
Diet and Nutrition 304193 304193 0 0
Other diet and nutrition disorders
Inflammatory and Immune System 304472 304472 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects randomized to the intervention will be assigned, in a cross-over manner, to 2 weeks daily consumption of either conventional milk products or a2 milk products (500 ml of full fat milk + 80 g hard cheese), each preceded by 2 weeks of dairy avoidance. Participants need to avoid any other dairy products than provided and fill in the food questionnaires (checklist) throughout the intervention period.
Intervention code [1] 299218 0
Lifestyle
Comparator / control treatment
Conventional milk which contains both a1 and a2 beta-casein protein.
Control group
Active

Outcomes
Primary outcome [1] 303501 0
Mean change in breath hydrogen between the two intervention arms.
Timepoint [1] 303501 0
Pre lactose ingestion (fasting) and every 30 min post lactose ingestion for 5 hours before (baseline) and after the 2 weeks intervention.
Secondary outcome [1] 339084 0
Analysis of digestive symptoms scores e.g. bloating, nausea, vomiting, diarrhea, gastric reflux and abdominal pain by 10 cm Visual Analog Scale (VAS) to measure the change in digestive symptoms before and after the 2 weeks of intervention.
Timepoint [1] 339084 0
Pre lactose ingestion (fasting) and every 30 min post lactose ingestion for 5 hours before and after the 2 weeks intervention.
Secondary outcome [2] 339085 0
Comparison of gut inflammation between the two milk products as measured by fecal markers. This includes measuring fecal calprotectin using ELISA and stool cellular indices (protein and gene expression in intestinal cells).
Timepoint [2] 339085 0
Baseline and 2 weeks post intervention (fasting).
Secondary outcome [3] 339086 0
Non targeted analysis of fecal metabolites between the two intervention arms by using non-targeted GC-MS .
Timepoint [3] 339086 0
Baseline and 2 weeks post intervention (fasting).
Secondary outcome [4] 339098 0
Changes in systemic inflammatory response between the two intervention arms. This include circulating protein cytokines (IL-6, CRP, TNF-a) and immunoglobulin (IgG, IgA and IGM) in serum and PBMCs using ELISA.
Timepoint [4] 339098 0
Baseline and two weeks post intervention (fasting).
Secondary outcome [5] 339099 0
Differences in plasma glucose level using a Roche Cobas c311 autoanalyser by enzymatic colorimetric assay.
Timepoint [5] 339099 0
Pre lactose ingestion (fasting) and every 30 minutes post lactose ingestion for first hour then hourly for 5 hours before and after the two weeks intervention.
Secondary outcome [6] 339100 0
Differences in plasma amino acid profiles between the two intervention arms using UPLC.
Timepoint [6] 339100 0
Baseline and two weeks post intervention (fasting).
Secondary outcome [7] 339101 0
Analysis of the gastrointestinal symptoms assessed during the intervention measured by
Daily Live Gastrointestinal Symptom diary (LGS).
Timepoint [7] 339101 0
Daily for 3 days at baseline, and start and end of intervention arm.
Secondary outcome [8] 339103 0
Measure the change in serum peptides between the two intervention arms. This will include targeted analyses of beta-casomorphin-7 using LC-MS and non-targeted analyses of peptides using untargeted LCMS approach.
Timepoint [8] 339103 0
Baseline and two weeks post intervention (fasting).
Secondary outcome [9] 339919 0
Analyse the changes in fecal microbiome between the two intervention arms.
Timepoint [9] 339919 0
Baseline and 2 weeks post intervention (fasting)
Secondary outcome [10] 339920 0
Analyse the change in miRNA between the two intervention arms.
Timepoint [10] 339920 0
Baseline and 2 weeks post intervention (fasting).
Secondary outcome [11] 340032 0
Analyse the intestinal inflammation using MRI by measuring the intestinal wall thickness. between the two intervention arms.
Timepoint [11] 340032 0
Baseline and 2 weeks post intervention (fasting).
Secondary outcome [12] 340035 0
Analyse the bowel motions between the two interventions as measured by Bristol Stool Scale.
Timepoint [12] 340035 0
Daily for 3 days at baseline, and start and end of intervention arm.
Secondary outcome [13] 340036 0
Analyse the digestive symptoms e.g bloating, nausea, vomiting, diarrhea, gastric reflux and abdominal pain before and after the two weeks intervention by using 10 cm Visual Analog Scale (VAS) during the intervention.
Timepoint [13] 340036 0
Daily for 3 days at baseline, and start and end of intervention arm.
Secondary outcome [14] 340060 0
Analyse the change in oxidative stress markers between the two intervention groups including glutathione (GSH), superoxide dismutase (SOD) using enzyme immunoassays from plasma.
Timepoint [14] 340060 0
Baseline and 2 weeks post intervention (fasting).

Eligibility
Key inclusion criteria
20-40 years
BMI 18-28 kg/m2
Self-described lactose intolerant
Lactose intolerant (confirmed by lactose tolerance test: breath hydrogen and symptoms)
No history of gastrointestinal disease or metabolic disease.
Minimum age
20 Years
Maximum age
40 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Are not lactose intolerant.
Have an allergy to milk.
Are diagnosed with gastrointestinal disease (i.e. celiac, Crohn’s, colitis, etc.) or pre-existing metabolic disease.
Are currently taking medications expected to interfere with normal digestive or metabolic processes including proton pump inhibitors, laxatives, antibiotics etc.
Have a 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 randomization and allocation is performed by third party who is not involved in the study procedures or analyses 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
Factorial ANOVA will be used to determine differences in the primary and secondary continuous endpoints. Secondary outcomes will be analysed by ANOVA, generalised estimating equations and regression models as appropriate.
Using a clinically relevant reduction in breath hydrogen of 50%, and based on data obtained from graded lactose challenges (12.5g versus 25g) to detect a difference of 99ppm/h to 54ppm/h with a standard deviation of 41 would require 18 subjects per group (sex) to achieve a 90% power with alpha set at 0.05.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/10/2017
Actual
1/11/2017
Date of last participant enrolment
Anticipated
1/05/2018
Actual
12/11/2018
Date of last data collection
Anticipated
Actual
13/12/2018
Sample size
Target
40
Accrual to date
Final
40
Recruitment outside Australia
Country [1] 9243 0
New Zealand
State/province [1] 9243 0
Auckland

Funding & Sponsors
Funding source category [1] 297604 0
Commercial sector/Industry
Name [1] 297604 0
AgResearch Ltd.
Country [1] 297604 0
New Zealand
Funding source category [2] 297608 0
Commercial sector/Industry
Name [2] 297608 0
The a2 Milk Company Limited
Country [2] 297608 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] 296618 0
Commercial sector/Industry
Name [1] 296618 0
The a2 Milk Company Limited
Address [1] 296618 0
Shortland Street
Auckland
1010
New Zealand
Country [1] 296618 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298697 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 298697 0
Ethics committee country [1] 298697 0
New Zealand
Date submitted for ethics approval [1] 298697 0
20/09/2017
Approval date [1] 298697 0
25/10/2017
Ethics approval number [1] 298697 0
17/CEN/198

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77926 0
Prof David Cameron-Smith
Address 77926 0
The Liggins Institute
University of Auckland
Building 505
Grafton, Auckland
1023
Country 77926 0
New Zealand
Phone 77926 0
+6499231336
Fax 77926 0
+649 3738763
Email 77926 0
d.cameron-smith@auckland.ac.nz
Contact person for public queries
Name 77927 0
David Cameron-Smith
Address 77927 0
The Liggins Institute
University of Auckland
Building 505
Grafton, Auckland
1023
Country 77927 0
New Zealand
Phone 77927 0
+6499231336
Fax 77927 0
+649 3738763
Email 77927 0
d.cameron-smith@auckland.ac.nz
Contact person for scientific queries
Name 77928 0
David Cameron-Smith
Address 77928 0
The Liggins Institute
University of Auckland
Building 505
Grafton, Auckland
1023
Country 77928 0
New Zealand
Phone 77928 0
+6499231336
Fax 77928 0
+649 3738763
Email 77928 0
d.cameron-smith@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.