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

Gut Inflammation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03081845
• Other study ID #: 15-SC-5-A2-002
• Status: Completed
• Phase: Phase 4
• First received: February 28, 2017
• Last updated: March 10, 2017
• Start date: September 13, 2016
• Est. completion date: January 20, 2017

Study information

• Verified date: March 2017
• Source: a2 Milk Company Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: January 20, 2017
• Est. primary completion date: October 14, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years to 6 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gut Inflammation
• Inflammation

Intervention

Dietary Supplement:
• Oral consumption of milk A1 in study phase 1
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 1
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 2
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 2
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
a2 Milk Company Ltd.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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	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).	Day -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19
Secondary	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).	Day -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 10, 11, 12, 13, 14, 5, 16, 17, 18, 19
Secondary	Serum C-reactive protein (CRP) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum Hemoglobin (HGB) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum Interleukin-4 (IL-4) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum Immunoglobulin G (IgG) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum Immunoglobulin E (IgE) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum Immunoglobulin G1 (IgG1) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum Immunoglobulin G2a (IgG2a) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum ß-Casomorphin-7 (BCM-7) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum Glutathione concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum calcium (Ca) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum iron (Fe) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Serum zinc (Zn) concentration	Only measured in phase 1	Day 1 before intervention (baseline), and day 5 (post-intervention)
Secondary	Fecal short chain fatty acids (SCFA) concentration	Measured at baseline and post-intervention in each study phase	Day 1, Day 5, Day 15, Day 19
Secondary	myeloperoxidase (MPO)	Measured at baseline and post-intervention in each study phase	Day 1, Day 5, Day 15, Day 19
Secondary	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).	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