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Completed

NCT Number: NCT06315517

Double Crossover Casein Type Tolerance Trial

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.

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Key information

Age range

18 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Auburn University

Auburn, Alabama, 36849, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Conventional lactose-free cow's milk

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

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

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.

Primary outcomes

  1. Gastrointestinal Distress Scores

    Time frame: 24 hours after each sample challenge

    Changes in gastrointestinal distress measured via visual analog scales that range from 0 (no symptoms) to 100 cm (severe symptoms). Lower values are optimal.

Secondary outcomes

  1. Breath Hydrogen (ppm)

    Time frame: Three hours after each sample challenge

    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.

  2. Breath Methane (ppm)

    Time frame: Three hours after each sample challenge

    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.

  3. Blood Glucose (mg/dl)

    Time frame: Two hours after each sample challenge

    Capillary finger sticks will determine blood glucose levels for two hours beginning immediately prior to each sample challenge. Minimal deviations from baseline are optimal.

  4. Stool microbiome composition

    Time frame: One week after each sample challenge

    16S changes in microbiome alpha diversity. Higher levels are optimal.

  5. Stool Beta-casomorphin-7 (BCM-7)

    Time frame: One week after each sample challenge

    Fecal samples preserved in aqueous solution will be analyzed for casein metabolite, BCM-7. Lower levels are optimal.

  6. Stool intestinal fatty acid binding protein (I-FABP)

    Time frame: One week after each sample challenge

    Fecal samples preserved in aqueous solution will be analyzed for intestinal permeability marker, I-FABP. Lower levels are optimal.

Sponsors and collaborators

Lead sponsor

Auburn University

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2024
Study completion
2024
First posted
Mar 18, 2024
Registry last updated
Apr 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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