Milk IntoleranceNCT05305391
Low-grade Inflammation and Gut Symptoms From A2 and Hydrolyzed A1 Milk
A study testing Dietary intervention in people with Milk Intolerance, run by University of Turku at 1 site in Finland.
Trial summary
The aim of this study is to reveal how different forms of milk casein, lactose and moderate breakdown of proteins affect the symptoms that may arise from milk and markers of inflammation in volunteers receiving symptoms from milk. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Milk Intolerance
- What is being tested?
- Dietary intervention
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteFinland
- Study dates
- 18 May 2022to 3 Mar 2023
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Perceive disturbing gut symptoms from regular milk
- Commits to the research diet for the whole research period
- Age: 18-65
- BMI: 18.5-30
- Healthy (normal kidney, liver and thyroid function and self-reported)
Who cannot join
- Milk allergy
- Regular medication (other than contraceptives) or medication affecting the gut
- Recent course of antibiotics (< 3 months prior the study)
- Pregnancy or lactation
- Diagnosed bowel disease
Trial locations and contacts
1 site in 1 country.
Finland1 site
Food Sciences, Department of Life Technologies, University of Turku
Turku, Turku, 20500
About this study
Official title: Low-grade Inflammation and Gut Symptoms From A2 and Protein-hydrolysed Lactose-free A1 Milk in Lactose-tolerant and Lactose-intolerant Volunteers
The aim of this study is to reveal how different forms of milk casein, lactose and moderate breakdown of proteins affect the symptoms that may arise from milk and markers of inflammation in volunteers receiving symptoms from milk. Research hypotheses are: 1) Protein hydrolyzed milk is as tolerated or better tolerated than A2 milk, and 2) Lactose is the main causative agent of stomach symptoms in milk-sensitive individuals.
- Conditions
- Milk Intolerance
- Being tested
- Dietary intervention
- Medical subject headings
- Lactose Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary interventionOther
The arising gastrointestinal symptoms and inflammation markers from consumption of milk + lactase capsule / placebo.
| Study group | Role | What they receive |
|---|---|---|
| A2 milk + placebo | Experimental | A2 whole milk, 3.5% fat, heat-treated; placebo capsule without enzyme Receives: Other: Dietary intervention |
| A2 milk+ lactase enzyme | Experimental | A2 whole milk, 3.5% fat, heat-treated; lactase capsule Receives: Other: Dietary intervention |
| Protein-hydrolyzed A1 milk + placebo | Experimental | Protein-hydrolyzed lactose-free milk, 3% fat, heat-treated; placebo capsule without enzyme Receives: Other: Dietary intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline in Inflammation marker IL-4
IL-4 (interleukin 4) is measured from fasting plasma samples at the baseline before the study and then after each 3-day study arm on the 4th day. It will be analysed as part of the Olink Target 48 Cytokine Panel (Olink Proteomics, Uppsala, Sweden) that provides absolute quantities for 45 different proteins, such as interleukins, interferons, chemokines and growth factors that are related to inflammation. Differences in plasma inflammation marker is measured as a baseline
Measured: after treatment (4th day)
Secondary outcomes (5)
Changes from Baseline in Inflammation markers
Inflammation markers of 45 different proteins, such as interleukins, interferons, chemokines and growth factors are measured from fasting plasma samples as a baseline before the study and then on the 4th day after each 3-day study arm. The absolute quantities of the markers will be analysed with Olink Target 48 Cytokine Panel (Olink Proteomics, Uppsala, Sweden). Differences in inflammation markers (from plasma)
Measured: after treatment (4th day)
Changes from Baseline in Calprotectin
Faecal calprotectin (from faecal sample) is used to measure inflammation status of the gut. Participants collect the first stool of the day in a collection tube and bring it to the study facility in a cooled bag after each study arm.
Measured: after treatment (4th day)
Changes from Baseline in Stool types and Bowel movements
The changes in bowel movements and stool consistency are recorded using a defecation record with the 7-step Bristol stool chart during the consumption of milks (on each study arm). Participant will record the time of the bowel movement and the dominant type of the stool. The Bristol types will be categorized as hard (types 1 and 2), normal (types 3, 4, and 5), or loose stools (types 6 and 7).
Measured: 3 days during the treatment
Changes from Baseline in Gastrointestinal symptoms
Gastrointestinal symptoms (self-reported) as measured by a questionnaire. The questionnaire is divided into seven types of gastrointestinal discomfort, and also includes a possibility to describe a gastrointestinal discomfort outside these seven given alternatives. The severity of the symptoms is self-reported on a three-step scale. Participants fill the questionnaire during 3 days on the baseline and on each study arm (treatment).
Measured: 3 days during the treatment
Changes from Baseline in high-sensitivity CRP
Inflammation marker high-sensitivity CRP is measured from fasting plasma samples as a baseline before the study and then on the 4th day after each 3-day study arm.
Measured: after treatment (4th day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2022
- Study start18 May 2022
- Primary completion3 Mar 2023
- Study completion3 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Milk 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Turku
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kaisa Linderborg, University of Turku
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05305391
- Sponsor's protocol ID
- MILK3
- Status last verified
- Mar 2023
- First submitted
- 22 Mar 2022
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Sensitive volunteer data may only be shared for collaborative research purposes with a separate agreement with the data owner.
Publications
Mannila E, Hokkanen L, Ahonen E, Turpeinen AM, Kalliomaki M, Kortesniemi M, Linderborg KM. Tolerance of protein-hydrolyzed lactose-free A1 milk and A2 milk in lactose-tolerant and lactose-intolerant volunteers: A randomized crossover trial with 2 parallel groups. J Dairy Sci. 2025 Sep;108(9):9062-9077. doi: 10.3168/jds.2025-26712. Epub 2025 Jul 3.
PubMed 40614809
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-grade Inflammation and Gut Symptoms From A2 and Protein-hydrolysed Lactose-free A1 Milk in Lactose-tolerant and Lactose-intolerant Volunteers
- ClinicalTrials.gov ID
- NCT05305391
- Acronym / sponsor ID
- MILK3
- Conditions
- Milk Intolerance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- University of TurkuUniversity, hospital or other
- Study start
- 18 May 2022 (actual)
- Primary completion
- 3 Mar 2023 (actual)
- Study completion
- 3 Mar 2023 (actual)
- First posted
- 31 Mar 2022 (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 aim of this study is to reveal how different forms of milk casein, lactose and moderate breakdown of proteins affect the symptoms that may arise from milk and markers of inflammation in volunteers receiving symptoms from milk. Research hypotheses are: 1) Protein hydrolyzed milk is as tolerated or better tolerated than A2 milk, and 2) Lactose is the main causative agent of stomach symptoms in milk-sensitive individuals.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| A2 milk + placebo | Experimental | Other: Dietary interventionA2 whole milk, 3.5% fat, heat-treated; placebo capsule without enzyme |
| A2 milk+ lactase enzyme | Experimental | Other: Dietary interventionA2 whole milk, 3.5% fat, heat-treated; lactase capsule |
| Protein-hydrolyzed A1 milk + placebo | Experimental | Other: Dietary interventionProtein-hydrolyzed lactose-free milk, 3% fat, heat-treated; placebo capsule without enzyme |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Perceive disturbing gut symptoms from regular milk
- Commits to the research diet for the whole research period
- Age: 18-65
- BMI: 18.5-30
- Healthy (normal kidney, liver and thyroid function and self-reported)
Key exclusion criteria (5 listed)
- Milk allergy
- Regular medication (other than contraceptives) or medication affecting the gut
- Recent course of antibiotics (< 3 months prior the study)
- Pregnancy or lactation
- Diagnosed bowel disease
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 |
|---|---|---|
| Dietary interventionThe arising gastrointestinal symptoms and inflammation markers from consumption of milk + lactase capsule / placebo. | Other | A2 milk + placebo, A2 milk+ lactase enzyme, Protein-hydrolyzed A1 milk + placebo |
Primary outcome
Changes from baseline in Inflammation marker IL-4
Time frame: after treatment (4th day)
IL-4 (interleukin 4) is measured from fasting plasma samples at the baseline before the study and then after each 3-day study arm on the 4th day. It will be analysed as part of the Olink Target 48 Cytokine Panel (Olink Proteomics, Uppsala, Sweden) that provides absolute quantities for 45 different proteins, such as interleukins, interferons, chemokines and growth factors that are related to inflammation. Differences in plasma inflammation marker is measured as a baseline
5 secondary outcomes
Changes from Baseline in Inflammation markers
Time frame: after treatment (4th day)
Changes from Baseline in Calprotectin
Time frame: after treatment (4th day)
Changes from Baseline in Stool types and Bowel movements
Time frame: 3 days during the treatment
Changes from Baseline in Gastrointestinal symptoms
Time frame: 3 days during the treatment
Changes from Baseline in high-sensitivity CRP
Time frame: after treatment (4th day)
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 29 Apr 2026.
- Results publication: PubMed 40614809Mannila E, Hokkanen L, Ahonen E, Turpeinen AM, Kalliomaki M, Kortesniemi M, Linderborg KM. Tolerance of protein-hydrolyzed lactose-free A1 milk and A2 milk in lactose-tolerant and lactose-intolerant volunteers: A randomized crossover trial with 2 parallel groups. J Dairy Sci. 2025 Sep;108(9):9062-9077. doi: 10.3168/jds.2025-26712. Epub 2025 Jul 3.
- Individual participant dataSharing planned: No. Sensitive volunteer data may only be shared for collaborative research purposes with a separate agreement with the data owner.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary intervention in people with Milk Intolerance, run by University of Turku at 1 site in Finland.
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 5 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 29 Apr 2026. 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 Finland. 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?
Changes from baseline in Inflammation marker IL-4 (time frame: after treatment (4th day)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05305391, which also lists 1 linked publication.
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 29 Apr 2026.