Oral Immunotherapy for Peanut Allergy (PMIT)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if mucosal peanut immunotherapy will make subjects who have peanut allergy less allergic and induce changes in their immune system.

Detailed Description
-----------------
Peanut allergy is known to cause severe anaphylactic reactions. Compared with other food allergies it tends to be more persistent and also 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 oral mucosal immunotherapy (OIT). We are also studying the effect of peanut OIT on the peanut specific immune response to determine if tolerance to peanut protein will develop. Children ages 1 to 18 with peanut allergy will be randomized to peanut OIT or placebo. Subjects will undergo a modified rush immunotherapy on the first day and then increase the doses at least every two weeks up to a maintenance dose of 4 grams (equivalent to about 13 peanuts). Doses will be taken daily at home except for dose increases which will be done on the research unit. Subjects will undergo a double-blind, placebo-controlled food challenge (DBPCFC) after 12 months and then be unblinded. Placebo subjects will cross over to open-label peanut OIT and undergo an identical buildup schedule up to 12 months. All subjects will then complete at least 36 months of peanut OIT therapy after which once skin prick (<5 mm) and IgE (<15 kU/L) criteria are met, they will then complete the end of study DBPCFC. Dosing will continue up to a maximum of 60 months after which even if criteria are not met, the subject will undergo the end of study DBPCFC. Outcome variables of interest include response to DBPCFC, skin prick testing, peanut specific IgE, and adverse events. These results will be compared between the start and end of peanut OIT using appropriate statistical analysis.

Official Title
-----------------
Oral Immunotherapy for Peanut Allergy (2nd Generation PMIT Collaboration With Arkansas Children's)

Conditions
-----------------
Food Hypersensitivity

Intervention / Treatment
-----------------
* Biological: Peanut OIT
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject between 1 and 18 years of age EITHER history of significant clinical symptoms occurring within 60 minutes after ingesting peanuts greater than 6 months ago AND peanut specific IgE >15 kU/L OR history of significant clinical symptoms occurring within 60 minutes after ingesting peanuts within the past 6 months AND peanut specific IgE > 7 kU/L A family that will be able to be compliant with all study visits All females of child bearing age must be using appropriate birth control Exclusion Criteria: Subjects with a history of severe, anaphylaxis to peanut Medical history that would prevent a double blind placebo controlled oral food challenge (DBPCFC/OFC) to peanut Unable to cooperate with challenge procedures or unable to be reached by telephone for follow-up Diagnosed oat allergy Pregnancy or lactation

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Oat flour ingested daily as a placebo | Biological: Placebo<br>* Oat flour matched by weight and consistency that is ingested daily as a placebo<br>|
| Active Comparator: Peanut OIT<br>Peanut flour ingested daily as oral mucosal immunotherapy | Biological: Peanut OIT<br>* Defatted peanut flour ingested daily as oral mucosal immunotherapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Amount of Peanut Protein Ingested Before An Allergic Reaction is Observed During the Double-blind, Placebo Controlled Food Challenge (DBPCFC) After Completing Treatment With Peanut OIT. | After completing the peanut OIT protocol (defined as treatment with peanut OIT for at least 36-months AND a peanut-specific IgE >2 and <15 AND skin prick test is <5 mm OR a maximum of 60 months of treatment), the reaction threshold for subjects is assessed by a DBPCFC. This involves eating small increasing doses of peanut protein in a blinded fashion up to a cumulative total of 5000 mg. An identical food challenge is also performed with oat flour as a placebo. The cumulative amount of peanut protein ingested prior to the dose that causes a reaction requiring treatment is reported as the reaction threshold. | 36-60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Amount of Peanut Protein Ingested Before An Allergic Reaction is Observed During the Double-blind, Placebo Controlled Food Challenge (DBPCFC) After Completing 12 Months of Blinded Peanut OIT or Placebo Treatment. | After 12 months of blinded Peanut OIT treatment, the reaction threshold for subjects is assessed by a DBPCFC. This involves eating small increasing doses of peanut protein in a blinded fashion up to a cumulative total of 4710 mg. An identical food challenge is also performed with oat flour as a placebo. The cumulative amount of peanut protein ingested prior to the dose that causes a reaction requiring treatment is reported as the reaction threshold. | 12 months | 
| The Change From Baseline Through the End of Peanut OIT Treatment in Wheal Size Diameter Following Peanut Skin Prick Testing | Skin prick testing is performed by scratching the skin with a small amount of peanut and observing for redness and a raised bump called a wheal. The diameter of the wheal is measured with a ruler in mm and recorded as a measure of peanut-specific IgE and mast cell reactivity in an allergic subject. A decrease in wheal size after treatment would represent suppression of the allergic response. | Baseline to end of open label phase treatment (36-60 months) | 
| The Change From Baseline Through the End of Peanut OIT Treatment in Peanut-specific IgE in the Blood | Peanut specific IgE on the surface of mast cells and basophils releases histamine when exposed to peanut causing symptoms of allergy. Free-floating peanut-specific IgE is measured from serum in the blood by an immunoCAP machine and reported in kU/L. A lower level of peanut-specific IgE could suggest a decrease in the probability of reaction for a subject who is exposed to peanut. | Baseline to end of open label phase treatment (36-60 months) | 
| The Change From Baseline Through the End of Peanut OIT Treatment in Peanut-specific IgG4 in the Blood. | Peanut specific IgG4 is thought to have a protective effect for a subject when exposed to peanut possibly by interfering with IgE. Peanut-specific IgG4 is measured from serum in the blood by an immunoCAP machine and reported in mg/dL. A higher level of peanut-specific IgG4 could suggest a decrease in the probability of reaction for a subject who is exposed to peanut. | Baseline to end of open label phase treatment (36-60 months) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Peanut allergy