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

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.

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