Food HypersensitivityPhase 2NCT00778258
Study of Milk Allergy and Tolerance in Children
A Phase 2 study testing Baked Milk and Non-baked Milk in people with Food Hypersensitivity and Milk Hypersensitivity, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The purpose of this study is to determine if children who are allergic to milk can increase tolerance through frequent dose-escalation every 6 months versus 12 months leading to eventual tolerance of less heated milk and ultimately unheated milk. Read more about this study
- Who is it for?
- Ages 4 to 10 years
- Conditions the study is for
- Food Hypersensitivity, Milk Hypersensitivity
- What is being tested?
- Baked Milk and Non-baked Milk
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Nov 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 4 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- One or more of the following inclusion criteria for enrollment in the study have to be met:
- Convincing history of an allergic reaction to milk or a positive double blind placebo controlled milk challenge (DBPCMC) within the past 2 years and either detectable milk immunoglobulin E (IgE) or positive prick skin test to milk OR
- Serum milk-IgE of high predictive value >14 kUa/L or prick skin test to milk > 10mm wheal within the past 6 months regardless of past clinical history of reactions OR
- Convincing history of an allergic reaction to milk or a positive DBPCMC more than 2 years ago and either a positive serum milk-IgE < 14 kUA/L or positive prick skin test to milk < 10 mm wheal within the past 6 months (eligible only for the active arm of the study and will undergo a reversed sequence of initial baked-milk challenges)
Who cannot join
- Inability or unwillingness of a participant to give written informed consent or to comply with study protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Mount Sinai School of Medicine
New York, New York, 10029
About this study
Official title: Dietary Intervention in Milk Allergy and Tolerance Development
The purpose of this study is to determine if children who are allergic to milk can increase tolerance through frequent dose-escalation every 6 months versus 12 months leading to eventual tolerance of less heated milk and ultimately unheated milk.
Read the detailed description
Milk is among the most common food allergens in infants and children. The majority of children outgrow their milk allergies; however, the exact mechanisms by which food tolerance is achieved are unknown. Strict avoidance of the offending food is currently the only known therapy. However, some have been known to tolerate milk products cooked at high heat such as when baked in foods.
This clinical trial involves a diet containing extensively baked milk protein to investigate the effects of ingestion of heat-denatured milk on development of oral tolerance to non-baked milk.
- Conditions
- Food Hypersensitivity, Milk Hypersensitivity
- Being tested
- Baked Milk, Non-baked Milk
- Keywords
- Food Allergy, Milk Allergy
- Medical subject headings
- Food Hypersensitivity, Milk Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Baked MilkBiological
At baseline, each subject will undergo sequential oral food challenges with the products that contain increasing amounts of milk protein that are baked: Stage 1 (muffin), Stage 2 (pizza), and Stage 3 (rice pudding) doses of baked milk to determine the extent to which they tolerate various baked milk proteins. Based on the outcomes of the baseline oral food challenges, subjects will be assigned to one of the 5 study arms.
Non-baked MilkBiological
Those subjects tolerant to rice pudding will undergo oral food challenge with non-baked milk.
| Study group | Role | What they receive |
|---|---|---|
| Milk-allergic; Non-consumption | Experimental | Subjects in this arm reacted to the lowest baseline dose of baked milk (muffin) and will continue strict milk avoidance, returning for re-evaluation with laboratory tests at 12 and 24 months and baked milk challenge at 36 months. Individual participants may be challenged at 12 and or 24 months. Receives: Biological: Baked Milk |
| Tolerated Muffin, Reacted to Pizza | Experimental | Subjects will be assigned to this arm, if they can tolerate ingesting a muffin but react to ingesting the amount of baked milk in a standardized portion of pizza. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein. Receives: Biological: Baked Milk |
| Reacted to Rice Pudding | Experimental | Subjects will be assigned to this arm, if they can tolerate ingesting a muffin and a standardized portion of pizza but react to a standardized dose of baked milk in rice pudding. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein. Receives: Biological: Baked Milk |
| Reacted to Non-baked Milk | Experimental | Subjects will be assigned to this arm, if they can tolerate ingesting a muffin, pizza and rice pudding but react to a standardized dose of non-baked milk. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein. Receives: Biological: Baked Milk; Biological: Non-baked Milk |
| Tolerant to Baked and Non-baked Milk | Experimental | Biological/Vaccine: Baked Milk At baseline, each subject will undergo sequential oral food challenges with the products that contain increasing amounts of milk protein that are baked: Stage 1 (muffin), Stage 2 (pizza), and Stage 3 (rice pudding) doses of baked milk to determine the extent to which they tolerate various baked milk proteins. Based on the outcomes of the baseline oral food challenges, subjects will be assigned to one of the 5 study arms.
Biological/Vaccine: Non-baked Milk Those subjects tolerant to rice pudding will undergo oral food challenge with non-baked milk. Receives: Biological: Baked Milk; Biological: Non-baked Milk |
| Non-Interventional Comparison | No intervention | Thirty subjects who fulfill inclusion criteria but are unwilling to participate in the full protocol will be enrolled as a comparison group to the active arms. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Positive Progression in Tolerance of Baked Milk and Ultimately Unheated Milk in Dose Escalation Sub-arm Compared to Maintenance Sub-arm
Participants were grouped based on the food to which they experienced a reaction at the baseline Oral Food Challenge (OFC). Group 1=reacted to muffin; Group 2=reacted to pizza; Group 3=reacted to rice pudding; Group 4=reacted to non-baked milk; Group 5=did not react. Groups 2, 3, and 4 were randomized to dose escalation or maintenance, and at each visit following randomization, participants performed an OFC where they were given food products containing milk protein denatured through baking. Participants were given progressively less denatured milk protein food items until they had an allergic reaction. Participants were considered to have a positive progression in tolerance of baked milk if they experienced a reaction to a less denatured milk protein food item at any post randomization visits than the one to which they reacted at their baseline visit.
Measured: Randomization through end of study (up to 36 months)
Secondary outcomes (11)
Number of Participants With a Positive Progression in Tolerating More Allergenic Forms of Milk at 12 and 24 Months
Participants were grouped based on the food they experienced a reaction to at the baseline Oral Food Challenge (OFC). Group 1 = reacted to muffin; Group 2 = reacted to pizza; Group 3 = reacted to rice pudding; Group 4 = reacted to non-baked milk; Group 5 = did not react. Groups 2, 3 and 4 were randomized to dose escalation or maintenance, and at each visit following randomization, performed an OFC where food products containing milk protein denatured through baking were given. Participants were given progressively less denatured milk protein food items until an allergic reaction occurred. A positive progression in tolerance of baked milk was defined as a reaction to a less denatured milk protein food at 12 months than at baseline. Positive progression at 24 months was defined as experiencing a reaction to a less denatured milk protein food at 24 months than at 12 months.
Measured: 12 months, 24 months
Percent of Participants Becoming Tolerant to Unheated Cow's Milk at 12, 24, and 36 Months
Participants were grouped based on the food to which they experienced a reaction at the baseline Oral Food Challenge (OFC). Group 1 = reacted to muffin; Group 2 = reacted to pizza; Group 3 = reacted to rice pudding; Group 4 = reacted to non-baked milk; Group 5 = did not react. Groups 2, 3 and 4 were randomized to dose escalation or maintenance, and at each visit following randomization, participants performed an OFC where they were given food products containing milk protein denatured through baking. Participants were given progressively less denatured milk protein food items until they had an allergic reaction. Participants were considered to become tolerant to unheated cow's milk if at the specified visit, they did not react to any of the foods given in the OFC.
Measured: 12 months, 24 months, and 36 months
Percent of Participants Becoming Tolerant to Unheated Cow's Milk
Participants were grouped based on the food to which they experienced a reaction at the baseline Oral Food Challenge (OFC). Group 1 = reacted to muffin; Group 2 = reacted to pizza; Group 3 = reacted to rice pudding; Group 4 = reacted to non-baked milk; Group 5 = did not react. Groups 2, 3 and 4 were randomized to dose escalation or maintenance, and at each visit following randomization, participants performed an OFC where they were given food products containing milk protein denatured through baking. Participants were given progressively less denatured milk protein food items until they had an allergic reaction. Participants were considered to become tolerant to unheated cow's milk if at any post-randomization visit up through 36 months, they did not react to any of the food given in the OFC.
Measured: Randomization through end of study (up to 36 months)
Comparison of Baseline Basophil Percent Maximal Degranulation With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
This endpoint evaluates the correlation between the mechanistic biomarkers of basophil reactivity and the food to which participants reacted at baseline. Participants were grouped according to food at which participants experienced a reaction during their baseline oral food challenge: Group 1 = reacted to muffin; Group 2 = reacted to pizza; Group 3 = reacted to rice pudding; Group 4 = reacted to non-baked milk; Group 5 = did not react. Basophils come from blood drawn at baseline. Basophils counts were done using whole blood specimens. Basophil reactivity as measured as maximal degranulation percentage after stimulation with titrated dilutions of milk powder (from 1x103 to 1x10-1 µg/mL total protein) and was correlated to group assignment using Spearman correlation coefficients.
Measured: Baseline
Comparison of Baseline IgE With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
This endpoint evaluates the correlation between the mechanistic biomarker of IgE to milk proteins and allergic reaction at baseline. Participants were grouped according to food at which participants experienced a reaction during their baseline oral food challenge: Group 1 = reacted to muffin; Group 2 = reacted to pizza; Group 3 = reacted to rice pudding; Group 4 = reacted to non-baked milk; Group 5 = did not react. Quantitative IgE to milk proteins was done using FEIA (UniCAP) on serum from blood drawn at baseline.
Measured: Baseline
Comparison of Baseline Mechanistic Studies [Treg and Basophil] With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
This endpoint evaluates the correlation between the mechanistic biomarker of the number of basophils and T regulatory cells reactive to milk proteins and the food to which participants reacted at baseline. Participants were grouped according to food at which participants experienced a reaction during their baseline oral food challenge: Group 1 = reacted to muffin; Group 2 = reacted to pizza; Group 3 = reacted to rice pudding; Group 4 = reacted to non-baked milk; Group 5 = did not react. Quantitative IgE to milk proteins was done using FEIA (UniCAP) on serum from blood drawn at baseline.
Measured: Baseline
Relationship Between Initial Dose of Tolerated Baked-milk Protein and Time to Complete Tolerance
Participants were grouped based on the food to which they experienced a reaction at the baseline Oral Food Challenge (OFC). Group 1 = reacted to muffin; Group 2 = reacted to pizza; Group 3 = reacted to rice pudding; Group 4 = reacted to non-baked milk; Group 5 = did not react. Groups 2, 3 and 4 were randomized to dose escalation or maintenance, and at each visit following randomization, participants performed an OFC where they were given food products containing milk protein denatured through baking. Participants were given progressively less denatured milk protein food items until they had an allergic reaction. Participants were considered to become tolerant to unheated cow's milk if at any post-randomization visit up through 36 months, they did not react to any food, including unheated whole milk.
Measured: Randomization through end of study (up to 36 months)
Relationship Between Dose of Baked-milk Protein and Reactivity to Casein Versus Whey
Participants were grouped based on the food to which they experienced a reaction at the baseline Oral Food Challenge (OFC). Group 1 = reacted to muffin; Group 2 = reacted to pizza; Group 3 = reacted to rice pudding; Group 4 = reacted to non-baked milk; Group 5 = did not react. Groups 2, 3 and 4 were randomized to dose escalation or maintenance, and at each visit following randomization, participants performed an OFC where they were given food products containing milk protein denatured through baking. Participants were given progressively less denatured milk protein food items until they had an allergic reaction. The relationship between serum IgE to betalactoglobulin and casein, and the food level at which the participant reacted, were evaluated at each post randomization OFC visit. It is expected that those who reacted to muffin would have a higher ratio of casein to betalactoglobulin than those who reacted to less heated forms of milk.
Measured: Baseline, Month 12, Month 24, Month 36
Comparison of Percent of Participants Tolerant to Non-heated Milk Between the Participants Who Ingested Baked-milk Products and Participants Who Continued to Avoid All Forms of Milk
Participants were grouped based on the food they reacted to, at the baseline Oral Food Challenge (OFC). Group 1= reacted to muffin; Group 2= reacted to pizza; Group 3= reacted to rice pudding; Group 4= reacted to non-baked milk; Group 5= did not react. Groups 2- 4 were randomized to dose escalation or maintenance, and Group 1, and a Control group that chose not to participate in the study, continued to avoid milk. Randomized participants performed an OFC at each visit during which they were given progressively less denatured/ baked milk protein food items until they had an allergic reaction. Participants were considered tolerant to unheated cow's milk if at any post-randomization visit up through 36 months, they did not react to any food, including unheated whole milk. Tolerance of non-heated milk was assessed by report among those who continued to avoid milk.
Measured: Month 36
Changes in Mechanistic Values [Humoral, T Cell and Basophil]
This outcome measure was not well defined in the protocol and was not analyzed.
Measured: Baseline, Month 12, Month 24, and Month 36
Changes in Mechanistic Values [Humoral, T Cell and Basophil]
This outcome measure was not well defined in the protocol and was not analyzed.
Measured: Baseline to the time complete milk tolerance was established
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2008 (estimated)
- Study startAug 2008
- Primary completionNov 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Food HypersensitivityStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Asthma and Allergic Diseases Cooperative Research Centers
- Responsible party
- Sponsor
- Investigators
- Hugh A. Sampson, MD, Study chair, Icahn School of Medicine at Mount SinaiAnna Nowak-Wegrzyn, MD, Study chair, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00778258
- Sponsor's protocol ID
- DAIT AADCRC-MSSM-02
- Status last verified
- Mar 2016
- First submitted
- 21 Oct 2008
- Last updated
- 30 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Nowak-Wegrzyn A, Bloom KA, Sicherer SH, Shreffler WG, Noone S, Wanich N, Sampson HA. Tolerance to extensively heated milk in children with cow's milk allergy. J Allergy Clin Immunol. 2008 Aug;122(2):342-7, 347.e1-2. doi: 10.1016/j.jaci.2008.05.043. Epub 2008 Jul 11.
PubMed 18620743Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol. 2007 Nov;120(5):1172-7. doi: 10.1016/j.jaci.2007.08.023. Epub 2007 Nov 1.
PubMed 17935766Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007 Nov;62(11):1261-9. doi: 10.1111/j.1398-9995.2007.01501.x.
PubMed 17919140Vandenplas Y, Koletzko S, Isolauri E, Hill D, Oranje AP, Brueton M, Staiano A, Dupont C. Guidelines for the diagnosis and management of cow's milk protein allergy in infants. Arch Dis Child. 2007 Oct;92(10):902-8. doi: 10.1136/adc.2006.110999.
PubMed 17895338
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Intervention in Milk Allergy and Tolerance Development
- ClinicalTrials.gov ID
- NCT00778258
- Acronym / sponsor ID
- DAIT AADCRC-MSSM-02
- Conditions
- Food Hypersensitivity, Milk Hypersensitivity
- Keywords
- Food Allergy, Milk Allergy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 170 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Asthma and Allergic Diseases Cooperative Research Centers
- Study start
- Aug 2008
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 23 Oct 2008 (estimated)
- Results
- Posted 30 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if children who are allergic to milk can increase tolerance through frequent dose-escalation every 6 months versus 12 months leading to eventual tolerance of less heated milk and ultimately unheated milk.
Detailed description
Milk is among the most common food allergens in infants and children. The majority of children outgrow their milk allergies; however, the exact mechanisms by which food tolerance is achieved are unknown. Strict avoidance of the offending food is currently the only known therapy. However, some have been known to tolerate milk products cooked at high heat such as when baked in foods.
