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Double Crossover Casein Type Tolerance Trial

Not Applicable
Completed
Conditions
Healthy Adults
Dairy Intolerance
Interventions
Other: Conventional lactose-free cow's milk
Other: Nonconventional (A2) cow's milk
Other: Nonconventional (A2) lactose-free cow's milk
Registration Number
NCT06315517
Lead Sponsor
Auburn University
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Conventional lactose-free milk firstNonconventional (A2) cow's milkParticipants will consume conventional lactose-free milk first, then each of the other milk types in random order
Non-conventional (A2) lactose-free milk firstConventional lactose-free cow's milkParticipants will consume non-conventional (A2) lactose-free milk first, then each of the other milk types in random order
Conventional lactose-free milk firstConventional lactose-free cow's milkParticipants will consume conventional lactose-free milk first, then each of the other milk types in random order
Non-conventional (A2) lactose-free milk firstNonconventional (A2) cow's milkParticipants will consume non-conventional (A2) lactose-free milk first, then each of the other milk types in random order
Non-conventional (A2) milk firstNonconventional (A2) cow's milkParticipants will consume non-conventional (A2) milk first, then each of the other milk types in random order
Conventional lactose-free milk firstNonconventional (A2) lactose-free cow's milkParticipants will consume conventional lactose-free milk first, then each of the other milk types in random order
Non-conventional (A2) lactose-free milk firstNonconventional (A2) lactose-free cow's milkParticipants will consume non-conventional (A2) lactose-free milk first, then each of the other milk types in random order
Non-conventional (A2) milk firstConventional lactose-free cow's milkParticipants will consume non-conventional (A2) milk first, then each of the other milk types in random order
Non-conventional (A2) milk firstNonconventional (A2) lactose-free cow's milkParticipants will consume non-conventional (A2) milk first, then each of the other milk types in random order
Primary Outcome Measures
NameTimeMethod
Gastrointestinal Distress Scores24 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 Outcome Measures
NameTimeMethod
Blood Glucose (mg/dl)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.

Stool Beta-casomorphin-7 (BCM-7)One week after each sample challenge

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

Breath Hydrogen (ppm)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.

Breath Methane (ppm)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.

Stool microbiome compositionOne week after each sample challenge

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

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

Trial Locations

Locations (1)

Auburn University

🇺🇸

Auburn, Alabama, United States

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