An Interventional Study of Milk Allergy and Tolerance in Children - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00778258

Purpose

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. 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.

Condition	Intervention	Phase
Food Hypersensitivity Milk Hypersensitivity	Dietary Supplement: Oral Food Challenge	Phase 0

Study Type:	Interventional
Study Design:	Diagnostic, Non-Randomized, Open Label, Parallel Assignment
Official Title:	Dietary Intervention in Milk Allergy and Tolerance Development

Resource links provided by NLM:

MedlinePlus related topics: Allergy Diets Food Allergy

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Ratio for progression in tolerance of baked milk and ultimately unheated milk in Dose escalation sub-arm compared to Maintenance sub-arm 2 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Odds ratio for progression in tolerating more allergenic forms of milk [ Time Frame: At Months 12 and 24 ] [ Designated as safety issue: No ]
Percent of participants becoming tolerant to unheated cow's milk [ Time Frame: At Months 12, 24, and 36 ] [ Designated as safety issue: No ]
Percent of participants who develop tolerance to unheated cow's milk [ Time Frame: Through 36 Months ] [ Designated as safety issue: No ]
Correlation of baseline mechanistic studies [humoral, T cell and basophil] and stool CD23 and IgE with the outcome of the baseline OFC to identify the biomarkers of clinical reactivity and persistence of milk allergy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Relationship between initial dose of tolerated baked-milk protein and time to complete tolerance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Relationship between reactivity to casein versus whey fractions and time to complete tolerance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Relationship between dose of baked-milk protein and reactivity to casein versus whey and type of symptoms elicited during OFC [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Comparison of percent of participants tolerant to non-heated milk protein between the participants in Arms 1 and 2 [ Time Frame: At Months 12, 24, and 36 ] [ Designated as safety issue: No ]
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: Throughout the study ] [ Designated as safety issue: No ]

Estimated Enrollment:	180
Study Start Date:	August 2008
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will be assigned to one of five subgroups based on baseline tolerance to milk products with varying oral food challenges and evaluations	Dietary Supplement: Oral Food Challenge Consumable products consisting of baked and non-baked milk products
2: Active Comparator Participants will avoid milk consumption and be offered the option to undergo periodic oral food challenges to milk	Dietary Supplement: Oral Food Challenge Consumable products consisting of baked and non-baked milk products

Detailed Description:

In the United States, as many as 8% of children less than three years of age are affected by food hypersensitivity. Milk is among the most common food allergens in infants and children. Although strict avoidance of milk is the current standard of care for those with milk hypersensitivity, there are data that suggest that the majority of children allergic to milk will tolerate heated milk products. Preliminary findings suggest that tolerance may be induced more quickly in those participants who ingest extensively heated, baked milk products. Therefore, a more rapid introduction of increasing doses of baked milk protein into the diet may result in accelerated development of tolerance to unheated milk. The purpose of this study is to determine whether more rapid introduction of increasingly allergenic forms of baked-milk products in baked-milk non-reactive participants shortens the time until they tolerate higher doses of less heated milk and ultimately unheated milk.

The study will last up to 46 months for each study participant. There will be two Arms: Active Treatment Arm 1 and Comparison Arm 2. At study entry, all participants in Arm 1 will undergo sequential oral food challenges (OFCs) that contain increasing amounts of baked milk protein to determine the extent to which they tolerate various baked milk proteins. The participants tolerating baked milk will then be randomly assigned to one of two sub-arms that will receive treatment with various baked milk products.

Group 1 participants who react to baked milk will continue strict milk avoidance and return for re-evaluation with baked milk challenge every 12 months until Month 36. Participants in Groups 2, 3, and 4 are tolerant to different forms of baked milk and will be randomized to return for re-evaluation every 6 or 12 months for dose escalation. In Arm 1, a review of clinical reactions, OFC, prick skin test, quality of life assessment, anthropometric measurements, mechanistic studies, and stool sample collection will occur at all study visits.

Arm 2, the comparison group, will consist of participants who fulfill inclusion criteria, but have elected not to participate in the ingestion of baked milk products. Study visits will occur at months 12, 24, and 36. A review of clinical reactions, prick skin test, quality of life assessment, mechanistic studies, and stool sample collection will occur at all study visits. OFCs are optional for participants in Arm 2.

Eligibility

Ages Eligible for Study:	4 Years to 10 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Suspected allergy to cow's milk
History of non-life threatening allergic reaction to milk or positive DBPCMC within 2 years prior to study entry or serum milk-IgE of high predictive value or milk prick skin test wheal of at least 10 mm within 6 months prior to study entry

Exclusion Criteria:

Serum cow's milk specific IgE antibody greater than 35 kUA/L
History of life-threatening (grade 4) anaphylactic reaction to milk within 2 years prior to study entry
Unstable atopic disease such as asthma, atopic dermatitis, or allergic rhinitis within 7 days prior to study entry
Gastrointestinal eosinophilic disorders caused by milk
Use of short-acting antihistamines more than one time within 3 days prior to study entry
Use of medium-acting antihistamines more than one time within 7 days prior to study entry
Use of systemic steroids within 14 days prior to study entry
Maintenance therapy or use of beta-blockers and ACE inhibitors within 12-24 hours prior to study entry
Participation in any other trials of therapeutic interventions for food allergy
Therapy with anti-IgE for asthma within 1 year prior to study entry
Mental illness that, in the opinion of the investigator, would interfere with the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00778258

Locations

United States, New York
Mount Sinai School of Medicine	Recruiting
New York, New York, United States, 10029
Contact: Beth Robinson, RN 212-241-0957 Beth.robinson@mssm.edu
Principal Investigator: Hugh A. Sampson, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Hugh A. Sampson, MD	Mount Sinai School of Medicine
Study Chair:	Anna Nowak-Wegrzyn, MD	Mount Sinai School of Medicine

More Information

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. Epub 2008 Jul 11.

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. Epub 2007 Nov 1.

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.

Vandenplas Y, Brueton M, Dupont C, Hill D, Isolauri E, Koletzko S, Oranje AP, Staiano A. Guidelines for the diagnosis and management of cow's milk protein allergy in infants. Arch Dis Child. 2007 Oct;92(10):902-8. Review. Erratum in: Arch Dis Child. 2007 Oct;92(10):following 908.

Responsible Party:	DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers:	DAIT AADCRC-MSSM-02, DAIT 07-0563
Study First Received:	October 21, 2008
Last Updated:	June 16, 2009
ClinicalTrials.gov Identifier:	NCT00778258 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Food Allergy
Milk Allergy

Additional relevant MeSH terms:

Hypersensitivity, Immediate
Immune System Diseases
Hypersensitivity
Milk Hypersensitivity
Food Hypersensitivity

ClinicalTrials.gov processed this record on November 20, 2009