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.
