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Effects of A2 Milk on Gastrointestinal Function in Non-lactose Milk Intolerance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03060395
Recruitment Status : Completed
First Posted : February 23, 2017
Last Update Posted : April 28, 2020
Sponsor:
Information provided by (Responsible Party):
Sandrine Claus, University of Reading

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Milk Intolerance Dietary Supplement: A2 milk 100 Dietary Supplement: A2 milk 150 Dietary Supplement: A2 milk 200 Dietary Supplement: A2 milk 250 Dietary Supplement: A1/A2 milk 100 Dietary Supplement: A1/A2 milk 150 Dietary Supplement: A1/A2 milk 200 Dietary Supplement: A1/A2 milk 250 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of A2 Milk on Gastrointestinal Function of Volunteers Affected by Non-lactose Milk Intolerance
Actual Study Start Date : April 1, 2017
Actual Primary Completion Date : April 30, 2018
Actual Study Completion Date : March 31, 2019

Resource links provided by the National Library of Medicine


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 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




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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)

  4. 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

  5. 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

  6. 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

  7. Height (in m) used to detect change in BMI (kg/m^2) [ Time Frame: baseline ]
  8. Weight (in kg) used to detect change in BMI (kg/m^2) [ Time Frame: baseline, 14 days, 28 days, 42 days and 56 days ]
  9. Change in systolic blood pressure in mmHg [ Time Frame: baseline, 14 days, 28 days, 42 days and 56 days ]
  10. Change in diastolic blood pressure in mmHg [ Time Frame: baseline, 14 days, 28 days, 42 days and 56 days ]
  11. 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 ]
  12. 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 ]
  13. Self-reported change in gut transit time [ Time Frame: 14 days, 42 days and 56 days ]
  14. Monitoring of changes in psychological behaviour assessed by TMT [ Time Frame: baseline, 14 days, 28 days, 42 days and 56 days ]
  15. Monitoring of changes in psychological behaviour assessed by Letter Memory Test [ Time Frame: baseline, 14 days, 28 days, 42 days and 56 days ]
  16. Monitoring of changes in psychological behaviour assessed by Flanger Test [ Time Frame: baseline, 14 days, 28 days, 42 days and 56 days ]
  17. Monitoring of changes in mood measured by PANAS questionnaire [ Time Frame: baseline, 14 days, 28 days, 42 days and 56 days ]
  18. Change in stool consistency using the Bristol stool chart [ Time Frame: baseline, 14 days, 28 days, 42 days and 56 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 56 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03060395


Locations
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United Kingdom
Department of Food and Nutritional Sciences
Reading, Berkshire, United Kingdom, RG6 6AP
Sponsors and Collaborators
University of Reading
Investigators
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Principal Investigator: Sandrine P Claus, PhD University of Reading
Publications:
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Responsible Party: Sandrine Claus, Associate Professor in Integrative Metabolism, University of Reading
ClinicalTrials.gov Identifier: NCT03060395    
Other Study ID Numbers: A2study
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: April 28, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lactose Intolerance
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases