Clinical trial NCT06315517: Double Crossover Casein Type Tolerance Trial
Official title: A Randomized Controlled Crossover Trial to Assess Tolerance, Gastrointestinal Distress & Preference for Milks Varying in Casein Types & Lactose Content
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dairy Intolerance
Healthy Adults
Keywords: A2 casein
A1 casein
fluid milk
lactose
dairy
Lead sponsor: Auburn University
Sponsor class: OTHER
First posted: 2024-03-18
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized controlled, double-blinded, double-crossover trial
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Gastrointestinal Distress Scores
timeFrame: 24 hours after each sample challenge
Secondary outcomes:
measure: Breath Hydrogen (ppm)
timeFrame: Three hours after each sample challenge
measure: Breath Methane (ppm)
timeFrame: Three hours after each sample challenge
measure: Blood Glucose (mg/dl)
timeFrame: Two hours after each sample challenge
measure: Stool microbiome composition
timeFrame: One week after each sample challenge
measure: Stool Beta-casomorphin-7 (BCM-7)
timeFrame: One week after each sample challenge
measure: Stool intestinal fatty acid binding protein (I-FABP)
timeFrame: One week after each sample challenge
Other outcomes:
Locations:
city: Auburn
country: United States
facility: Auburn University
state: Alabama
Study officials:
affiliation: Auburn University
name: Andrew D Frugé, PhD
role: PRINCIPAL_INVESTIGATOR
References: