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Effects Comparison of A1 and A2 Milk on Gastrointestinal Physiology, Symptoms and Cognitive Behavior

Primary Purpose

Lactose Intolerance

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Oral consumption milk Tetra Pak
Sponsored by
a2 Milk Company Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Lactose Intolerance

Eligibility Criteria

25 Years - 68 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • 25~3568 years old male or female subjects who:
  • Non-regular milk drinker with self-reported intolerance to commercial milk;
  • Suffered from mild to moderate digestive discomfort after milk consumption;
  • Have normal electrocardiograms (ECG) and blood pressure during quiet respiration;
  • Agree not to take any medication, supplements, nutrition or 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 enroll 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:

  • Female on pregnant or feeding;
  • Have known dairy allergy;
  • Have severe response to milk intolerance;
  • Have history of faecal impaction;
  • 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;
  • 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 and cardiovascular diseases;
  • Current or previous alcohol abuser, currently taking or took illicit drugs, substance or OTC prescription drugs in regular frequency which may affect gastrointestinal disorders and study result;
  • Currently suffering from any gastrointestinal disorders or gastrointestinal disease, including but not limited to: 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Sequence A1-A2

    Sequence A2-A1

    Arm Description

    Oral consumption of milk containing both A1 and A2 type beta casein in intervention phase 1 and milk containing only A2 type beta casein in intervention phase 2.

    Oral consumption of milk containing only A2 type beta casein in intervention phase 1 and milk containing both A1 and A2 type beta casein in intervention phase 2.

    Outcomes

    Primary Outcome Measures

    Serum levels of immune response markers in correlation to symptoms of intolerance
    Serum levels of interlukin-4, IgE, IgG1 and IgG2A

    Secondary Outcome Measures

    Regional gut transit time
    Measurement using "Smart Pill" device
    Fecal short chain fatty acid measurements
    Markers for absorption of nutrients and gut inflammation
    Gastrointestinal symptoms (VAS score)
    Evaluated through VAS score reporting
    Stool frequency
    Stool consistency (Bristol Score)
    Measured via Bristol Score
    Response time and error rate
    Markers for change of cognition function evaluated via Subtle Cognitive Impairment Test (SCIT)

    Full Information

    First Posted
    March 30, 2015
    Last Updated
    April 1, 2015
    Sponsor
    a2 Milk Company Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02406469
    Brief Title
    Effects Comparison of A1 and A2 Milk on Gastrointestinal Physiology, Symptoms and Cognitive Behavior
    Official Title
    Comparative Effects of Milk With A2 Type Beta Casein Versus Milk With A1 and A2 Beta Casein Proteins on Gastrointestinal Physiology, Symptoms and Cognitive Behavior for the Health People Who Are Intolerant to Traditional Cow Milk
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    October 2014 (undefined)
    Primary Completion Date
    December 2014 (Actual)
    Study Completion Date
    February 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    a2 Milk Company Ltd.

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a single-site, double-blinded, randomized, controlled, 2X2 cross-over study aiming to compare effects of milk containing only A2 type beta casein versus milk containing both A1 and A2 beta casein proteins on the gastrointestinal physiology, symptoms and cognitive behaviour for the health people who are intolerant to traditional cow's milk.
    Detailed Description
    This is a single-site, double-blinded, randomized, controlled, cross-over study in healthy milk drinkers of 4 weeks' consumption with milk containing only A2 type beta casein (called A2 milk) versus milk containing both A1 and A2 beta casein proteins (called A1 milk) to compare the effects on gut inflammation (CRP, HB, IL-4, IgG, IgE, IgG1, IgG2a), gastrointestinal symptoms (via VAS score including Bloating, Abdominal pain, Flatulence, Break wind, Borborygmi), regional gut transit times (via 'Smart Pill') and behavioral well-being (CNAQ), and stool habits. The cross-over study will take 2 phases (2 weeks in each phase) of product intervention, 2 weeks of wash-out before each intervention phase and then followed by 5 wks of statistical analysis and clinical report completed. According to ICH-GCP Guidelines and Chinese regulations issued by SFDA, all subjects will be informed of study procedures and sign the informed consent before enrollment. At screening phase, subjects will be informed about study requirements, procedures, potential risks and benefits of participation. Subjects will not be enrolled into the study until ICF is well informed and accepted. At the Screening phase, 100 subjects had the Urine galactose (U-gal) test to screen 45 subjects eligible for the study and they should simultaneously meet the Inclusion and Exclusion criteria. Subjects should be fasting on the morning of testing, and then drink 300 ml full-fat milk within 3-5 minutes. Empty the urine 1 hour after drinking, and collect midstream urine 2 hours after milk-consumption for urinary galactose test with symptom scores recorded accordingly. Urine galactose (U-gal) tests positive indicating the lactase deficiency, if it is accompanied by abdominal distension, abdominal pain and other symptoms of more than 1 item; it is identified as lactose intolerance. 100 subjects took part in the screening by U-gal test and forty-five (45) qualified subjects (stratified by male to female approximate ratio 1:1) will be enrolled into the study with assumed 11.1% attrition rate to keep 20 subjects per group to complete the cross-over study. Subjects will be enrolled in the study site authorized by Xin Hua Hospital during the screening phase. Sun Jianqin, Professor, leading PI, is responsible for the academic guidance to define all qualified subjects. The study will be conducted by the team of PIs and monitored by SPRIM CHINA in accordance with Chinese Good Clinical Practices (CGCP's). Subjects will sign the informed consent form before study intervention. Eligible subjects will be randomized into 2 groups, and one of two possible products sequences will be assigned, A1 milk or A2 milk. Subjects completed 2 weeks A1 or A2 intervention after initial 2 weeks of washout, and then cross over to the opposite intervention for 2 weeks after second 2 weeks of washout. The efficacy of the study products was evaluated by biomarkers in the blood or feces and linked questionnaires at the duration of the cross-over study. During the study intervention, subjects need to visit the site every week; follow-up telephone will be made at the duration of wash-out phase and the related information will be collected by CRAs accordingly.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Lactose Intolerance

