Clinical trial NCT06252636: Evaluation of the Efficacy and Safety of A2 Milk on Digestion
Official title: An 8-week, Randomized, Double-Blind, Crossover, Placebo-Controlled Trial for the Evaluation of the Efficacy and Safety of A2 Milk on Digestion
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Digestive Discomfort
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
First posted: 2024-02-12
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: The aim of this study is to evaluate the efficacy and safety of A2 milk versus a control (A1/A2 milk) in individuals with digestive discomfort following milk consumption.

Detailed description: Milk has a high calcium content, and calcium in milk is easily digested and absorbed and has an excellent utilization rate in the body. Milk is rich in lactose, Vitamin D, and peptides that facilitate calcium absorption, and it also contains essential amino acids and bioactive substances that are beneficial to health. Regularly drinking milk has been proven to improve insulin sensitivity, blood pressure, and serum lipid concentrations. Furthermore, milk is reported to be an effective food for nutritional supplementation and improvement in the diet of Koreans, as it contains a well-balanced source of essential amino acids that can be lacking in a rice-centric diet, along with quality animal protein, calcium, vitamin B2, and other nutrients. However, this increase in dairy consumption can be associated with an increased risk for certain disorders, including digestive disorders.

The actual prevalence of lactose intolerance is unclear in Korea, and reports have ranged from 39.1% to 84.1%. In 2010, it was reported that in most individuals who believed they had lactose intolerance, no evidence of problems with lactose absorption could be found, and thus, gastrointestinal symptoms were unlikely to be associated with lactose. Alternatively, A1 β-Casein and β-Casomorphin-7 (BCM-7) has emerged as a major area for research in relation to digestive discomfort following milk consumption.

Milk is composed of 80% Casein protein and 20% whey. Among Casein proteins, β-Casein can be divided into the A1 type comprised of A1, B, C, F, and G, and the A2 type with A2, A3, D, E, H, I, and J variants. A1 and A2 type β-Casein proteins differ in their 67th amino acid, with A1 containing Histidine and B2 with Proline. The other remaining variants are only found in low levels or not found in European cattle. Furthermore, BCM-7, which is produced when enzymatic cleavage at the histidine position occurs in A1 β-Casein, has been associated with digestive discomfort. Additionally, milk containing A1 β-Casein has been linked to type 1 diabetes and heart disease. Nevertheless, the majority of dairy cattle in dairy industries continue to produce milk containing A1 β-Casein.

Animal tests have shown that milk with A1 β-Casein takes longer to transit through the digestive tract compared to A2 β-Casein containing milk. In addition, a clinical trial reported that the Bristol stool scores in participants who consumed A1 β-Casein milk were higher than those in A2 β-Casein milk. Another clinical trial announced that A2 β-Casein milk alleviated gastrointestinal symptoms of milk hypersensitivity.

Therefore, this study aims to evaluate the efficacy and safety of A2 milk compared to a control (A1/A2 milk) in individuals who experience discomfort after consuming milk.

Eligibility criteria: Inclusion Criteria:

1. Between 20 to 70 years of age
2. Participants who are experiencing digestive symptoms (bloating, gas, heaviness, abdominal pain, gurgling stomach, belching, bowel urgency) following milk consumption on Visit 1 with each score on the digestive discomfort symptom survey being 2 points or less. (Individuals who have indicated 0 in all symptoms or 3 in at least one symptom will be excluded.)
3. Those who have agreed to participate and given written consent through the Informed Consent Form prior to the study

Exclusion Criteria:

1. Currently undergoing treatment for severe cardiovascular, immune, respiratory, gastrointestinal/hepatic and biliary, renal and urinary, neurological, musculoskeletal, mental, infectious, metabolic diseases, and malignancies
2. Diagnosed with or has a history of gastrointestinal diseases (irritable bowel syndrome, colitis, ulcerative colitis, abdominal diseases etc.), or has undergone gastrointestinal surgery
3. Individuals with severe lactose intolerance
4. History of bowel obstruction
5. Alcohol addiction or substance abuse
6. Hospitalized within the last 3 months of Visit 1
7. Has taken medication affecting body weight {anti-obesity drugs (appetite suppressants, fat absorption inhibitors, Glucagon-like peptide-1 (GLP-1) receptor agonists etc.), psychiatric drugs such as antidepressants and antipsychotics, diuretics, contraceptives, steroids, female hormones, thyroid hormones} within the last 3 months of Visit 1
8. Has taken immunosuppressive drugs or anti-inflammatory drugs within the last month (30 days) of Visit 1
9. Administered antibiotics or laxatives within the last 2 weeks of Visit 2
10. Has taken prokinetics (Serotonin type 4 (5-HT4) Agonist, D2 Antagonists, Cholinergic Agonists etc.), laxatives {fiber supplements (Psyllium, Methylcellulose etc.), stool softeners, osmotic laxatives (Sorbitol, Lactulose etc.), stimulant laxatives (Bisacodyl, Anthraquinone etc.)}
11. Pregnant, breastfeeding, or planning to become pregnant during the study period
12. Allergic to dairy products
13. Participated in another interventional clinical trial (including human trials) within the last 3 months of Visit 1, or planning to participate in another interventional clinical trial (including human trials) after the start of this study
14. Individuals deemed inappropriate for the study by the investigator

Primary outcomes:
measure: Gastrointestinal Symptom Rating Scale (GSRS) Total Score
timeFrame: Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
Secondary outcomes:
measure: Upper Abdominal Gastrointestinal Symptom Rating Scale (GSRS) Score
timeFrame: Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Lower Abdominal (Gastrointestinal Symptom Rating Scale) GSRS Score
timeFrame: Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Digestive Discomfort Symptom Survey
timeFrame: Surveys given on Screening (week -2), Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4) to record daily; Retrieved on Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Bowel Frequency and Form
timeFrame: Journal provided on Screening (week -2), Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4) to record daily; Retrieved on Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Blood Marker - High Sensitive C-reactive protein (hs-CRP)
timeFrame: Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Blood marker - Interleukin-4 (IL-4)
timeFrame: Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Blood marker - Immunoglobulin G (IgG) and Immunoglobulin G1 (IgG1)
timeFrame: Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Blood marker - Immunoglobulin E (IgE)
timeFrame: Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Blood marker - β-casomorphin-7 (BCM-7)
timeFrame: Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Stool marker - Short-chain Fatty Acid (SCFA)
timeFrame: Stool collection kit provided on Screening (week -2), Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4); Retrieved on Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Stool marker - Calprotectin
timeFrame: Stool collection kit provided on Screening (week -2), Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4); Retrieved on Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
measure: Stool marker - Microbiome
timeFrame: Stool collection kit provided on Screening (week -2), Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4); Retrieved on Visit 2 (week 0), Visit 3 (week 2), Visit 4 (week 4), Visit 5 (week 6)
Other outcomes:
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
Study officials:
affiliation: Seoul National University Bundang Hospital
name: Nayoung Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: