The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy - Full Text View

Purpose

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	Intervention	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 Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	The Safety and Efficacy of Sublingual/Oral Immunotherapy for the Treatment of Milk Protein Allergy

Resource links provided by NLM:

MedlinePlus related topics: Allergy

U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:

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)
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)
Change in End Point Skin Test [ Time Frame: Change from baseline to after therapy (up to 18 months) ]
Allergen provoked skin test (mm)
Oral Food Challenge Threshold (OFC) Threshold [ Time Frame: Change from baseline to after therapy (up to 18 months) ]
mg CM protein


Enrollment:	30
Study Start Date:	August 2008
Study Completion Date:	June 2012
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Eligibility


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732654

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

Additional Information:

Link to the publication of this research in the Journal of Allergy and Clinical Immunology This link exits the ClinicalTrials.gov site


Responsible Party:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00732654 History of Changes
Other Study ID Numbers:	NA_00732654
Study First Received:	August 8, 2008
Results First Received:	March 28, 2016
Last Updated:	April 6, 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

ClinicalTrials.gov processed this record on June 23, 2017