Study of Milk Allergy and Tolerance in Children

NCT00778258 | Completed Phase 2 Results DMC

• 1 other identifier: DAIT AADCRC-MSSM-02
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Food Hypersensitivity; Milk Hypersensitivity

Keywords

Food Allergy; Milk Allergy

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  12 months, 24 months

• Percent of Participants Becoming Tolerant to Unheated Cow's Milk at 12, 24, and 36 Months

  12 months, 24 months, and 36 months

• Percent of Participants Becoming Tolerant to Unheated Cow's Milk

  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

  Baseline

• Comparison of Baseline IgE With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity

  Baseline

Study Arms (6)

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.

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.

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.

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.

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.

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.

Interventions

Baked Milk BIOLOGICAL

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.

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 Milk BIOLOGICAL

Those subjects tolerant to rice pudding will undergo oral food challenge with non-baked milk.

Reacted to Non-baked Milk; Tolerant to Baked and Non-baked Milk

Eligibility Criteria

• Age: 4 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• Inability or unwillingness of a participant to give written informed consent or to comply with study protocol

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Asthma and Allergic Diseases Cooperative Research Centers: collaborator

Study Sites (1)

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Related Publications (4)

• 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.

  PMID: 18620743 BACKGROUND

• Skripak 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.

  PMID: 17935766 BACKGROUND

• Staden 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.

  PMID: 17919140 BACKGROUND

• Vandenplas 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.

  PMID: 17895338 BACKGROUND

Related Links

• Description of NIAID Asthma and Allergic Diseases Cooperative Research Centers (AADCRC) Program

MeSH Terms

Conditions

Food Hypersensitivity; Milk Hypersensitivity

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Hugh A. Sampson, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Anna Nowak-Wegrzyn, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2008
• First Posted: October 23, 2008
• Study Start: August 1, 2008
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: March 30, 2016
• Results First Posted: March 30, 2016

Record last verified: 2016-03

Locations

US (1)