Double Crossover Casein Type Tolerance Trial

Healthy Adults Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06315517
• Other study ID #: 23-552 MR 2404
• Secondary ID: 1792-23P
• Status: Recruiting
• Phase: N/A
• Start date: April 20, 2024
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: Auburn University
• Contact: Andrew D Frugé, PhD
• Phone: 3348448433
• Email: adf0003[@]auburn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Dairy Intolerance
• Healthy Adults

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Auburn University	Auburn	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
Auburn University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Stool microbiome composition	16S changes in microbiome alpha diversity. Higher levels are optimal.	One week after each sample challenge
Secondary	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
Secondary	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