Milk Oral Immunotherapy in Children

• A secondary outcome measure is the comparison of specific IgE values for milk between the beginning and end of the desensitization protocol. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Another secondary outcome measure includes the comparison of quality of life before and after desensitization. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Another secondary outcome measure includes the comparison of skin prick test for milk extract size before and after desensitization [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Another secondary outcome measure includes the percent change in invariant NKT cells and their cytokine expression between the immediate and delayed desensitization groups. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Background and Rationale

For patients with IgE-mediated food allergy, the current management includes identification of the causative food and avoidance. Specifically, among young children, cow's milk allergy is the most common food allergy, occurring in as many as 2-3%. Given the prevalence of milk and the difficulty to avoid it in the diet, the investigators aim to investigate the safety and efficacy of oral immunotherapy for cow's milk allergy.

Main Objectives

The primary objective is to study the efficacy of milk oral immunotherapy. The secondary objectives are to determine the safety of allergen-specific immunotherapy for milk allergy and whether it will lead to a desensitized or tolerized state. The investigators will also examine if quality of life is improved by expansion of diets and will study the peripheral biomarkers and immune response of children with food allergy.

Target Population

Children aged six to 17 years with a history of cow's milk allergy will be recruited from The Children's Hospital of Philadelphia Allergy clinical offices for the investigators study.

Primary Study Interventions

Prior to and after the desensitization, we will conduct double-blind placebo controlled food challenges to cow's milk protein. During the desensitization phase, we will give increasing doses of cow's milk protein by mouth on a weekly basis, as tolerated. The desensitization protocol starts with dilutional doses of milk and build up to a goal of 8 ounces of cow's milk.

Main Study Outcome Measures

The percentage of children completing the desensitization protocol in each study group will be the primary outcome measure. Secondary outcome measures include milk-specific IgE, quality of life before and after desensitization, milk extract skin prick test size, and the percent change in iNKT cells and their cytokine expression between the immediate and delayed desensitization groups.

• Behavioral: Quality of Life Survey

  A quality of life questionnaire will be given to the subject and his or her family for voluntary completion. The same questionnaire will be given to the subject and his or her family for voluntary completion at the end of the study.

  Through the use of the quality of life questionnaires, we will determine the impact of food allergy on the activities of daily life in food allergic subjects and their families.

  Our secondary endpoint in this study evaluates whether there is an impact on the quality of life after completion of the desensitization and introduction of milk into the subject's diet.

• Dietary Supplement: Milk Oral Immunotherapy
  Subjects will participate in a desensitization protocol over the course of 13 weeks to reach a goal maintenance dose of 8 ounces of cow's milk. Once reaching maintenance, subjects will continue on this dose for 12 additional weeks.
• Drug: Milk Protein Powder
  Milk protein powder will be administered in incremental doses during the desensitization protocol.

• Bollinger ME, Dahlquist LM, Mudd K, Sonntag C, Dillinger L, McKenna K. The impact of food allergy on the daily activities of children and their families. Ann Allergy Asthma Immunol. 2006 Mar;96(3):415-21.
• Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, Matsui EC, Burks AW, Wood RA. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008 Dec;122(6):1154-60. Epub 2008 Oct 25.
• Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol. 2008 Feb;121(2):343-7. Epub 2007 Dec 26.
• Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG. A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy. 2004 Sep;59(9):980-7.
• Zapatero L, Alonso E, Fuentes V, Martínez MI. Oral desensitization in children with cow's milk allergy. J Investig Allergol Clin Immunol. 2008;18(5):389-96.

Inclusion Criteria:

1. Subjects must be age six to 17 years and have a history of cow's milk allergy. Subjects shall maintain strict avoidance of consumption of all cow's milk protein containing foods.
2. Subjects will have a history (within the past six months) of a positive skin prick test to milk extract or an immunocap IgE level greater than 0.35 kU/L, and a positive allergic reaction history to milk within the past 12 months.
3. Subjects must be in good health, as determined by medical history and physical examination performed by a study physician.
4. Females of childbearing potential must be using an effective method of contraception, including abstinence, and agree to continue to practice an acceptable method of contraception for the duration of their participation in the study.
5. Informed consent of parent or legal guardian is required.

Exclusion Criteria:

1. Ability to tolerate eight ounces of cow's milk or eight grams of milk protein powder
2. Pregnancy
3. A history of soy allergy
4. A history of food protein induced enterocolitis syndrome to milk
5. A history of anaphylaxis requiring hospitalization
6. A history of intubation related to asthma and/or a history of an intensive care unit admission for asthma management
7. A current diagnosis of severe persistent asthma [FEV1 (forced expiratory volume in 1 second) < 60% of predicted, as defined by NHLBI (National Heart, Lung, and Blood Institute) guidelines, despite current therapy]
8. A current diagnosis of severe atopic dermatitis
9. A serious chronic medical condition, including neurologic, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, or metabolic disease
10. Use of oral or injection steroids within one month of protocol initial visit
11. An acute illness within one week prior to the first dose of oral immunotherapy
12. Use of antihistamines within seven days prior to DBPCFC
13. Use of chronic immunomodulatory therapy
14. Participation in another experimental therapy study
15. Participation in a study for the treatment of food allergy in the past 12 months
16. Inability to discontinue antihistamines for skin testing and food challenges