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

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.

Study Overview

• Status: Completed
• Conditions: Milk Allergy
• Intervention / Treatment: Drug: Milk Protein Extract Immunotherapy goal of 4mg/day; Drug: Milk Protein Extract Immunotherapy goal of 7mg/day; Drug: Milk Powder Immunotherapy goal dose 1000mg/day; Drug: Milk Powder Immunotherapy goal dose 2000 mg/day

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • 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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Duke University; Greer Laboratories

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (ACTUAL): June 1, 2010
• Study Completion (ACTUAL): June 1, 2012

Study Registration Dates

• First Submitted: August 8, 2008
• First Submitted That Met QC Criteria: August 11, 2008
• First Posted (ESTIMATE): August 12, 2008

Study Record Updates

• Last Update Posted (ACTUAL): May 15, 2017
• Last Update Submitted That Met QC Criteria: April 6, 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Immunologic Factors; Caseins
• Other Study ID Numbers: NA_00732654