This clinical trial involves a diet containing extensively baked milk protein to investigate the effects of ingestion of heat-denatured milk on development of oral tolerance to non-baked milk.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Milk-allergic; Non-consumption | Experimental | Biological: Baked MilkSubjects in this arm reacted to the lowest baseline dose of baked milk (muffin) and will continue strict milk avoidance, returning for re-evaluation with laboratory tests at 12 and 24 months and baked milk challenge at 36 months. Individual participants may be challenged at 12 and or 24 months. |
| Tolerated Muffin, Reacted to Pizza | Experimental | Biological: Baked MilkSubjects will be assigned to this arm, if they can tolerate ingesting a muffin but react to ingesting the amount of baked milk in a standardized portion of pizza. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein. |
| Reacted to Rice Pudding | Experimental | Biological: Baked MilkSubjects will be assigned to this arm, if they can tolerate ingesting a muffin and a standardized portion of pizza but react to a standardized dose of baked milk in rice pudding. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein. |
| Reacted to Non-baked Milk | Experimental | Biological: Baked Milk, Biological: Non-baked MilkSubjects will be assigned to this arm, if they can tolerate ingesting a muffin, pizza and rice pudding but react to a standardized dose of non-baked milk. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein. |
| Tolerant to Baked and Non-baked Milk | Experimental | Biological: Baked Milk, Biological: Non-baked MilkBiological/Vaccine: Baked Milk At baseline, each subject will undergo sequential oral food challenges with the products that contain increasing amounts of milk protein that are baked: Stage 1 (muffin), Stage 2 (pizza), and Stage 3 (rice pudding) doses of baked milk to determine the extent to which they tolerate various baked milk proteins. Based on the outcomes of the baseline oral food challenges, subjects will be assigned to one of the 5 study arms. Biological/Vaccine: Non-baked Milk Those subjects tolerant to rice pudding will undergo oral food challenge with non-baked milk. |
| Non-Interventional Comparison | No intervention | –Thirty subjects who fulfill inclusion criteria but are unwilling to participate in the full protocol will be enrolled as a comparison group to the active arms. |
Who may qualify
- Ages
- 4 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- One or more of the following inclusion criteria for enrollment in the study have to be met:
- Convincing history of an allergic reaction to milk or a positive double blind placebo controlled milk challenge (DBPCMC) within the past 2 years and either detectable milk immunoglobulin E (IgE) or positive prick skin test to milk OR
- Serum milk-IgE of high predictive value >14 kUa/L or prick skin test to milk > 10mm wheal within the past 6 months regardless of past clinical history of reactions OR
- Convincing history of an allergic reaction to milk or a positive DBPCMC more than 2 years ago and either a positive serum milk-IgE < 14 kUA/L or positive prick skin test to milk < 10 mm wheal within the past 6 months (eligible only for the active arm of the study and will undergo a reversed sequence of initial baked-milk challenges)
Key exclusion criteria (1 listed)
- Inability or unwillingness of a participant to give written informed consent or to comply with study protocol
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 |
|---|---|---|
| Baked MilkAt baseline, each subject will undergo sequential oral food challenges with the products that contain increasing amounts of milk protein that are baked: Stage 1 (muffin), Stage 2 (pizza), and Stage 3 (rice pudding) doses of baked milk to determine the extent to which they tolerate various baked milk proteins. Based on the outcomes of the baseline oral food challenges, subjects will be assigned to one of the 5 study arms. | Biological | Milk-allergic; Non-consumption, Reacted to Non-baked Milk, Reacted to Rice Pudding, Tolerant to Baked and Non-baked Milk, Tolerated Muffin, Reacted to Pizza |
| Non-baked MilkThose subjects tolerant to rice pudding will undergo oral food challenge with non-baked milk. | Biological | Reacted to Non-baked Milk, Tolerant to Baked and Non-baked Milk |
Primary outcome
Number of Participants With a Positive Progression in Tolerance of Baked Milk and Ultimately Unheated Milk in Dose Escalation Sub-arm Compared to Maintenance Sub-arm
Time frame: Randomization through end of study (up to 36 months)
Participants were grouped based on the food to which they experienced a reaction at the baseline Oral Food Challenge (OFC). Group 1=reacted to muffin; Group 2=reacted to pizza; Group 3=reacted to rice pudding; Group 4=reacted to non-baked milk; Group 5=did not react. Groups 2, 3, and 4 were randomized to dose escalation or maintenance, and at each visit following randomization, participants performed an OFC where they were given food products containing milk protein denatured through baking. Participants were given progressively less denatured milk protein food items until they had an allergic reaction. Participants were considered to have a positive progression in tolerance of baked milk if they experienced a reaction to a less denatured milk protein food item at any post randomization visits than the one to which they reacted at their baseline visit.
