Cow Milk AllergyENIGMANCT05785299
Clinical Versus Home Introduction of Milk in Children with Non-IgE-mediated Cow's Milk Allergy
A study testing Cow's milk and Home introduction in people with Cow Milk Allergy and Food Allergy, run by Martini Hospital Groningen at 1 site in Netherlands.
Trial summary
There are a lot of parents who believe that their child may not tolerate cow's milk because they develop symptoms such as redness of the skin or they may vomit. It is not always easy to find out if these infants should indeed avoid drinking cow's milk or that the symptoms are caused by something else, for instance… Read more about this study
- Who is it for?
- Ages 1 month to 18 months
- Conditions the study is for
- Cow Milk Allergy, Food Allergy
- What is being tested?
- Cow's milk and Home introduction
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteNetherlands
- Study dates
- 9 Oct 2023to 1 Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 1 month to 18 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- maximum age of eighteen months;
- suspected to be allergic for cow's milk (based on medical history);
Who cannot join
- children older than the age of eighteen months;
- sensitised for cow's milk (i.e. SPT >3mm (in combination with positive control ≥3mm) or specific IgE >0.35 kU/L)
- patient suffers from acute (i.e. within one hour after cow's milk had been eaten) and moderate-severe IgE-mediated symptoms after ingestion of cow's milk
- patient suffers from symptoms according to the FPIES criteria after ingestion of cow's milk
- patient uses beta blockers and/or prednisolone;
- patient suffers from uncontrolled respiratory symptoms or severe eczema or a chronic condition because of which the patients cannot be included as judged by the treating physician;
- parents are unable to adequately report the occurrence of possible symptoms (e.g. insufficient language proficiency).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Evaluation of the Outcome of Clinical or Home Introduction of Milk in Children with Non-IgE-mediated Cow's Milk Allergy (ENIGMA Trial)
There are a lot of parents who believe that their child may not tolerate cow's milk because they develop symptoms such as redness of the skin or they may vomit. It is not always easy to find out if these infants should indeed avoid drinking cow's milk or that the symptoms are caused by something else, for instance because they have a viral illness. The goal of the investigators is to find out if cow's milk should be introduced in the hospital or if it can also be advised to perform the introduction at home to determine if an infant can drink cow's milk without developing symptoms. Half of the participants will drink cow's milk in the hospital. This test is performed on two days. On one of the days cow's milk will be offered. On the other day a look-alike substance is offered. The other half of the participants will drink cow's milk at home by starting to drink a little bit of milk and in a few steps drink a normal bottle of cow's milk. The main question is whether both tests can be used to find out if an infant can drink cow's milk without developing symptoms.
Read the detailed description
Cow's milk allergy (CMA) is the most common food allergy among infants. CMA can be divided into immunoglobin E (IgE) and non-IgE-mediated allergy. In case of IgE-mediated allergy, symptoms occur within two hours after ingestion, and are potentially life-threatening. In patients without sensitisation, symptoms may occur up to 48 hours after ingestion and predominantly affect the gastrointestinal tract and skin. The gold standard to diagnose a cow's milk allergy is to perform a double-blind placebo controlled food challenge (DBPCFC). Determination of DBPCFC outcome for non-IgE-mediated allergy can be challenging due to delayed presentation of symptoms after the DBPCFC has been performed. Furthermore, in the majority of infants with non-IgE-mediated cow's milk allergy, symptoms are mild and therefore introduction under medical supervision is superfluous. To date, there is no validated diagnostic to confirm a diagnosis of non-IgE-mediated cow's milk allergy and potential over diagnosis is due to the overlap of symptoms with other common diseases in infants.
The aim of this study is to compare the outcome of an adjusted DBPCFC and introduction at home of cow's milk for children with a suspected non-IgE-mediated cow's milk allergy
Patients with a suspected cow's milk allergy will be randomized to a DBPCFC or home introduction of cow's milk after sensitisation for cow's milk has been excluded and parents have not reported severe symptoms during introduction of cow's milk. Outcome of both introduction methods will be based on predefined criteria. For patients with a negative outcome of the test unrestricted exposure to cow's milk is recommended. In case of a positive outcome, parents are recommended to gradually increase the amount of cow's milk in their child's diet by means of the "milk ladder". During regular follow-up visits the investigators will inquire whether introduction of cow's milk is successful and if needed motivate parents to continue further introduction. Number of all consultations will be registered.
- Conditions
- Cow Milk Allergy, Food Allergy
- Being tested
- Cow's milk, Placebo, Home introduction
- Medical subject headings
- Milk Hypersensitivity, Food Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cow's milkDiagnostic test
Also called Oral food challenge test
clinical introduction of cow's milk
PlaceboDiagnostic test
Also called Oral food challenge test
clinical introduction of placebo
Home introductionDiagnostic test
home introduction of cow's milk
| Study group | Role | What they receive |
|---|---|---|
| Double blind placebo controlled challenge test | Active comparator | Introduction of cow's milk by means of an adjusted double blind placebo controlled challenge test Receives: Diagnostic Test: Cow's milk; Diagnostic Test: Placebo |
| Home introduction test | Active comparator | Introduction of cow's milk by means of a standardized schedule Receives: Diagnostic Test: Home introduction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with a positive or negative test
Positive (intolerant) or negative (tolerant) outcome of the introduction test
Measured: Determined 1 week after start of the test
Secondary outcomes (3)
Regular milk consumption
Milk consumption is based on normal daily intake for age
Measured: Determined 6 weeks after completion of the test
Percentage and type of reported symptoms
Reported symptoms are classified according to predefined criteria
Measured: Determined 6 weeks after completion of the test
Healthcare utilisation during the study period
Healthcare utilisation is determined by evaluation of the number of physical and telephone consultations
Measured: Determined 6 weeks after completion of the test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2023
- Study start9 Oct 2023
- Primary completion1 Jun 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cow Milk AllergyStudies 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
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Martini Hospital Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Kamps, MD, PhD, Principal investigator, Martini Ziekenhuis Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05785299
- Sponsor's protocol ID
- ABR 83741
- Acronym
- ENIGMA
- Status last verified
- Nov 2024
- First submitted
- 24 Feb 2023
- Last updated
- 25 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study protocol and data will be shared upon request
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Outcome of Clinical or Home Introduction of Milk in Children with Non-IgE-mediated Cow's Milk Allergy (ENIGMA Trial)
- ClinicalTrials.gov ID
- NCT05785299
- Acronym / sponsor ID
- ENIGMA / ABR 83741
- Conditions
- Cow Milk Allergy, Food Allergy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Martini Hospital GroningenUniversity, hospital or other
- Study start
- 9 Oct 2023 (actual)
- Primary completion
- 1 Jun 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 27 Mar 2023 (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.
There are a lot of parents who believe that their child may not tolerate cow's milk because they develop symptoms such as redness of the skin or they may vomit. It is not always easy to find out if these infants should indeed avoid drinking cow's milk or that the symptoms are caused by something else, for instance because they have a viral illness. The goal of the investigators is to find out if cow's milk should be introduced in the hospital or if it can also be advised to perform the introduction at home to determine if an infant can drink cow's milk without developing symptoms. Half of the participants will drink cow's milk in the hospital. This test is performed on two days. On one of the days cow's milk will be offered. On the other day a look-alike substance is offered. The other half of the participants will drink cow's milk at home by starting to drink a little bit of milk and in a few steps drink a normal bottle of cow's milk. The main question is whether both tests can be used to find out if an infant can drink cow's milk without developing symptoms.
