Double Crossover Casein Type Tolerance Trial

A Randomized Controlled Crossover Trial to Assess Tolerance, Gastrointestinal Distress & Preference for Milks Varying in Casein Types & Lactose Content

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Adults; Dairy Intolerance
• Intervention / Treatment: Other: Conventional lactose-free cow's milk; Other: Nonconventional (A2) cow's milk; Other: Nonconventional (A2) lactose-free cow's milk

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.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrew D Frugé, PhD; Phone Number: 3348448433; Email: adf0003@auburn.edu
• Study Contact Backup: Name: Laura Robinson, MS; Phone Number: 9084423688; Email: lad0030@auburn.edu

Study Locations

• United States
  • Alabama
    • Auburn, Alabama, United States, 36849
      • Auburn University
      • Contact: Andrew D Frugé, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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
• Alcohol intake >28 servings/week
• Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Conventional lactose-free milk first; Participants will consume conventional lactose-free milk first, then each of the other milk types in random order	Other: 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.; 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.; 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.
Experimental: 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	Other: 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.; 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.; 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.
Experimental: Non-conventional (A2) milk first; Participants will consume non-conventional (A2) milk first, then each of the other milk types in random order	Other: 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.; 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gastrointestinal Distress Scores	Changes in gastrointestinal distress measured via visual analog scales that range from 0 (no symptoms) to 100 cm (severe symptoms). Lower values are optimal.	24 hours after each sample challenge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breath Hydrogen (ppm)	Breath hydrogen will be measured via QuinTron BreathTracker SC Analyzer every 30 minutes for three hours beginning immediately prior to each sample challenge. Lower levels are optimal.	Three hours after each sample challenge
Breath Methane (ppm)	Breath methane will be measured via QuinTron BreathTracker SC Analyzer every 30 minutes for three hours beginning immediately prior to each sample challenge. Lower levels are optimal.	Three hours after each sample challenge
Blood Glucose (mg/dl)	Capillary finger sticks will determine blood glucose levels for two hours beginning immediately prior to each sample challenge. Minimal deviations from baseline are optimal.	Two hours after each sample challenge
Stool microbiome composition	16S changes in microbiome alpha diversity. Higher levels are optimal.	One week after each sample challenge
Stool Beta-casomorphin-7 (BCM-7)	Fecal samples preserved in aqueous solution will be analyzed for casein metabolite, BCM-7. Lower levels are optimal.	One week after each sample challenge
Stool intestinal fatty acid binding protein (I-FABP)	Fecal samples preserved in aqueous solution will be analyzed for intestinal permeability marker, I-FABP. Lower levels are optimal.	One week after each sample challenge

Collaborators and Investigators

• Sponsor: Auburn University
• Investigators: Principal Investigator: Andrew D Frugé, PhD, Auburn University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 2, 2024
• First Submitted That Met QC Criteria: March 11, 2024
• First Posted (Actual): March 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: dairy; lactose; A2 casein; A1 casein; fluid milk
• Other Study ID Numbers: AU24; 1792-23P (Other Grant/Funding Number: The Dairy Alliance)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No