Double Crossover Casein Type Tolerance Trial

NCT ID: NCT06315517

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-20
• Study Completion Date: 2024-07-31

Brief Summary

The investigators will recruit 45 fluid milk avoiding adults to participate in a five-week double-blind, double-crossover study in which the physiological responses to increasing doses of lactose-free (A1-rich milk), A2 milk, and lactose-free A2 milk will be explored.

Detailed Description

Dairy provides essential nutrients and dairy products and are among the best quality and bioavailable protein sources available to humans. Milk protein allergy is extremely rare outside of childhood, and lactose intolerance is highly variable among ethnicities. Nonetheless, many adults avoid fluid milk and dairy products unnecessarily. Recent studies suggest that dairy intolerant individuals are having gastrointestinal reactions specifically to the bioactive metabolites (specifically, beta-casomorphin-7[BCM-7]) of casein protein subtype A1, and consuming milk void of A1 and rich in A2 casein alleviates symptoms.

The investigators will recruit 45 fluid milk avoiding adults to participate in a five-week double-blind, double-crossover study in which physiological responses to increasing doses of lactose-free (A1-rich milk), A2 milk, and lactose-free A2 milk will be explored. Enrollment assessments will include a comprehensive metabolic panel, diet history, and medical history questionnaires. Stool samples will be collected at the beginning and end of each of the 3 test phases (6 total samples per participant). Each test phase will last 6 days long, during which participants will receive increased doses of casein every 2 days.

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Conditions

Dairy Intolerance; Healthy Adults

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Conventional lactose-free milk first

Participants will consume conventional lactose-free milk first, then each of the other milk types in random order

Group Type: EXPERIMENTAL

Conventional lactose-free cow's milk

Intervention Type: OTHER

Participants will receive conventional lactose-free cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Nonconventional (A2) cow's milk

Intervention Type: OTHER

Participants will receive nonconventional (A2) cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Nonconventional (A2) lactose-free cow's milk

Intervention Type: OTHER

Participants will receive nonconventional (A2) lactose-free cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Non-conventional (A2) lactose-free milk first

Participants will consume non-conventional (A2) lactose-free milk first, then each of the other milk types in random order

Group Type: EXPERIMENTAL

Conventional lactose-free cow's milk

Intervention Type: OTHER

Participants will receive conventional lactose-free cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Nonconventional (A2) cow's milk

Intervention Type: OTHER

Participants will receive nonconventional (A2) cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Nonconventional (A2) lactose-free cow's milk

Intervention Type: OTHER

Participants will receive nonconventional (A2) lactose-free cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Non-conventional (A2) milk first

Participants will consume non-conventional (A2) milk first, then each of the other milk types in random order

Group Type: EXPERIMENTAL

Conventional lactose-free cow's milk

Intervention Type: OTHER

Participants will receive conventional lactose-free cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Nonconventional (A2) cow's milk

Intervention Type: OTHER

Participants will receive nonconventional (A2) cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Nonconventional (A2) lactose-free cow's milk

Intervention Type: OTHER

Participants will receive nonconventional (A2) lactose-free cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Interventions

Conventional lactose-free cow's milk

Participants will receive conventional lactose-free cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Intervention Type: OTHER

Nonconventional (A2) cow's milk

Participants will receive nonconventional (A2) cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Intervention Type: OTHER

Nonconventional (A2) lactose-free cow's milk

Participants will receive nonconventional (A2) lactose-free cow's milk as follows:

On Day 1, participants will receive 50mg casein/kg/bw (~125ml milk). On Day 3, participants will receive 100mg casein/kg/bw (~250ml milk). On Day 5, participants will received 200mg casein/kg/bw (~500ml milk). During test phases, breath hydrogen and methane will be measured every thirty minutes for three hours, and blood glucose will be measured every thirty minutes for two hours. Gastrointestinal symptoms will be assessed with visual analog scales for the following 24 hours. There will be a 7-10 day wash out period in between test phases.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adults age 18+
• Currently avoid liquid milk
• Can read and speak English

Exclusion Criteria

• Diagnosis of milk protein allergy
• Diagnosis of Crohn's Disease, Ulcerative Colitis, Celiac Disease, or Peptic Ulcer Disease or Gastroparesis
• Using antibiotic or antiviral medications within 30 days prior to study start
• Undergoing chemotherapy, or using any investigational drugs within 30 days prior to study start
• Pregnant or lactating

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Auburn University

OTHER

Sponsor Role: lead

Responsible Party

Andrew Fruge

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew D Frugé, PhD

Role: PRINCIPAL_INVESTIGATOR

Auburn University

Locations

Auburn University

Auburn, Alabama, United States

Countries

United States

Other Identifiers

1792-23P

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

23-552 MR 2404

Identifier Type: -

Identifier Source: org_study_id