Milk Oral Immunotherapy in Children to Treat Food Allergy

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Completed
• CT.gov ID: NCT01162473
• Collaborator: (none)
• Enrollment: 25
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Milk Hypersensitivity	Dietary Supplement: Milk Oral Immunotherapy; Drug: Milk Protein Powder; Other: Food Challenge	Early Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Study of the Efficacy of Milk Oral Immunotherapy in Children
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Who Completed Desensitization Protocol [1 year]

   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".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

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.
• 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.
• 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.
• 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.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT01162473
• Other Study ID Numbers: 09-007320
• First Posted: Jul 14, 2010
• Last Update Posted: May 13, 2015
• Last Verified: May 1, 2015

• Keywords provided by Children's Hospital of Philadelphia: Food hypersensitivity; Milk hypersensitivity; Milk allergy; Food allergy
• Additional relevant MeSH terms: Hypersensitivity; Milk Hypersensitivity; Caseins

Study Results

Participant Flow

Recruitment Details	Children with a history of cow's milk allergy were referred from CHOP Allergy Clinics located in the main campus and satellite offices. Allergy and general pediatric practices in the greater Philadelphia area were also contacted by study staff as part of enrollment outreach.

Arm/Group Title	Delayed Sensitivity	Immediate Sensitivity
Arm/Group Description	All subjects underwent a food challenge (week 2). Subjects undergoing delayed desensitization via milk oral immunotherapy with milk protein powder began build-up of desensitization during Week 16 and continued thru Week 50. Total active participation lasted 51 weeks.	All subjects underwent a food challenge (week 2). Subjects undergoing immediate desensitization via milk oral immunotherapy with milk protein powder began build-up of desensitization during Week 3 and continued thru Week 35. Total active participation lasted 38 weeks.
Period Title: Overall Study
STARTED	8	17
COMPLETED	6	12
NOT COMPLETED	2	5

Baseline Characteristics

Arm/Group Title	Delayed Sensitivity	Immediate Sensitivity	Total
Arm/Group Description	All subjects underwent a food challenge (week 2). Subjects undergoing delayed desensitization via milk oral immunotherapy with milk protein powder began build-up of desensitization during Week 16 and continued thru Week 50. Total active participation lasted 51 weeks.	All subjects underwent a food challenge (week 2). Subjects undergoing immediate desensitization via milk oral immunotherapy with milk protein powder began build-up of desensitization during Week 3 and continued thru Week 35. Total active participation lasted 38 weeks.	Total of all reporting groups
Overall Participants	8	17	25
Age (Count of Participants)
<=18 years	8 100%	17 100%	25 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	8.25	8.88	8.68
Sex: Female, Male (Count of Participants)
Female	3 37.5%	6 35.3%	9 36%
Male	5 62.5%	11 64.7%	16 64%
Region of Enrollment (participants) [Number]
United States	8 100%	17 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Who Completed Desensitization Protocol
Description	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".
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The analysis population included all subjects who began desensitization per protocol.

Arm/Group Title	Delayed Sensitivity	Immediate Sensitivity
Arm/Group Description	All subjects underwent a food challenge (week 2). Subjects undergoing delayed desensitization via milk oral immunotherapy with milk protein powder began build-up of desensitization during Week 16 and continued thru Week 50. Total active participation lasted 51 weeks.	All subjects underwent a food challenge (week 2). Subjects undergoing immediate desensitization via milk oral immunotherapy with milk protein powder began build-up of desensitization during Week 3 and continued thru Week 35. Total active participation lasted 38 weeks.
Measure Participants	8	17
Number [participants]	6 75%	12 70.6%

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Safety was assessed at all follow-up clinic visits. Adverse events encountered during the previous week, as documented on subjects' event journals, were reviewed. Full physical exams performed and vital signs were obtained. During desensitization, families were contacted every other day (first week) and then twice a week (weeks 2-6).
Arm/Group Title	Delayed Desensitization		Immediate Desensitization
Arm/Group Description	Subjects undergoing delayed desensitization via milk oral immunotherapy with milk protein powder (42 week protocol).		Subjects undergoing immediate desensitization via milk oral immunotherapy with milk protein powder (29 week protocol)
All Cause Mortality
	Delayed Desensitization		Immediate Desensitization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Delayed Desensitization		Immediate Desensitization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25%)		1/17 (5.9%)
Immune system disorders
Anaphylaxis	2/8 (25%)	2	1/17 (5.9%)	1
Other (Not Including Serious) Adverse Events
	Delayed Desensitization		Immediate Desensitization
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		4/17 (23.5%)
Gastrointestinal disorders
Abdominal Pain	1/8 (12.5%)	1	4/17 (23.5%)	4

Limitations/Caveats

The small sample size constrains the statistical significance of this study. While useful in indicating potential trends, the results of this pilot study should be cautiously interpreted.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.