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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
37

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United Kingdom
    • Berkshire
      • Reading, Berkshire, United Kingdom, RG6 6AP
        • Department of Food and Nutritional Sciences

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 twice a day
  • Days 3 and 4: 150 mL twice a day
  • Days 5 and 6: 200 mL twice a day
  • Days 7 to 14: 250 mL twice a day
Dietary supplement: A1/A2 milk 100
Days 1 and 2: 100 mL A1/A2 milk twice a day
Dietary supplement: A1/A2 milk 150
Days 3 and 4: 150 mL A1/A2 milk twice a day
Dietary supplement: A1/A2 milk 200
Days 5 and 6: 200 mL A1/A2 milk twice a day
Dietary supplement: A1/A2 milk 250
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:

  • Days 1 and 2: 100 mL twice a day
  • Days 3 and 4: 150 mL twice a day
  • Days 5 and 6: 200 mL twice a day
  • Days 7 to 14: 250 mL twice a day
Dietary supplement: A2 milk 100
Days 1 and 2: 100 mL A2 milk twice a day
Dietary supplement: A2 milk 150
Days 3 and 4: 150 mL A2 milk twice a day
Dietary supplement: A2 milk 200
Days 5 and 6: 200 mL A2 milk twice a day
Dietary supplement: A2 milk 250
Days 7 to 14: 250 mL A2 milk twice a day

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Reading

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 17, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 17, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 23, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 28, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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