    7. Study Design

    Primary Purpose
    Basic Science
    Study Phase
    Phase 4
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    45 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Sequence A1-A2
    Arm Type
    Experimental
    Arm Description
    Oral consumption of milk containing both A1 and A2 type beta casein in intervention phase 1 and milk containing only A2 type beta casein in intervention phase 2.
    Arm Title
    Sequence A2-A1
    Arm Type
    Placebo Comparator
    Arm Description
    Oral consumption of milk containing only A2 type beta casein in intervention phase 1 and milk containing both A1 and A2 type beta casein in intervention phase 2.
    Intervention Type
    Dietary Supplement
    Intervention Name(s)
    Oral consumption milk Tetra Pak
    Intervention Description
    Oral consumption of assigned products in the form of Tetra Pak (A1 or A2 milk according to randomization), 250 ml/time, 2 times daily after meal, for a total of 28 days (14 days in each intervention phase).
    Primary Outcome Measure Information:
    Title
    Serum levels of immune response markers in correlation to symptoms of intolerance
    Description
    Serum levels of interlukin-4, IgE, IgG1 and IgG2A
    Time Frame
    Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)
    Secondary Outcome Measure Information:
    Title
    Regional gut transit time
    Description
    Measurement using "Smart Pill" device
    Time Frame
    End of intervention phase 1 (Day 14), end of intervention phase 2 (Day 42)
    Title
    Fecal short chain fatty acid measurements
    Description
    Markers for absorption of nutrients and gut inflammation
    Time Frame
    Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)
    Title
    Gastrointestinal symptoms (VAS score)
    Description
    Evaluated through VAS score reporting
    Time Frame
    Daily from Day 0 to Day 42
    Title
    Stool frequency
    Time Frame
    Daily from Day 0 to Day 42
    Title
    Stool consistency (Bristol Score)
    Description
    Measured via Bristol Score
    Time Frame
    Daily from Day 0 to Day 42
    Title
    Response time and error rate
    Description
    Markers for change of cognition function evaluated via Subtle Cognitive Impairment Test (SCIT)
    Time Frame
    Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    25 Years
    Maximum Age & Unit of Time
    68 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: 25~3568 years old male or female subjects who: Non-regular milk drinker with self-reported intolerance to commercial milk; Suffered from mild to moderate digestive discomfort after milk consumption; Have normal electrocardiograms (ECG) and blood pressure during quiet respiration; Agree not to take any medication, supplements, nutrition or 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 enroll 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: Female on pregnant or feeding; Have known dairy allergy; Have severe response to milk intolerance; Have history of faecal impaction; 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; 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 and cardiovascular diseases; Current or previous alcohol abuser, currently taking or took illicit drugs, substance or OTC prescription drugs in regular frequency which may affect gastrointestinal disorders and study result; Currently suffering from any gastrointestinal disorders or gastrointestinal disease, including but not limited to: 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.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Andrew J Clarke, PhD
    Organizational Affiliation
    a2 Milk Company Ltd.
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    27680716
    Citation
    Deth R, Clarke A, Ni J, Trivedi M. Clinical evaluation of glutathione concentrations after consumption of milk containing different subtypes of beta-casein: results from a randomized, cross-over clinical trial. Nutr J. 2016 Sep 29;15(1):82. doi: 10.1186/s12937-016-0201-x.
    Results Reference
    derived
    PubMed Identifier
    27039383
    Citation
    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.
    Results Reference
    derived

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    Effects Comparison of A1 and A2 Milk on Gastrointestinal Physiology, Symptoms and Cognitive Behavior

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