Dairy IntoleranceNCT06315517
Double Crossover Casein Type Tolerance Trial
A study testing Conventional lactose-free cow's milk, Nonconventional (A2) cow's milk and Nonconventional (A2) lactose-free cow's milk in people with Dairy Intolerance and Healthy Adults, run by Auburn University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Dairy Intolerance, Healthy Adults
- What is being tested?
- Conventional lactose-free cow's milk, Nonconventional (A2) cow's milk and Nonconventional (A2) lactose-free cow's milk
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Apr 2024to 31 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults age 18+
- Currently avoid liquid milk
- Can read and speak English
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Dairy Intolerance, Healthy Adults
- Being tested
- Conventional lactose-free cow's milk, Nonconventional (A2) cow's milk, Nonconventional (A2) lactose-free cow's milk
- Keywords
- A2 casein, A1 casein, fluid milk, lactose, dairy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional lactose-free cow's milkOther
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 milkOther
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 milkOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Conventional lactose-free milk first | Experimental | Participants will consume conventional lactose-free milk first, then each of the other milk types in random order Receives: Other: Conventional lactose-free cow's milk; Other: Nonconventional (A2) cow's milk; Other: Nonconventional (A2) lactose-free cow's milk |
| Non-conventional (A2) lactose-free milk first | Experimental | Participants will consume non-conventional (A2) lactose-free milk first, then each of the other milk types in random order Receives: Other: Conventional lactose-free cow's milk; Other: Nonconventional (A2) cow's milk; Other: Nonconventional (A2) lactose-free cow's milk |
| Non-conventional (A2) milk first | Experimental | Participants will consume non-conventional (A2) milk first, then each of the other milk types in random order Receives: Other: Conventional lactose-free cow's milk; Other: Nonconventional (A2) cow's milk; Other: Nonconventional (A2) lactose-free cow's milk |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours after each sample challenge
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: Two hours after each sample challenge
Stool microbiome composition
16S changes in microbiome alpha diversity. Higher levels are optimal.
Measured: 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.
Measured: 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.
Measured: One week after each sample challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2024
- Study start20 Apr 2024
- Primary completion26 Jul 2024
- Study completion31 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dairy IntoleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized controlled, double-blinded, double-crossover trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Auburn University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrew Fruge, Auburn University
- Investigators
- Andrew D Frugé, PhD, Principal investigator, Auburn University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06315517
- Sponsor's protocol ID
- 23-552 MR 2404
- Other IDs
- 1792-23P
- Status last verified
- Apr 2025
- First submitted
- 2 Mar 2024
- Last updated
- 4 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Crossover Trial to Assess Tolerance, Gastrointestinal Distress & Preference for Milks Varying in Casein Types & Lactose Content
- ClinicalTrials.gov ID
- NCT06315517
- Acronym / sponsor ID
- 23-552 MR 2404
- Conditions
- Dairy Intolerance, Healthy Adults
- Keywords
- A2 casein, A1 casein, fluid milk, lactose, dairy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Auburn UniversityUniversity, hospital or other
- Study start
- 20 Apr 2024 (actual)
- Primary completion
- 26 Jul 2024 (actual)
- Study completion
- 31 Jul 2024 (actual)
- First posted
- 18 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Randomized controlled, double-blinded, double-crossover trial
| Arm | Type | Receives |
|---|---|---|
| Conventional lactose-free milk first | Experimental | Other: Conventional lactose-free cow's milk, Other: Nonconventional (A2) cow's milk, Other: Nonconventional (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 first | Experimental | Other: Conventional lactose-free cow's milk, Other: Nonconventional (A2) cow's milk, Other: Nonconventional (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 first | Experimental | Other: Conventional lactose-free cow's milk, Other: Nonconventional (A2) cow's milk, Other: Nonconventional (A2) lactose-free cow's milkParticipants will consume non-conventional (A2) milk first, then each of the other milk types in random order |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults age 18+
- Currently avoid liquid milk
- Can read and speak English
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Conventional lactose-free cow's milkParticipants 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 | Conventional lactose-free milk first, Non-conventional (A2) lactose-free milk first, Non-conventional (A2) milk first |
| Nonconventional (A2) cow's milkParticipants 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 | Conventional lactose-free milk first, Non-conventional (A2) lactose-free milk first, Non-conventional (A2) milk first |
| Nonconventional (A2) lactose-free cow's milkParticipants 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. | Other | Conventional lactose-free milk first, Non-conventional (A2) lactose-free milk first, Non-conventional (A2) milk first |
Primary outcome
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.
6 secondary outcomes
Breath Hydrogen (ppm)
Time frame: Three hours after each sample challenge
Breath Methane (ppm)
Time frame: Three hours after each sample challenge
Blood Glucose (mg/dl)
Time frame: Two hours after each sample challenge
Stool microbiome composition
Time frame: One week after each sample challenge
Stool Beta-casomorphin-7 (BCM-7)
Time frame: One week after each sample challenge
Stool intestinal fatty acid binding protein (I-FABP)
Time frame: One week after each sample challenge
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew D Frugé, PhD principal investigator
Auburn University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Conventional lactose-free cow's milk, Nonconventional (A2) cow's milk and Nonconventional (A2) lactose-free cow's milk in people with Dairy Intolerance and Healthy Adults, run by Auburn University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gastrointestinal Distress Scores (time frame: 24 hours after each sample challenge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2025.