- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03060395
Effects of A2 Milk on Gastrointestinal Function in Non-lactose Milk Intolerance
April 27, 2020 updated by: Sandrine Claus, University of Reading
Effects of A2 Milk on Gastrointestinal Function of Volunteers Affected by Non-lactose Milk Intolerance
There is increasing evidence that a number of people experience moderate milk intolerance characterised by increased gas production, bloating and abdominal cramp, which can neither be attributed to lactose intolerance, nor to milk protein allergy.
Milk digestion can lead to the formation of bioactive peptides, one of which derived from a mutated gene variant (A1) coding for milk beta-casein has been associated with increased gastrointestinal inflammation and poor gastrointestinal function.
In this study, we hypothesise that consumption of non-mutated A2 milk will improve gastrointestinal symptoms in non-lactose milk intolerant individuals.
Study Overview
Status
Completed
Conditions
Detailed Description
Non-lactose milk intolerance is a condition that has not been defined clinically yet but the current literature reports existence of subjects who are moderately milk intolerant and whose intolerance can neither be attributed to a defect in lactose intolerance, nor to milk protein allergy.
Yet, they experience at least one or two of the following symptoms following milk consumption: gases, bloating, abdominal cramp.
It is known that the A1gene variant coding for beta-casein leads to the production of a bioactive peptide with opioid activity named betacasomorphin 7 (BCM7).
This peptide has been associated with several metabolic health disorders including diabetes, elevated cardiovascular risk and stimulation of pro-inflammatory signals.
Recently, it was reported that non-lactose milk intolerant subjects did not experience such symptoms when consuming milk containing the non-mutated A2 gene variant coding for beta-casein.
In this study, we hypothesise that consumption of A2 milk will improve gastrointestinal symptoms in non-lactose milk intolerant individuals.
The primary outcome of this study will be the reduction of gastrointestinal inflammation following a course of A2 milk consumption.
Study Type
Interventional
Enrollment (Actual)
37
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Berkshire
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Reading, Berkshire, United Kingdom, RG6 6AP
- Department of Food and Nutritional Sciences
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 56 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- BMI: 20-35kg/m2
- Glucose<7mmol/l (not diagnosed with diabetes)
- Total cholesterol<7mmol/l
- Triacylglycerol<4mmol/l
- Normal liver and kidney function
- Regular milk drinker with self-reported intolerance to commercial milk.
- Suffered from mild to moderate digestive discomfort after milk consumption.
- Have normal blood pressure 120/80 mmHg (BP <160/90 mmHg can be accepted) during quiet respiration.
- Agree not to take any medication, supplements and other dairy products including acidophilus milk
- Be willing to comply with all the requirements and procedures of the study.
- Agree to sign the informed consent form;
- Agree not to enrol in another interventional clinical research study while participating in this study.
- Fully understand the nature, objective, benefit and the potential risks and side effects of the study.
Exclusion Criteria:
- Females who are pregnant or planning to be a pregnant and lactating.
- Have known dairy allergy.
- Have stopped drinking milk for the last 6 month.
- Have history of lactose intolerance
- Have history of faecal impaction.
- Received antibiotics in the previous six months
- Smoker
- Anemia
- Trying to lose weight by following a diet or exercise regimen designed for weight loss, or taking any drug influencing appetite and any drug for weight loss for the last three months.
- Have participated in similar dairy or probiotics-containing product's clinical trials within 3 months before the screening.
- Currently taking medicines for cardiovascular or metabolic disease.
- History of alcohol or drug misuse.
- Have history of or be diagnosed of any of the following diseases that may affect the study results: gastrointestinal disorders, hepatopathy, nephropathy, endocrine disease, blood disorders, respiratory, cardiovascular diseases and known on-going allergy such as asthma.
- Currently suffering from any gastrointestinal disorders or gastrointestinal disease, including irritable bowel syndrome, colitis, ulcerative colitis, celiac disease, irritable bowel syndrome (IBS);
- Had hospitalizations within 3 months before screening; Currently drug frequency user of that may affect the gastrointestinal function or immune system. As judged by investigator.
- Who take medication at least the last 6-month.
- Who do excessive exercise not as part of a weight-loss regime, e.g. athletes.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Sham Comparator: A1/A2 milk
Commercial conventional A1/A2 semi-skimmed fresh pasteurised cow milk. Progressive intake of intervention milk as follows:
|
Days 1 and 2: 100 mL A1/A2 milk twice a day
Days 3 and 4: 150 mL A1/A2 milk twice a day
Days 5 and 6: 200 mL A1/A2 milk twice a day
Days 7 to14: 250 mL A1/A2 milk twice a day
|
Active Comparator: A2 milk
Commercial A2 semi-skimmed fresh pasteurised cow milk. Progressive intake of intervention milk as follows:
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Days 1 and 2: 100 mL A2 milk twice a day
Days 3 and 4: 150 mL A2 milk twice a day
Days 5 and 6: 200 mL A2 milk twice a day
Days 7 to 14: 250 mL A2 milk twice a day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in gastrointestinal inflammation indicated by fecal calprotectin
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
Measurement of fecal calprotectin (ug/g feces)
|
baseline, 14 days, 28 days, 42 days and 56 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in NMR-based urinary metabolic profiles
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
Measured using High Resolution 700MHz proton NMR spectroscopy (Bruker) (no unit)
|
baseline, 14 days, 28 days, 42 days and 56 days
|
Change in NMR-based plasma metabolic profiles
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
Measured using High Resolution 700MHz proton NMR spectroscopy (Bruker) (no unit)
|
baseline, 14 days, 28 days, 42 days and 56 days
|
Change in NMR-based fecal metabolic profiles
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
Measured using High Resolution 700MHz proton NMR spectroscopy (Bruker) (no unit)
|
baseline, 14 days, 28 days, 42 days and 56 days
|
Change in gut microbiota ecosystem assessed by sequencing the 16S rDNA extracted from feces
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
Measures relative abundance of bacterial taxa
|
baseline, 14 days, 28 days, 42 days and 56 days
|
Change in systemic inflammation indicated by circulating levels of high sensitivity C-reactive protein
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
hs-CRP in mg/L
|
baseline, 14 days, 28 days, 42 days and 56 days
|
Change in gastrointestinal function assessed using visual analogue scale for GI symptoms
Time Frame: 14 days
|
Measures gases, bloating, abdominal cramps, diarrhoea, headache, constipation, nausea and rash
|
14 days
|
Height (in m) used to detect change in BMI (kg/m^2)
Time Frame: baseline
|
baseline
|
|
Weight (in kg) used to detect change in BMI (kg/m^2)
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
baseline, 14 days, 28 days, 42 days and 56 days
|
|
Change in systolic blood pressure in mmHg
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
baseline, 14 days, 28 days, 42 days and 56 days
|
|
Change in diastolic blood pressure in mmHg
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
baseline, 14 days, 28 days, 42 days and 56 days
|
|
Diagnostic of lactose intolerance by breath hydrogen concentration following ingestion of 25g lactose in 250 mL water
Time Frame: screening visit, 14 days, 42 days and 56 days
|
screening visit, 14 days, 42 days and 56 days
|
|
Diagnostic of lactose intolerance by breath methane concentration following ingestion of 25g lactose in 250 mL water
Time Frame: screening visit, 14 days, 42 days and 56 days
|
screening visit, 14 days, 42 days and 56 days
|
|
Self-reported change in gut transit time
Time Frame: 14 days, 42 days and 56 days
|
14 days, 42 days and 56 days
|
|
Monitoring of changes in psychological behaviour assessed by TMT
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
baseline, 14 days, 28 days, 42 days and 56 days
|
|
Monitoring of changes in psychological behaviour assessed by Letter Memory Test
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
baseline, 14 days, 28 days, 42 days and 56 days
|
|
Monitoring of changes in psychological behaviour assessed by Flanger Test
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
baseline, 14 days, 28 days, 42 days and 56 days
|
|
Monitoring of changes in mood measured by PANAS questionnaire
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
baseline, 14 days, 28 days, 42 days and 56 days
|
|
Change in stool consistency using the Bristol stool chart
Time Frame: baseline, 14 days, 28 days, 42 days and 56 days
|
baseline, 14 days, 28 days, 42 days and 56 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Sandrine P Claus, PhD, University of Reading
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Ho S, Woodford K, Kukuljan S, Pal S. Comparative effects of A1 versus A2 beta-casein on gastrointestinal measures: a blinded randomised cross-over pilot study. Eur J Clin Nutr. 2014 Sep;68(9):994-1000. doi: 10.1038/ejcn.2014.127. Epub 2014 Jul 2.
- Johnson AO, Semenya JG, Buchowski MS, Enwonwu CO, Scrimshaw NS. Correlation of lactose maldigestion, lactose intolerance, and milk intolerance. Am J Clin Nutr. 1993 Mar;57(3):399-401. doi: 10.1093/ajcn/57.3.399.
- Ul Haq MR, Kapila R, Sharma R, Saliganti V, Kapila S. Comparative evaluation of cow beta-casein variants (A1/A2) consumption on Th2-mediated inflammatory response in mouse gut. Eur J Nutr. 2014 Jun;53(4):1039-49. doi: 10.1007/s00394-013-0606-7. Epub 2013 Oct 29.
- Jianqin S, Leiming X, Lu X, Yelland GW, Ni J, Clarke AJ. Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk. Nutr J. 2016 Apr 2;15:35. doi: 10.1186/s12937-016-0147-z. Erratum In: Nutr J. 2016;15(1):45.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2017
Primary Completion (Actual)
April 30, 2018
Study Completion (Actual)
March 31, 2019
Study Registration Dates
First Submitted
January 17, 2017
First Submitted That Met QC Criteria
February 17, 2017
First Posted (Actual)
February 23, 2017
Study Record Updates
Last Update Posted (Actual)
April 28, 2020
Last Update Submitted That Met QC Criteria
April 27, 2020
Last Verified
April 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- A2study
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
IPD Plan Description
We do not plan to share IPD with other researchers outside the University of Reading.
Anonymous data may be made available upon publication of the study outcome in appropriate repositories (e.g.
metabolomic profiles).
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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