Clinical trial NCT03081845: A1 Versus A2® Milk on the Gastrointestinal Physiology, Symptoms and Cognitive Behaviour for the Preschool Children
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gut Inflammation
Lead sponsor: a2 Milk Company Ltd.
Sponsor class: INDUSTRY
First posted: 2017-03-16
Enrollment: 80
Sex: ALL
Minimum age (years): 5
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;
* 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.

Primary outcomes:
measure: Change from baseline of gastrointestinal symptom VAS scores
timeFrame: 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:
measure: Stool frequency
timeFrame: Day -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19
measure: Stool consistency
timeFrame: Day -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 5, 16, 17, 18, 19
measure: Serum C-reactive protein (CRP) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum Hemoglobin (HGB) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum Interleukin-4 (IL-4) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum Immunoglobulin G (IgG) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum Immunoglobulin E (IgE) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum Immunoglobulin G1 (IgG1) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum Immunoglobulin G2a (IgG2a) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum β-Casomorphin-7 (BCM-7) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum Glutathione concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum calcium (Ca) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum iron (Fe) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Serum zinc (Zn) concentration
timeFrame: Day 1 before intervention (baseline), and day 5 (post-intervention)
measure: Fecal short chain fatty acids (SCFA) concentration
timeFrame: Day 1, Day 5, Day 15, Day 19
measure: myeloperoxidase (MPO)
timeFrame: Day 1, Day 5, Day 15, Day 19
measure: Subtle Cognitive Impairment Test (SCIT)
timeFrame: 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
Other outcomes:
Locations:
Study officials:
affiliation: Sprim (Shanghai) Consulting Co., Ltd.
name: Li Zhang, MD
role: STUDY_DIRECTOR
References:
citation: 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.