A Randomized, Double-Blind, Placebo-Controlled Study of Oral Milk Immunotherapy for Cow's Milk Allergy

The purpose of this study is to determine if small oral doses of milk protein are safe and effective in decreasing sensitivity to cow's milk in allergic children.

Study Overview

• Status: Completed
• Conditions: Milk Hypersensitivity
• Intervention / Treatment: Other: Placebo; Drug: cow's milk powder

Detailed Description

This is a prospective, multi-center, clinical trial involving children aged 6 to 21 years with persistent cow's milk allergy. These children will be recruited from 2 sites (Johns Hopkins and Duke University) and will undergo initial screening and double-blind, placebo-controlled, food challenge (DBPCFC) to confirm threshold dose for reactivity to milk. Patients will be treated with milk oral immunotherapy (OIT) or placebo for 22-30 weeks. Those who reach an adequate maintenance dose for OIT will undergo a second DBPCFC. Those who develop desensitization will continue with daily milk intake and undergo a third DBPCFC. Those in the treatment group who are not desensitized will return to strict avoidance. Those in placebo group will be offered to begin treatment or continue with strict milk avoidance. Symptom and diet information will be collected initially and at regular intervals. Bloodwork, skin prick tests (SPTs), pulmonary function tests (PFTs), and oral secretion samples will be done initially and at periodic intervals.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provide signed informed consent (by parent or legal guardian if the subject is a minor) and informed assent if applicable
• Age 6 to 21 years
• Must have history of symptomatic reactivity to cow's milk (eczema, urticaria, upper/lower resp., GI, other associated rash, oral symptoms)
• History of positive skin prick test (wheal >/= histamine control) or milk-Immunoglobulin E (IgE)>0.35 kilounits per liter (kU/L)
• Positive DBPCFC
• All females of child bearing age must be using appropriate birth control

Exclusion Criteria:

• History of anaphylaxis requiring hospitalization
• History of intubation related to asthma
• Has the ability to tolerate >2.4gram of milk protein at initial DBPCFC
• Has a history of allergy to any component of vehicle
• Pregnancy (need negative test)
• Viral upper respiratory infection (URI) or gastroenteritis within 7days of OFC (OFC needs to be rescheduled)
• Has pulmonary function tests <80% of predicted (FEV1) or clinical history consistent with moderate persistent asthma
• Currently taking greater than medium dose inhaled corticosteroid (>400mcg/day fluticasone or fluticasone equivalent if </=12yo or >600mcg/day if >12 years old)
• Antihistamine within 1 week prior to skin testing or food challenges (Skin testing and/or food challenge needs to be rescheduled)
• Systemic corticosteroid within 4 weeks prior to baseline visit
• Receiving omalizumab, beta-blocker, Angiotensin-converting enzyme (ACE) inhibitor or tricyclic antidepressant therapy
• Chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy (e.g., heart disease, diabetes)
• Participation in any interventional study for treatment of a food allergy in the past 12 months

• Severe reaction at initial DBPCFC, defined as:

  i. Life-threatening anaphylaxis ii. Requires overnight hospitalization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Other: Placebo
EXPERIMENTAL: Active Treatment; Pre-measured doses of dry, nonfat powered milk prepared by the clinical research-registered dieticians	Drug: cow's milk powder; Milk powder given orally in escalating doses to a goal of 500 mg for approximately 23 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Median Milk Threshold Dose Inducing a Reaction	Baseline and 23 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Cow Milk-IgE	IgE is measured in kilounits per liter (kU/L). Measurements were obtained at Baseline and at 23 weeks	Baseline and 23 weeks
Changes in Cow Milk Immunoglobulin G4 (IgG4)	IgG4 is measured in ug/mL. Measurements were obtained at Baseline and at 23 weeks	Baseline and 23 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Duke University

Publications and helpful links

General Publications

• Buchanan AD, Green TD, Jones SM, Scurlock AM, Christie L, Althage KA, Steele PH, Pons L, Helm RM, Lee LA, Burks AW. Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol. 2007 Jan;119(1):199-205. doi: 10.1016/j.jaci.2006.09.016. Epub 2006 Oct 27.
• 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.
• Enrique E, Pineda F, Malek T, Bartra J, Basagana M, Tella R, Castello JV, Alonso R, de Mateo JA, Cerda-Trias T, San Miguel-Moncin Mdel M, Monzon S, Garcia M, Palacios R, Cistero-Bahima A. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005 Nov;116(5):1073-9. doi: 10.1016/j.jaci.2005.08.027. Epub 2005 Oct 3.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (ACTUAL): June 1, 2008
• Study Completion (ACTUAL): June 1, 2008

Study Registration Dates

• First Submitted: April 23, 2007
• First Submitted That Met QC Criteria: April 23, 2007
• First Posted (ESTIMATE): April 25, 2007

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Food Allergy; Oral Immunotherapy; Immunoglobulin E
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Milk Hypersensitivity
• Other Study ID Numbers: NA_00002102