11 secondary outcomes
Number of Participants With a Positive Progression in Tolerating More Allergenic Forms of Milk at 12 and 24 Months
Time frame: 12 months, 24 months
Percent of Participants Becoming Tolerant to Unheated Cow's Milk at 12, 24, and 36 Months
Time frame: 12 months, 24 months, and 36 months
Percent of Participants Becoming Tolerant to Unheated Cow's Milk
Time frame: Randomization through end of study (up to 36 months)
Comparison of Baseline Basophil Percent Maximal Degranulation With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
Time frame: Baseline
Comparison of Baseline IgE With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
Time frame: Baseline
Comparison of Baseline Mechanistic Studies [Treg and Basophil] With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
Time frame: Baseline
Relationship Between Initial Dose of Tolerated Baked-milk Protein and Time to Complete Tolerance
Time frame: Randomization through end of study (up to 36 months)
Relationship Between Dose of Baked-milk Protein and Reactivity to Casein Versus Whey
Time frame: Baseline, Month 12, Month 24, Month 36
Comparison of Percent of Participants Tolerant to Non-heated Milk Between the Participants Who Ingested Baked-milk Products and Participants Who Continued to Avoid All Forms of Milk
Time frame: Month 36
Changes in Mechanistic Values [Humoral, T Cell and Basophil]
Time frame: Baseline, Month 12, Month 24, and Month 36
Changes in Mechanistic Values [Humoral, T Cell and Basophil]
Time frame: Baseline to the time complete milk tolerance was established
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18620743Nowak-Wegrzyn A, Bloom KA, Sicherer SH, Shreffler WG, Noone S, Wanich N, Sampson HA. Tolerance to extensively heated milk in children with cow's milk allergy. J Allergy Clin Immunol. 2008 Aug;122(2):342-7, 347.e1-2. doi: 10.1016/j.jaci.2008.05.043. Epub 2008 Jul 11.
- Background: PubMed 17935766Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol. 2007 Nov;120(5):1172-7. doi: 10.1016/j.jaci.2007.08.023. Epub 2007 Nov 1.
- Background: PubMed 17919140Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007 Nov;62(11):1261-9. doi: 10.1111/j.1398-9995.2007.01501.x.
- Background: PubMed 17895338Vandenplas Y, Koletzko S, Isolauri E, Hill D, Oranje AP, Brueton M, Staiano A, Dupont C. Guidelines for the diagnosis and management of cow's milk protein allergy in infants. Arch Dis Child. 2007 Oct;92(10):902-8. doi: 10.1136/adc.2006.110999.
- Description of NIAID Asthma and Allergic Diseases Cooperative Research Centers (AADCRC) ProgramLink provided by the sponsor.
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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.
Hugh A. Sampson, MD study chair
Icahn School of Medicine at Mount Sinai
Anna Nowak-Wegrzyn, MD study chair
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Baked Milk and Non-baked Milk in people with Food Hypersensitivity and Milk Hypersensitivity, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 4 inclusion and 1 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 30 Mar 2016. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With a Positive Progression in Tolerance of Baked Milk and Ultimately Unheated Milk in Dose Escalation Sub-arm Compared to Maintenance Sub-arm (time frame: Randomization through end of study (up to 36 months)). 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 NCT00778258, which also lists 4 linked publications.
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 30 Mar 2016.