The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy

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

Official Title
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The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy

Conditions
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Milk Allergy

Intervention / Treatment
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* Drug: Milk Protein Extract Immunotherapy goal of 4mg/day
* Drug: Milk Protein Extract Immunotherapy goal of 7mg/day
* Drug: Milk Powder Immunotherapy goal dose 2000 mg/day
* Drug: Milk Powder Immunotherapy goal dose 1000mg/day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are age 6 to 21 years Provide signed informed consent (by parent or legal guardian if the subject is a minor), and informed assent if applicable Have a history of symptomatic reactivity to cow's milk (i.e. Eczema, urticaria, upper or lower respiratory symptoms, GI disturbances, other rash or oral symptoms) Have a positive skin prick test (defined as wheal 3 mm ≥ negative control) and cow's milk- immunoglobulin E (IgE) > 0.35 kilo Immunoglobulin Units (kIU)/L Have a positive OFC to cow's milk at a cumulative dose of less than 184 milligrams of cow's milk intact protein (2,400 mg total milk protein). Are using appropriate birth control if subject is female and of child bearing age. Have self-injectable epinephrine (ie. EpiPen® or EpiPen Jr.®) available at home Exclusion Criteria: Have a history of severe anaphylaxis defined as hypoxia (cyanosis or SpO2 ≤ 92% at any stage), hypotension, confusion, collapse, loss of consciousness; or incontinence Have a history of intubation related to asthma Tolerate more than 184 milligrams of intact cow's milk protein at initial OFC Are pregnant or lactating Have a viral Upper Respiratory Infection (URI) or gastroenteritis within 7 days of OFC (OFC needs to be rescheduled) Have pulmonary function tests <80% of predicted (FEV1) or clinical history consistent with more than moderate persistent asthma Are currently taking greater than medium dose inhaled corticosteroid (>400 mcg/day fluticasone or fluticasone equivalent if ≤ 12 years old or > 600 mcg/day if > 12 years old) Are unable to discontinue antihistamines for 5 days for long acting and 3 days for short acting prior to skin testing or food challenges Have used systemic corticosteroids within 4 weeks prior to baseline visit Are receiving omalizumab, beta-blocker, Angiotensin Converting Enzyome (ACE) inhibitor or tricyclic antidepressant therapy Have a chronic disease (other than asthma, atopic dermatitis or rhinitis) requiring therapy (e.g., heart disease, diabetes) Have participated in any interventional study for treatment of a food allergy in the past 12 months Have a severe reaction at initial DBPCFC, defined as either: Life-threatening anaphylaxis, or Reaction requiring hospitalization

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sublingual Immunotherapy (SLIT)<br>These subjects will have a dose escalation of the milk protein extract given sublingually. After dose escalation, they will continue on the sublingual daily maintenance dose for approximately one year. Milk Protein Extract Immunotherapy : Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years. | Drug: Milk Protein Extract Immunotherapy goal of 4mg/day<br>* Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.<br>Drug: Milk Protein Extract Immunotherapy goal of 7mg/day<br>* Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.<br>|
| Experimental: SLIT/ Oral Immunotherpay (OIT) B<br>These subjects will start with a dose escalation of the milk protein extract given sublingually, and then will switch to milk powder given orally and will undergo a dose escalation for a goal of 1000 mg. After dose escalation, they will continue on the oral daily maintenance dose for approximately one year. Milk Powder Immunotherapy : Milk powder given orally in escalating doses with a goal of 1000mg/day for approximately 1 1/2 years. | Drug: Milk Protein Extract Immunotherapy goal of 4mg/day<br>* Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.<br>Drug: Milk Powder Immunotherapy goal dose 1000mg/day<br>* Milk powder given orally in escalating doses with a goal of 1000mg/day for approximately 1 1/2 years.<br>|
| Experimental: SLIT/ OIT A<br>These subjects will start with a dose escalation of the milk protein extract given sublingually, and then will switch to milk powder given orally and will undergo a dose escalation for a goal of 2000 mg. After dose escalation, they will continue on the oral daily maintenance dose for approximately one year. Milk Powder Immunotherapy : Milk powder given orally in escalating doses with a goal dose of 2000mg/day given for approximately 1 1/2 years. Milk Protein Extract Immunotherapy : Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks. | Drug: Milk Protein Extract Immunotherapy goal of 4mg/day<br>* Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks.<br>Drug: Milk Powder Immunotherapy goal dose 2000 mg/day<br>* Milk powder given orally in escalating doses with a goal dose of 2000mg/day given for approximately 1 1/2 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CM-specific Immunogloblin E (IgE) | Cow's milk specific IgE was measured at baseline and after therapy (kUa/L) | Change from baseline to after therapy (up to 18 months) | 
| Change in CM-specific Immunoglobulin G4 (IgG4) | Cow's milk specific IgG4 was measured at baseline and after therapy (kUa/L) | Change from baseline to after therapy (up to 18 months) | 
| Change in End Point Skin Test | Allergen provoked skin test (mm) | Change from baseline to after therapy (up to 18 months) | 
| Oral Food Challenge Threshold (OFC) Threshold | mg CM protein | Change from baseline to after therapy (up to 18 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food Allergy, Oral Immunotherapy, Immunoglobulin E