Clinical trial NCT00465569: A Randomized, Double-Blind, Placebo-Controlled Study of Oral Milk Immunotherapy for Cow's Milk Allergy
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of Oral Milk Immunotherapy for Cow's Milk Allergy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Milk Hypersensitivity
Keywords: Food Allergy
Oral Immunotherapy
Immunoglobulin E
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Duke University
First posted: 2007-04-25
Enrollment: 20
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: This is a prospective, multi-center, clinical trial involving children aged 6 to 21 years with persistent cow's milk allergy. These children will be recruited from 2 sites (Johns Hopkins and Duke University) and will undergo initial screening and double-blind, placebo-controlled, food challenge (DBPCFC) to confirm threshold dose for reactivity to milk. Patients will be treated with milk oral immunotherapy (OIT) or placebo for 22-30 weeks. Those who reach an adequate maintenance dose for OIT will undergo a second DBPCFC. Those who develop desensitization will continue with daily milk intake and undergo a third DBPCFC. Those in the treatment group who are not desensitized will return to strict avoidance. Those in placebo group will be offered to begin treatment or continue with strict milk avoidance. Symptom and diet information will be collected initially and at regular intervals. Bloodwork, skin prick tests (SPTs), pulmonary function tests (PFTs), and oral secretion samples will be done initially and at periodic intervals.

Eligibility criteria: Inclusion Criteria:

* Provide signed informed consent (by parent or legal guardian if the subject is a minor) and informed assent if applicable
* Age 6 to 21 years
* Must have history of symptomatic reactivity to cow's milk (eczema, urticaria, upper/lower resp., GI, other associated rash, oral symptoms)
* History of positive skin prick test (wheal \>/= histamine control) or milk-Immunoglobulin E (IgE)\>0.35 kilounits per liter (kU/L)
* Positive DBPCFC
* All females of child bearing age must be using appropriate birth control

Exclusion Criteria:

* History of anaphylaxis requiring hospitalization
* History of intubation related to asthma
* Has the ability to tolerate \>2.4gram of milk protein at initial DBPCFC
* Has a history of allergy to any component of vehicle
* Pregnancy (need negative test)
* Viral upper respiratory infection (URI) or gastroenteritis within 7days of OFC (OFC needs to be rescheduled)
* Has pulmonary function tests \<80% of predicted (FEV1) or clinical history consistent with moderate persistent asthma
* Currently taking greater than medium dose inhaled corticosteroid (\>400mcg/day fluticasone or fluticasone equivalent if \</=12yo or \>600mcg/day if \>12 years old)
* Antihistamine within 1 week prior to skin testing or food challenges (Skin testing and/or food challenge needs to be rescheduled)
* Systemic corticosteroid within 4 weeks prior to baseline visit
* Receiving omalizumab, beta-blocker, Angiotensin-converting enzyme (ACE) inhibitor or tricyclic antidepressant therapy
* Chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy (e.g., heart disease, diabetes)
* Participation in any interventional study for treatment of a food allergy in the past 12 months
* Severe reaction at initial DBPCFC, defined as:

  i. Life-threatening anaphylaxis ii. Requires overnight hospitalization

Primary outcomes:
measure: The Median Milk Threshold Dose Inducing a Reaction
timeFrame: Baseline and 23 weeks
Secondary outcomes:
measure: Changes in Cow Milk-IgE
timeFrame: Baseline and 23 weeks
measure: Changes in Cow Milk Immunoglobulin G4 (IgG4)
timeFrame: Baseline and 23 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Johns Hopkins University
name: Robert A Wood, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Buchanan AD, Green TD, Jones SM, Scurlock AM, Christie L, Althage KA, Steele PH, Pons L, Helm RM, Lee LA, Burks AW. Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol. 2007 Jan;119(1):199-205. doi: 10.1016/j.jaci.2006.09.016. Epub 2006 Oct 27.
citation: Meglio P, Bartone E, Plantamura M, Arabito E, Giampietro PG. A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy. 2004 Sep;59(9):980-7. doi: 10.1111/j.1398-9995.2004.00542.x.
citation: Enrique E, Pineda F, Malek T, Bartra J, Basagana M, Tella R, Castello JV, Alonso R, de Mateo JA, Cerda-Trias T, San Miguel-Moncin Mdel M, Monzon S, Garcia M, Palacios R, Cistero-Bahima A. Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol. 2005 Nov;116(5):1073-9. doi: 10.1016/j.jaci.2005.08.027. Epub 2005 Oct 3.
citation: Skripak JM, Nash SD, Rowley H, Brereton NH, Oh S, Hamilton RG, Matsui EC, Burks AW, Wood RA. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008 Dec;122(6):1154-60. doi: 10.1016/j.jaci.2008.09.030. Epub 2008 Oct 25.