Milk Oral Immunotherapy in Children to Treat Food Allergy

A Study of the Efficacy of Milk Oral Immunotherapy in Children

Background and Rationale

For patients with Immunoglobulin E (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 Objective

The primary objective is to study the efficacy of milk oral immunotherapy.

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.

Study Overview

• Status: Completed
• Conditions: Milk Hypersensitivity
• Intervention / Treatment: Dietary supplement: Milk Oral Immunotherapy; Drug: Milk Protein Powder; Other: Food Challenge

Detailed Description

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 Measure

The percentage of children completing the desensitization protocol in each study group will be the primary outcome measure.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 kilounits per liter (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 [forced expiratory volume in 1 second (FEV1) < 60% of predicted, as defined by National Heart, Lung, and Blood Institute (NHLBI) 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 double blind placebo controlled food challenge (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Delayed Sensitivity; All subjects will undergo a food challenge (week 2). Subjects undergoing delayed desensitization via milk oral immunotherapy with milk protein powder will begin build-up of desensitization during Week 16 and continue thru Week 50. Total active participation will last 51 weeks.	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.; Other: Food Challenge
Active Comparator: Immediate Sensitivity; All subjects will undergo a food challenge (week 2). Subjects undergoing immediate desensitization via milk oral immunotherapy with milk protein powder will begin build-up of desensitization during Week 3 and continue thru Week 35. Total active participation will last 38 weeks.	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.; Other: Food Challenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Who Completed Desensitization Protocol	Subjects who withdrew prior to completing the desensitization protocol and those who experienced anaphylaxis during the desensitization protocol (i.e., were unable to complete the protocol) were considered to be "treatment failures". Subjects who completed the desensitization protocol were considered to be "treatment successes".	1 year

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Antonella Cianferoni, MD, PhD, Children's Hospital of Philadelphia; Principal Investigator: Jonathan M. Spergel, MD, PhD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• 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. doi: 10.1016/S1081-1206(10)60908-8.
• 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. doi: 10.1016/j.jaci.2008.09.030. 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. doi: 10.1016/j.jaci.2007.10.029. 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. doi: 10.1111/j.1398-9995.2004.00542.x.
• Zapatero L, Alonso E, Fuentes V, Martinez MI. Oral desensitization in children with cow's milk allergy. J Investig Allergol Clin Immunol. 2008;18(5):389-96.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: July 13, 2010
• First Submitted That Met QC Criteria: July 13, 2010
• First Posted (Estimate): July 14, 2010

Study Record Updates

• Last Update Posted (Estimate): May 13, 2015
• Last Update Submitted That Met QC Criteria: May 11, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Food allergy; Milk allergy; Food hypersensitivity; Milk hypersensitivity
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Milk Hypersensitivity; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Caseins
• Other Study ID Numbers: 09-007320