Determining the Efficacy and Value of Immunotherapy on the Likelihood of Peanut Tolerance: The DEVIL Study

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.

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