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

• ClinicalTrials.gov Identifier: NCT00465569
• Recruitment Status: Completed
• First Posted: April 25, 2007
• Results First Posted: April 20, 2017
• Last Update Posted: April 20, 2017
• Sponsor: Johns Hopkins University
• Collaborator: Duke University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Milk Hypersensitivity	Drug: cow's milk powder; Other: Placebo	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of Oral Milk Immunotherapy for Cow's Milk Allergy
• Study Start Date: August 2006
• Actual Primary Completion Date: June 2008
• Actual Study Completion Date: June 2008

Arms and Interventions

Arm	Intervention/treatment
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
Placebo Comparator: Placebo	Other: Placebo

Outcome Measures

Primary Outcome Measures :

1. The Median Milk Threshold Dose Inducing a Reaction [ Time Frame: Baseline and 23 weeks ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Maryland

The Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Johns Hopkins University

Duke University

Investigators

• Principal Investigator: Robert A Wood, MD; Johns Hopkins University

More Information

Publications of Results:

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.

Other 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. 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.

Enrique E, Pineda F, Malek T, Bartra J, Basagaña M, Tella R, Castelló JV, Alonso R, de Mateo JA, Cerdá-Trias T, San Miguel-Moncín Mdel M, Monzón S, García M, Palacios R, Cisteró-Bahíma 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. Epub 2005 Oct 3.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00465569
• Other Study ID Numbers: NA_00002102
• First Posted: April 25, 2007
• Results First Posted: April 20, 2017
• Last Update Posted: April 20, 2017
• Last Verified: April 2017

Keywords provided by Johns Hopkins University:

Food Allergy; Oral Immunotherapy; Immunoglobulin E

Additional relevant MeSH terms:

Hypersensitivity; Milk Hypersensitivity; Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate