Gut InflammationPhase 4NCT03081845

A1 Versus A2® Milk on the Gastrointestinal Physiology, Symptoms and Cognitive Behaviour for the Preschool Children

A Phase 4 study testing Oral consumption of milk A1 in study phase 1, Oral consumption of milk A2 in study phase 1 and Oral consumption of milk A1 in study phase 2 in people with Gut Inflammation, run by a2 Milk Company Ltd..

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a multiple-sites, double-blinded, randomized, controlled, parallel-designed, cross-over study among healthy preschoolers with 5 days consumption of A2 or A1 milk to compare the effects on gut inflammation, gastrointestinal symptoms and behavioral well-being. Read more about this study

Who is it for?: Ages 5 to 6 yearsHealthy volunteers can take part
Conditions the study is for: Gut Inflammation
What is being tested?: Oral consumption of milk A1 in study phase 1, Oral consumption of milk A2 in study phase 1 and Oral consumption of milk A1 in study phase 2
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: No sites listed yet
Study dates: 13 Sep 2016to 20 Jan 2017
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 5 to 6 years
All sexes
Healthy volunteers accepted
Child

Who may be able to join

Non-regular milk drinker;
Suffered from mild to moderate milk intolerance;
Agree not to take any medication, supplements, nutrition or other dairy products including acidophilus milk;
Parent(s) or legal guardian's consent to the study and willing to comply with study procedures;
Parent(s) or guardian of infant agrees not to enroll infant another clinical 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

Have known dairy allergy;
Suffered from severe milk intolerance;
Unable to give written informed consent;
Use of antibiotics at the time of screening, or during the past two weeks;
Have history of fecal 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;

Show all 12Show fewer

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;
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;
According to investigator's judgment, current frequent users of drugs may affect the gastrointestinal function or immune system.

About this study

Official title: Comparative Effects of A1 Versus A2® Milk on the Gastrointestinal Physiology, Symptoms and Cognitive Behaviour for the Preschool Children: a Double-blinded Randomized Controlled Cross-over Study

Read the detailed description

Gut inflammation is reflected by serum C-Reactive Protein (CRP), hemoglobin (HB), interleukin-4 (IL-4), Immunoglobulin G (IgG), Immunoglobulin E (IgE), Immunoglobulin G1 (IgG1), Immunoglobulin G2a (IgG2a), β-Casomorphin-7 (BCM-7), Glutathione, calcium (Ca), iron (Fe) and zinc (Zn) concentration; gastrointestinal (GI) symptoms are measured via Visual Analog Scale (VAS) for gut tolerance, including borborygmus, bloating, break wind, abdominal pain, and diarrhea; behavioral well-being is assessed using Subtle Cognitive Impairment Test (SCIT).

The total duration of study was 24 weeks, including subject enrollment, study intervention, laboratory testing, and providing clinical study report. The cross-over study consisted of 5 days of each product intervention; 10 days of wash-out in phase 1 and phase 2, respectively; and then followed by 6 weeks of statistical analysis and clinical report completion.

Conditions: Gut Inflammation
Being tested: Oral consumption of milk A1 in study phase 1, Oral consumption of milk A2 in study phase 1, Oral consumption of milk A1 in study phase 2, Oral consumption of milk A2 in study phase 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Oral consumption of milk A1 in study phase 1Dietary supplement
Oral consumption of 250 ml of milk containing both A1 and A2 type beta casein 2 times per day after meal for 5 days in study phase 1.
Oral consumption of milk A2 in study phase 1Dietary supplement
Oral consumption of 250 ml of milk containing only A2 type beta casein 2 times per day after meal for 5 days in study phase 1.
Oral consumption of milk A1 in study phase 2Dietary supplement
Oral consumption of 250 ml of milk containing both A1 and A2 type beta casein 2 times per day after meal for 5 days in study phase 2.
Oral consumption of milk A2 in study phase 2Dietary supplement
Oral consumption of 250 ml of milk containing only A2 type beta casein 2 times per day after meal for 5 days in study phase 2.

Study groups in NCT03081845
Study group	Role	What they receive
Sequence A1-A2	Experimental	Oral consumption of milk A1 in study phase 1. Oral consumption of milk A2 in study phase 2. Receives: Dietary Supplement: Oral consumption of milk A1 in study phase 1; Dietary Supplement: Oral consumption of milk A2 in study phase 2
Sequence A2-A1	Experimental	Oral consumption of milk A2 in study phase 1. Oral consumption of milk A1 in study phase 2. Receives: Dietary Supplement: Oral consumption of milk A2 in study phase 1; Dietary Supplement: Oral consumption of milk A1 in study phase 2

What is being measured

The primary outcome is the main question the study is designed to answer.

Change from baseline of gastrointestinal symptom VAS scores
were self-measured by study subjects on a scale from 0 (never) to 3 (always) at baseline (day 1 for phase 1 and day 15 for phase 2, before product consumption) and at the end of the 5-day product consumption (day 5 for phase 1 and day 19 for phase 2).
Measured: Baseline (day 1 for phase 1 and day 15 for phase 2, before product consumption), at the end of the 5-day product consumption (day 5 for phase 1 and day 19 for phase 2)

Secondary outcomes (17)

Stool frequency
In each study phase, the number of defecation per day measured during the last 5 days of wash-out period (day -4, -3, -2, -1, 0 in phase 1 and day 10, 11, 12, 13, 14 in phase 2) and the 5 days of product intervention (day 1, 2, 3, 4, 5 in phase 1 and day 15, 16, 17, 18, 19 in phase 2).
Measured: Day -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19
Stool consistency
In each study phase, the score of stool consistency assessed using Bristol Stool Chart during the last 5 days of wash-out period (day -4, -3, -2, -1, 0 in phase 1 and day 10, 11, 12, 13, 14 in phase 2) and the 5 days of product intervention (day 1, 2, 3, 4, 5 in phase 1 and day 15, 16, 17, 18, 19 in phase 2).
Measured: Day -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 5, 16, 17, 18, 19
Serum C-reactive protein (CRP) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Hemoglobin (HGB) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Interleukin-4 (IL-4) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Immunoglobulin G (IgG) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Immunoglobulin E (IgE) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Immunoglobulin G1 (IgG1) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Immunoglobulin G2a (IgG2a) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum β-Casomorphin-7 (BCM-7) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Glutathione concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum calcium (Ca) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum iron (Fe) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum zinc (Zn) concentration
Only measured in phase 1
Measured: Day 1 before intervention (baseline), and day 5 (post-intervention)
Fecal short chain fatty acids (SCFA) concentration
Measured at baseline and post-intervention in each study phase
Measured: Day 1, Day 5, Day 15, Day 19
myeloperoxidase (MPO)
Measured at baseline and post-intervention in each study phase
Measured: Day 1, Day 5, Day 15, Day 19
Subtle Cognitive Impairment Test (SCIT)
Subject response time and error rate at stimulus exposure duration of 16, 32, 48, 64, 80, 96, 112 and 128 millisecond, as well as their head and tail means were recorded at baseline (day 1 for phase 1 and day 15 for phase 2) and the end of intervention (day 5 for phase 1 and day 19 for phase 2).
Measured: 16, 32, 48, 64, 80, 96, 112 and 128 millisecond on day 1; 16, 32, 48, 64, 80, 96, 112 and 128 millisecond on day 5; 16, 32, 48, 64, 80, 96, 112 and 128 millisecond on day 15; 16, 32, 48, 64, 80, 96, 112 and 128 millisecond on day 19

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Sep 201620 Jan 2017

First posted16 Mar 2017
Study start13 Sep 2016
Primary completion14 Oct 2016
Study completion20 Jan 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Gut InflammationStudies 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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03081845
Sponsor's protocol ID: 15-SC-5-A2-002
Status last verified: Mar 2017
First submitted: 28 Feb 2017
Last updated: 16 Mar 2017
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Sheng X, Li Z, Ni J, Yelland G. Effects of Conventional Milk Versus Milk Containing Only A2 beta-Casein on Digestion in Chinese Children: A Randomized Study. J Pediatr Gastroenterol Nutr. 2019 Sep;69(3):375-382. doi: 10.1097/MPG.0000000000002437.
PubMed 31305326

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 16 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparative Effects of A1 Versus A2® Milk on the Gastrointestinal Physiology, Symptoms and Cognitive Behaviour for the Preschool Children: a Double-blinded Randomized Controlled Cross-over Study
ClinicalTrials.gov ID: NCT03081845
Acronym / sponsor ID: 15-SC-5-A2-002
Conditions: Gut Inflammation
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (actual)
Lead sponsor: a2 Milk Company Ltd.Industry (pharma, biotech, devices)
Study start: 13 Sep 2016 (actual)
Primary completion: 14 Oct 2016 (actual)
Study completion: 20 Jan 2017 (actual)
First posted: 16 Mar 2017 (actual)
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.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Sequence A1-A2	Experimental	Dietary Supplement: Oral consumption of milk A1 in study phase 1, Dietary Supplement: Oral consumption of milk A2 in study phase 2Oral consumption of milk A1 in study phase 1. Oral consumption of milk A2 in study phase 2.
Sequence A2-A1	Experimental	Dietary Supplement: Oral consumption of milk A2 in study phase 1, Dietary Supplement: Oral consumption of milk A1 in study phase 2Oral consumption of milk A2 in study phase 1. Oral consumption of milk A1 in study phase 2.

Who may qualify

Ages: 5 to 6 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child

Key inclusion criteria (6 listed)

Non-regular milk drinker;
Suffered from mild to moderate milk intolerance;
Agree not to take any medication, supplements, nutrition or other dairy products including acidophilus milk;
Parent(s) or legal guardian's consent to the study and willing to comply with study procedures;
Parent(s) or guardian of infant agrees not to enroll infant another clinical study while participating in this study;

Key exclusion criteria (12 listed)

Have known dairy allergy;
Suffered from severe milk intolerance;
Unable to give written informed consent;
Use of antibiotics at the time of screening, or during the past two weeks;
Have history of fecal impaction;

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 of milk A1 in study phase 1Oral consumption of 250 ml of milk containing both A1 and A2 type beta casein 2 times per day after meal for 5 days in study phase 1.	Dietary supplement	Sequence A1-A2
Oral consumption of milk A2 in study phase 1Oral consumption of 250 ml of milk containing only A2 type beta casein 2 times per day after meal for 5 days in study phase 1.	Dietary supplement	Sequence A2-A1
Oral consumption of milk A1 in study phase 2Oral consumption of 250 ml of milk containing both A1 and A2 type beta casein 2 times per day after meal for 5 days in study phase 2.	Dietary supplement	Sequence A2-A1
Oral consumption of milk A2 in study phase 2Oral consumption of 250 ml of milk containing only A2 type beta casein 2 times per day after meal for 5 days in study phase 2.	Dietary supplement	Sequence A1-A2

Primary outcome

Change from baseline of gastrointestinal symptom VAS scores
Time frame: Baseline (day 1 for phase 1 and day 15 for phase 2, before product consumption), at the end of the 5-day product consumption (day 5 for phase 1 and day 19 for phase 2)
were self-measured by study subjects on a scale from 0 (never) to 3 (always) at baseline (day 1 for phase 1 and day 15 for phase 2, before product consumption) and at the end of the 5-day product consumption (day 5 for phase 1 and day 19 for phase 2).

17 secondary outcomes

Stool frequency
Time frame: Day -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19
Stool consistency
Time frame: Day -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 5, 16, 17, 18, 19
Serum C-reactive protein (CRP) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Hemoglobin (HGB) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Interleukin-4 (IL-4) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Immunoglobulin G (IgG) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Immunoglobulin E (IgE) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Immunoglobulin G1 (IgG1) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Immunoglobulin G2a (IgG2a) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum β-Casomorphin-7 (BCM-7) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum Glutathione concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum calcium (Ca) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum iron (Fe) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Serum zinc (Zn) concentration
Time frame: Day 1 before intervention (baseline), and day 5 (post-intervention)
Fecal short chain fatty acids (SCFA) concentration
Time frame: Day 1, Day 5, Day 15, Day 19
myeloperoxidase (MPO)
Time frame: Day 1, Day 5, Day 15, Day 19
Subtle Cognitive Impairment Test (SCIT)
Time frame: 16, 32, 48, 64, 80, 96, 112 and 128 millisecond on day 1; 16, 32, 48, 64, 80, 96, 112 and 128 millisecond on day 5; 16, 32, 48, 64, 80, 96, 112 and 128 millisecond on day 15; 16, 32, 48, 64, 80, 96, 112 and 128 millisecond on day 19

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 16 Mar 2017.
Derived from this study: PubMed 31305326Sheng X, Li Z, Ni J, Yelland G. Effects of Conventional Milk Versus Milk Containing Only A2 beta-Casein on Digestion in Chinese Children: A Randomized Study. J Pediatr Gastroenterol Nutr. 2019 Sep;69(3):375-382. doi: 10.1097/MPG.0000000000002437.
Individual participant dataSharing planned: No

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Not yet recruiting
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Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
Not yet recruiting
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Not yet recruiting
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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.

Li Zhang, MD study director

Sprim (Shanghai) Consulting Co., Ltd.

Questions about this trial

What is this clinical trial studying?

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 6 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 16 Mar 2017. 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. 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?

Change from baseline of gastrointestinal symptom VAS scores (time frame: Baseline (day 1 for phase 1 and day 15 for phase 2, before product consumption), at the end of the 5-day product consumption (day 5 for phase 1 and day 19 for phase 2)). 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 NCT03081845, which also lists 1 linked publication.

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 16 Mar 2017.