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

• ClinicalTrials.gov Identifier: NCT00732654
• Recruitment Status: Completed
• First Posted: August 12, 2008
• Results First Posted: May 15, 2017
• Last Update Posted: May 15, 2017
• Sponsor: Johns Hopkins University
• Collaborators: Duke University; Greer Laboratories
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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

• 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

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

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

• 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

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

• 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; Immunologic Factors; Caseins; Physiological Effects of Drugs; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action