Detailed description
Cow's milk allergy (CMA) is the most common food allergy among infants. CMA can be divided into immunoglobin E (IgE) and non-IgE-mediated allergy. In case of IgE-mediated allergy, symptoms occur within two hours after ingestion, and are potentially life-threatening. In patients without sensitisation, symptoms may occur up to 48 hours after ingestion and predominantly affect the gastrointestinal tract and skin. The gold standard to diagnose a cow's milk allergy is to perform a double-blind placebo controlled food challenge (DBPCFC). Determination of DBPCFC outcome for non-IgE-mediated allergy can be challenging due to delayed presentation of symptoms after the DBPCFC has been performed. Furthermore, in the majority of infants with non-IgE-mediated cow's milk allergy, symptoms are mild and therefore introduction under medical supervision is superfluous. To date, there is no validated diagnostic to confirm a diagnosis of non-IgE-mediated cow's milk allergy and potential over diagnosis is due to the overlap of symptoms with other common diseases in infants.
The aim of this study is to compare the outcome of an adjusted DBPCFC and introduction at home of cow's milk for children with a suspected non-IgE-mediated cow's milk allergy
Patients with a suspected cow's milk allergy will be randomized to a DBPCFC or home introduction of cow's milk after sensitisation for cow's milk has been excluded and parents have not reported severe symptoms during introduction of cow's milk. Outcome of both introduction methods will be based on predefined criteria. For patients with a negative outcome of the test unrestricted exposure to cow's milk is recommended. In case of a positive outcome, parents are recommended to gradually increase the amount of cow's milk in their child's diet by means of the "milk ladder". During regular follow-up visits the investigators will inquire whether introduction of cow's milk is successful and if needed motivate parents to continue further introduction. Number of all consultations will be registered.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double blind placebo controlled challenge test | Active comparator | Diagnostic Test: Cow's milk, Diagnostic Test: PlaceboIntroduction of cow's milk by means of an adjusted double blind placebo controlled challenge test |
| Home introduction test | Active comparator | Diagnostic Test: Home introductionIntroduction of cow's milk by means of a standardized schedule |
Who may qualify
- Ages
- 1 month to 18 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- maximum age of eighteen months;
- suspected to be allergic for cow's milk (based on medical history);
Key exclusion criteria (7 listed)
- children older than the age of eighteen months;
- sensitised for cow's milk (i.e. SPT >3mm (in combination with positive control ≥3mm) or specific IgE >0.35 kU/L)
- patient suffers from acute (i.e. within one hour after cow's milk had been eaten) and moderate-severe IgE-mediated symptoms after ingestion of cow's milk
- patient suffers from symptoms according to the FPIES criteria after ingestion of cow's milk
- patient uses beta blockers and/or prednisolone;
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 |
|---|---|---|
| Cow's milkAlso: Oral food challenge testclinical introduction of cow's milk | Diagnostic test | Double blind placebo controlled challenge test |
| PlaceboAlso: Oral food challenge testclinical introduction of placebo | Diagnostic test | Double blind placebo controlled challenge test |
| Home introductionhome introduction of cow's milk | Diagnostic test | Home introduction test |
Primary outcome
Number of participants with a positive or negative test
Time frame: Determined 1 week after start of the test
Positive (intolerant) or negative (tolerant) outcome of the introduction test
3 secondary outcomes
Regular milk consumption
Time frame: Determined 6 weeks after completion of the test
Percentage and type of reported symptoms
Time frame: Determined 6 weeks after completion of the test
Healthcare utilisation during the study period
Time frame: Determined 6 weeks after completion of the test
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2024.
- Individual participant dataSharing planned: Yes. Study protocol and data will be shared upon request
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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.
Kamps, MD, PhD principal investigator
Martini Ziekenhuis Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cow's milk and Home introduction in people with Cow Milk Allergy and Food Allergy, run by Martini Hospital Groningen at 1 site in Netherlands.
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 2 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 25 Nov 2024. 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 Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kamps, MD,PhD (31505246900, a.kamps@mzh.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with a positive or negative test (time frame: Determined 1 week after start of the test). 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 25 Nov 2024.