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

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Milk Allergy	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	Phase 1; Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	30 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy
Study Start Date :	August 2008
Actual Primary Completion Date :	June 2010
Actual Study Completion Date :	June 2012

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Sublingual Immunotherapy (SLIT); 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; Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks. Drug: Milk Protein Extract Immunotherapy goal of 7mg/day; Sublingual extract daily in escalating doses to goal of 7mg/day for approximately 1 1/2 years.
Experimental: SLIT/ Oral Immunotherpay (OIT) B; 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; Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks. Drug: Milk Powder Immunotherapy goal dose 1000mg/day; Milk powder given orally in escalating doses with a goal of 1000mg/day for approximately 1 1/2 years.
Experimental: SLIT/ OIT A; 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; Sublingual extract given daily in escalating doses with goal of 4 mg/day for approximately 20 weeks. Drug: Milk Powder Immunotherapy goal dose 2000 mg/day; Milk powder given orally in escalating doses with a goal dose of 2000mg/day given for approximately 1 1/2 years.

Outcome Measures

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Primary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Maryland
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

Greer Laboratories

Investigators

Principal Investigator:	Robert Wood, MD	Johns Hopkins University

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Link to the publication of this research in the Journal of Allergy and Clinical Immunology 

Responsible Party:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00732654 History of Changes
Other Study ID Numbers:	NA_00732654
First Posted:	August 12, 2008
Results First Posted:	May 15, 2017
Last Update Posted:	May 15, 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