Lactose IntolerancePhase 4NCT02406469
Effects Comparison of A1 and A2 Milk on Gastrointestinal Physiology, Symptoms and Cognitive Behavior
A Phase 4 study testing Oral consumption milk Tetra Pak in people with Lactose Intolerance, run by a2 Milk Company Ltd..
Trial 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… Read more about this study
- Who is it for?
- Ages 25 to 68 yearsHealthy volunteers can take part
- Conditions the study is for
- Lactose Intolerance
- What is being tested?
- Oral consumption milk Tetra Pak
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- No sites listed yet
- Study dates
- Oct 2014to Feb 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 68 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.
About this study
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
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.
Read the 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.
- Conditions
- Lactose Intolerance
- Being tested
- Oral consumption milk Tetra Pak
- Medical subject headings
- Lactose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral consumption milk Tetra PakDietary supplement
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).
| Study group | Role | What they receive |
|---|---|---|
| Sequence A1-A2 | Experimental | 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. Receives: Dietary Supplement: Oral consumption milk Tetra Pak |
| Sequence A2-A1 | Placebo comparator | 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. Receives: Dietary Supplement: Oral consumption milk Tetra Pak |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum levels of immune response markers in correlation to symptoms of intolerance
Serum levels of interlukin-4, IgE, IgG1 and IgG2A
Measured: Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)
Secondary outcomes (6)
Regional gut transit time
Measurement using "Smart Pill" device
Measured: End of intervention phase 1 (Day 14), end of intervention phase 2 (Day 42)
Fecal short chain fatty acid measurements
Markers for absorption of nutrients and gut inflammation
Measured: Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)
Gastrointestinal symptoms (VAS score)
Evaluated through VAS score reporting
Measured: Daily from Day 0 to Day 42
Stool frequency
Measured: Daily from Day 0 to Day 42
Stool consistency (Bristol Score)
Measured via Bristol Score
Measured: Daily from Day 0 to Day 42
Response time and error rate
Markers for change of cognition function evaluated via Subtle Cognitive Impairment Test (SCIT)
Measured: Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2015 (estimated)
- Study startOct 2014
- Primary completionDec 2014
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lactose IntoleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- a2 Milk Company Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andrew J Clarke, PhD, Study director, a2 Milk Company Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02406469
- Sponsor's protocol ID
- 14-SC-07-A2-01
- Status last verified
- Mar 2015
- First submitted
- 30 Mar 2015
- Last updated
- 2 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 27680716Jianqin 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.
PubMed 27039383
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02406469
- Acronym / sponsor ID
- 14-SC-07-A2-01
- Conditions
- Lactose Intolerance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- a2 Milk Company Ltd.Industry (pharma, biotech, devices)
- Study start
- Oct 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 2 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence A1-A2 | Experimental | Dietary Supplement: Oral consumption milk Tetra PakOral 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. |
| Sequence A2-A1 | Placebo comparator | Dietary Supplement: Oral consumption milk Tetra PakOral 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. |
Who may qualify
- Ages
- 25 to 68 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (12 listed)
- 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 ;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral consumption milk Tetra PakOral 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). | Dietary supplement | Sequence A1-A2, Sequence A2-A1 |
Primary outcome
Serum levels of immune response markers in correlation to symptoms of intolerance
Time frame: Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)
Serum levels of interlukin-4, IgE, IgG1 and IgG2A
6 secondary outcomes
Regional gut transit time
Time frame: End of intervention phase 1 (Day 14), end of intervention phase 2 (Day 42)
Fecal short chain fatty acid measurements
Time frame: Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)
Gastrointestinal symptoms (VAS score)
Time frame: Daily from Day 0 to Day 42
Stool frequency
Time frame: Daily from Day 0 to Day 42
Stool consistency (Bristol Score)
Time frame: Daily from Day 0 to Day 42
Response time and error rate
Time frame: Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2015.
- Derived from this study: PubMed 27680716Deth 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.
- Derived from this study: PubMed 27039383Jianqin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew J Clarke, PhD study director
a2 Milk Company Ltd.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oral consumption milk Tetra Pak in people with Lactose Intolerance, run by a2 Milk Company Ltd..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum levels of immune response markers in correlation to symptoms of intolerance (time frame: Baseline 1 (Day 0), end of intervention phase 1 (Day 14), baseline 2 (Day 28), end of intervention phase 2 (Day 42)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02406469, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2015.