Clinical trial NCT00932828: Determining the Efficacy and Value of Immunotherapy on the Likelihood of Peanut Tolerance: The DEVIL Study
Official title: Determining the Efficacy and Value of Immunotherapy on the Likelihood of Peanut Tolerance: The DEVIL Study; Grant "Optimizing Tolerance Induction in Peanut Allergy: The DEVIL Study"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Food Hypersensitivity
Keywords: Peanut allergy
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2009-07-03
Enrollment: 37
Sex: ALL
Minimum age (years): 9
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: For the purposes of the primary outcome, all subjects will receive peanut OIT and represent a single group. For exploratory analysis, subjects will be randomized to high and low dose OIT to potentially look for a dose response.
Primary purpose: TREATMENT

Brief summary: Peanut allergy is known to cause severe anaphylactic reactions.The goal of this proposal is to produce a new treatment that would benefit young subjects who have recently been diagnosed with peanut allergy by lowering the risk of anaphylactic reactions (desensitization), and changing the peanut-specific immune response in subjects who have peanut allergy (tolerance).

Detailed description: Peanut allergy is known to cause severe anaphylactic reactions. Compared with other food allergies, it tends to be more persistent and its prevalence seems to be rising. Currently, there is no proven treatment other than strict avoidance. We are attempting to decrease the risk of anaphylaxis on accidental ingestion by desensitizing subjects to peanut using peanut mucosal immunotherapy (PMIT) more commonly called oral immunotherapy (OIT). We are also studying the effect of PMIT on the peanut-specific immune response to determine if tolerance to peanut protein will develop. Based on our preliminary work and recent studies supporting the importance of early oral exposure in tolerance induction, we propose that early treatment of peanut allergy with PMIT will be safe and effective. Children ages 9 to 36 months with peanut allergy will be randomized to receive high or low dose PMIT using peanut flour. Subjects will undergo desensitization on the first day and then increase the doses gradually to a maintenance dose. Doses will be taken daily at home except for dose increases which will be done on the research unit. Subjects will undergo a double-blinded, placebo-controlled food challenge (DBPCFC) if challenge criteria are met. Subjects passing the first challenge will stop PMIT and repeat the DBPCFC to assess tolerance. Outcome variables of interest include response to oral food challenges (OFC), skin prick testing, peanut specific serum immunoglobin E (IgE), immunoglobin G (IgG), and immunoglobin G4 (IgG4) and stool immunoglobin A (IgA), T and B cell responses, quality of life, and adverse events. As secondary and exploratory outcomes, these longitudinal results will be compared between high and low dose PMIT groups and controls using appropriate statistical analysis.

Eligibility criteria: Inclusion Criteria:

* Age 9-36 months of either sex, any race, any ethnicity at the time of the initial visit
* EITHER a positive skin prick test to peanuts or in vitro \[CAP-FEIA\] peanut immunoglobin E (IgE) level in the blood \> 0.35 kU/L PLUS a history of a clinical allergic reaction (defined as significant clinical symptoms occurring within 60 minutes after ingesting peanuts) within 6 months of screening
* OR a positive prick skin test to peanuts and in vitro \[CAP-FEIA\] peanut IgE level \> 5 kU/L when there is no history of allergic reaction and no known peanut exposure
* Provision of signed informed consent
* Development of symptoms characteristic of IgE-mediated food allergy (urticaria, angioedema, respiratory distress/wheeze/cough, vomiting/diarrhea, anaphylaxis) during initial oral food challenge

Exclusion Criteria:

* History of severe anaphylaxis to peanut as defined by hypoxia, hypotension, or neurological compromise
* Currently participating in a study using an investigational new drug
* Participation in any interventional study for the treatment of food allergy in the past 12 months
* Subjects with a known wheat food allergy will be excluded because of cross contamination of oat with wheat
* Severe atopic dermatitis
* Currently being treated with greater than medium daily doses of inhaled corticosteroids, as defined by the National Heart Lung and Blood Institute (NHLBI) guidelines
* Inability to discontinue antihistamines for skin testing and OFCs

Primary outcomes:
measure: Determine the Percentage of Subjects Who Demonstrate Sustained Unresponsiveness (SU) by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC).
timeFrame: After 36 months of OIT dosing followed by 1 month of avoidance
Secondary outcomes:
measure: Determine the Percentage of Subjects Who Demonstrate Desensitization by a Negative Double-blind Placebo-controlled Food Challenge (DBPCFC).
timeFrame: After 36 months of OIT dosing
measure: Determine the Frequency of Treatment-related Adverse Effects (TAE) From Peanut OIT.
timeFrame: After 36 months of OIT dosing followed by 1 month of avoidance
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
Study officials:
affiliation: University of North Carolina
name: Arvil W Burks, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vickery BP, Berglund JP, Burk CM, Fine JP, Kim EH, Kim JI, Keet CA, Kulis M, Orgel KG, Guo R, Steele PH, Virkud YV, Ye P, Wright BL, Wood RA, Burks AW. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. J Allergy Clin Immunol. 2017 Jan;139(1):173-181.e8. doi: 10.1016/j.jaci.2016.05.027. Epub 2016 Aug 10.